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Wuji Wan (WJW) is a traditional Chinese medicine formula that can be found in the "Prescriptions of Taiping Benevolent Dispensary" that has been employed in treating gastric discomfort, burning epigastric pain, and gastric reflux for hundreds of years and has shown promise for treating gastric ulcers (GUs). However, the active components and mechanism of action against GUs remain unclear. The aim of this study was to explore the active components of WJW and elucidate the underlying mechanism involved in treating GUs. Initially, cell viability was measured by a cell counting kit 8 (CCK-8) assay to evaluate the efficacy of WJW-containing serum in vitro. The gastric ulcer index, ulcer inhibition rate, hematoxylin and staining (H&E), and periodic acid-Schiff (PAS) staining were used to evaluate the therapeutic effect of WJW in vivo. Subsequently, the levels of inflammatory factors and oxidative stress factors were determined using an enzyme-linked immunosorbent assays (ELISA) on in vitro and in vivo samples. Additionally, UPLC-Q Exactive Plus Orbitrap HRMS was used to analyze the components that were absorbed into the blood of WJW and its metabolites. Network pharmacology and metabolomics were subsequently used to identify the targets and pathways. Real-time quantitative PCR (RT‒qPCR) and Western blotting were used to verify the mRNA and protein levels of the key targets and pathways. Finally, the active components were identified by molecular docking to verify the binding stability of the components and key targets. WJW-containing serum ameliorated ethanol-induced damage in GES-1 cells and promoted cell healing. WJW-containing serum reduced IL-6, TNF-α, MDA, and LDH levels while increasing IL-10, SOD, and T-AOC levels in the cells. Moreover, WJW treatment resulted in decreased IL-6, TNF-α, and MDA levels and increased IL-10, SOD, PGE 2, and NO levels in GUs rats. In addition, eight components of WJW were absorbed into the blood. The network pharmacology results revealed 192 common targets for blood entry components and GUs, and KEGG analysis revealed that apoptosis signaling pathways were the main pathways involved in WJW activity against GUs. Metabolomic screening was used to identify 13 differential metabolites. There were 23 common targets for blood entry components, GUs, and differential metabolites, with the key targets TNF (TNF-α), AKT1, PTGS2 (COX2) and MAPK1. WJW significantly inhibited the expression of Bax, Caspase-9, Caspase-3, cleaved Caspase-9, cleaved Caspase-3, TNF-α, COX2, and p-p44/42 MAPK while promoting the expression of Bcl-2 and p-AKT1. Molecular docking revealed that the active components of WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. WJW treatment reduces inflammation and oxidative stress injury and inhibits apoptosis signaling pathways. The main active components are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. In this paper, we provide a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms. [Display omitted] • WJW treatment GUs potential mechanism is by inhibiting inflammation, oxidative stress injury and apoptosis signaling pathways. • Integrated network pharmacology and metabolomics identified the key targets of WJW in the treatment of GUs, namely TNF, AKT1, PTGS2 and MAPK1. • The active components in WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. • This paper provides a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms. [ABSTRACT FROM AUTHOR]

Sporisorium reilianum f. sp. reilianum (SSR) is a fungus isolated from a medicinal plant. Recorded in the "Compilation of National Chinese Herbal Medicine" and "Compendium of Materia Medica," it was used for preventing and treating intestinal diseases, enhancing immune function, etc. In this study, we investigated the chemical composition and bioactivity of SSR. Network pharmacology is utilized for predictive analysis and targeting pathway studies of anti-inflammatory bowel disease (IBD) mechanisms. Pharmacological activity against enteritis is evaluated using zebrafish (Danio rerio) as model animals. To reveal the treatment of IBD by SSR used as traditional medicine and food, based on molecular biology identification of SSR firstly, and the pharmaceutical components & its toxicities, biological activity & mechanism of SSR were explored. Using chromatography and zebrafish IBD model induced by dextran sulfate sodium (DSS), nine compounds were first identified by nuclear magnetic resonance (NMR). The toxicity of ethanol crude extract and monomers from SSR were evaluated by evaluating the phenotypic characteristics of zebrafish embryos and larvae, histomorphology and pathology of the zebrafish model guided by network pharmacology were conducted. The zebrafish embryo development did not show toxicity. The molecular docking and enrichment pathway results predicted that metabolites 3 & 4 (N-trans- feruloyl-3-methoxytyramine & N-cis- feruloyl-3-methoxytyramine) and 7 & 8 (4- N- trans -p-coumaroyltyramine & 4- N-cis --p-coumaroyltyramine) have anti-enteritis activities. This paper lays an experimental foundation for developing new drugs and functional foods. [Display omitted] • The basal source of the fungi was identified firstly. • The nine compounds were firstly isolated and characterized fully. • The mechanisms of anti-IBD was explored by the network pharmacology. • Zebrafish IBD Model was established to explore the anti-IBD effect of Sporisorium reilianum f. sp. reilianum for the first time. • Histomorphology and pathology were conducted. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aconitum has been used as local and traditional medicines in many asian regions for the treatment of various diseases such as collapse, syncope, painful joints, oedema, bronchial asthma et al. Higenamine, a plant-based alkaloid, was initially isolated from Aconitum and identified as the active cardiotonic component of Aconitum . It has been tested as a candidate of pharmacologic stress agent in the detection of coronary artery diseases (CADs) and now researchers have just accomplished the phase III clinical studies successfully in China. Besides, a large number of studies have revealed the various pharmacological properties and potentially multi-spectral medical applications of higenamine. However, to date, no comprehensive review on higenamine has been published. Aim of the review This present paper aims to compile a comprehensive update regarding the biochemistry, pharmacokinetic features, pharmacological activities, clinical and potential clinical uses and toxicities on higenamine with the ultimate objective of providing a guide for future research on this drug. Materials and methods The selection of relevant data was made through a search using the keyword “higenamine” in “Web of science”, “Pubmed”, and “China Knowledge Resource Integrated (CNKI)”. Information was also acquired from local classic herbal literature, government reports and conference papers. Results In addition to Aconitum , higenamine also exists in many other plants including Tinospora crispa , Nandina domestica T HUNBERG , Gnetum Parvifolium C.Y. Cheng, sarum Heterotropoides , Nelumbo nucifera , N.nucifera . The pharmacokinetic studies conducted in animals and humans showed that higenamine conformed to a two-compartment pharmacokinetic model. Studies over the last four decades on higenamine have revealed its various pharmacological properties such as positive inotropic and chronotropic effect, activating slow channel effect, vascular and tracheal relaxation effect, anti-thrombotic, anti-apoptotic and anti-oxidative effect, anti-inflammatory and immunomodulatory effect. This phytochemical constituent has shown its potential therapeutic effects for diseases like heart failure, disseminated intravascular coagulation (DIC), shock, arthritis, asthma, ischemia/reperfusion (I/R) injuries and erectile dysfunction. Conclusions Extensive basic and clinical studies on higenamine showed valuable therapeutic effects on different disorders. However, the underlying mechanisms of higenamine have not been established. Therefore, the safety, tolerability and efficacy of higenamine are as yet, not fully understood. Additionally, some of the studies were small sample-sized and unreliable. To sum up, there is a need for deeper investigation in the mechanisms of higenamine action, as well as well-designed preclinical and clinical trials studies to test the safety and clinical value of the drug. [ABSTRACT FROM AUTHOR]

Sophora flavescens Ait.- Angelica sinensis (Oliv.) Diels drug pairing (SA) is a transformed drug pairing from Shengui pill, a traditional Chinese medicine prescription in the ninth volume of Traditional Chinese Medicine classic "Gu Jin Yi Jian", which is famous for clearing heat, moistening dryness, and promoting blood circulation. It is commonly used in the treatment of eczema, a skin condition that causes itching and inflammation. Despite its widespread use, there is still limited research on the mechanism of how SA treats eczema. This paper aims to fill this gap by conducting animal experiments to uncover the mechanism behind SA's therapeutic effects on eczema. Our findings provide a solid foundation for the clinical use of this TCM prescription. The basic purpose of this study is to clarify the therapeutic mechanism of Sophora flavescens-Angelica sinensis (SA) in the treatment and control of eczema. The chemical compositions of SA were analyzed using HPLC-Q-Orbitrap-MS. In vivo, a mouse model of eczema was created, and the serum levels of TNF-α and IL-1β were quantified using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was performed to assess the pathological state of the mouse skin, and immunohistochemical technique (IHC) was employed to estimate the contents of TNF-α, TLR4, and NF-κB semi-quantitatively. The expression levels of TLR4, MyD88, and NF-κB mRNA were determined through real-time quantitative polymerase chain reaction (qRT-PCR). Western Blotting was utilized to identify the protein levels of TLR4, MyD88, and NF-κB in mouse skin tissue. SA identified 18 active chemicals, some of which were shown in vivo to inhibit the TLR4/MyD88/NF-κB signaling pathway while reducing serum levels of TNF-α and IL-1β, making them ideal agents for the treatment of eczema. SA's anti-inflammatory properties are attributed to its ability to reduce serum levels of TNF-α and IL-1β, likewise inhibit the TLR4/MyD88/NF-κB signaling pathway. [Display omitted] • Application of SG in the treatment of acute eczema. • Study on the mechanism of SG in the treatment of acute eczema for the first time. • The experiments were carried out in vivo. • The results showed that SG could reduce the expression of IL-1β and TNF-α. • The anti-inflammation effect of SG is mediated by TLR4/MyD88/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

Cholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. The aim of this paper was to investigate the potential protective mechanism of CuB against CLI. First, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. A total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. By combining network pharmacology with in vivo and i n vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI. [Display omitted] • Targets of CuB treatment for cholestasis are enriched in the inflammatory pathway. • STAT3 and HIF-1α are key targets. • CuB alleviates cholestasis-induced liver damage and inflammatory reactions. • CuB prevents cholestasis by inhibiting the IL-6/STAT3/HIF-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Erigeron breviscapus is a common medicine of eight ethnic minorities, including Miao, Naxi, and Yi. As early as the Ming Dynasty (AD 1368–1644), Lanmao's Materia Medica of Southern Yunnan (AD 1436) recorded that the medicine is used for the treatment of "Zuo tan you huan." In modern pharmacological research, Erigeron breviscapus injection is the most commonly used preparation in the treatment of ischemic stroke caused by acute cerebral infarction, but its mechanism of action in the treatment of ischemic stroke is not well understood. In this study, a metabonomics study based on ultraperformance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was used in investigating the effect of a traditional Chinese medicine preparation Erigeron breviscapus injection on the rat model of focal cerebral ischemia-reperfusion and the affinity of its main components with the targets of mitochondrial apoptotic pathways. This study used molecular docking technology to verify the effective binding ability of main effective components of Erigeron breviscapus injection to target proteins related to mitochondrial apoptosis pathway. This study developed a metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of focal cerebral ischemia-reperfusion model group and healthy control group was achieved. Erigeron breviscapus injection can significantly reduce the area of cerebral infarction, improve tissue morphological lesion in rats, and can increase the number of Nissl bodies. It may be a promoting factor by inhibiting hippocampal nerve cell apoptosis and Bax protein expression and by exerting effects against ischemia reperfusion after the induction of apoptosis. Thus, it plays a role in brain protection. Moreover, it can considerably promote the recovery of neurological deficiency signs in advance. Meanwhile, Erigeron breviscapus decreased malondialdehyde content and T-NOS activity. Its curative effect from strong to weak order: low dose > high dose > medium dose. The representative components of Erigeron breviscapus have good affinity with the active sites of mitochondrial apoptosis-related proteins. Metabolomics found that the potential biomarkers regulated by breviscapine are kynurequinolinic acid, succinylornithine, and leucine proline. It is speculated that it may participate in TRP–kynurequinolinic acid and succinylornithine–urea cycle–NO metabolic pathways. This paper revealed the potential biomarkers and metabolic pathways regulated by Erigeron breviscapus. It was speculated that the mechanism is related to its inhibition of mitochondrion-mediated apoptosis. Erigeron breviscapus could restore the metabolic profiles of the model animals to normal animal levels. The mechanism may be related to the potential biomarkers of quinolinic acid, succinylornithine, and leucine proline and the metabolic pathways involved. However, the exact mechanism by which Erigeron breviscapus inhibits mitochondrion-mediated apoptosis remains to be further explored. [Display omitted] • The metabolic profile of cerebral ischemia-reperfusion injury model rats regulated by Breviscapus injection were revealed. • A new method of metabolomics combined with pharmacodynamics to evaluate the effectiveness of ethnomedicine was explored. • Erigeron breviscapus has high research value. • Erigeron breviscapus is a common medicine of eight ethnic minorities, such as the Miao, Naxi and Yi nationalities. [ABSTRACT FROM AUTHOR]

Qilong capsule (QLC) is a compound traditional Chinese medicine commonly used to treat ischemic stroke (IS). QLC is made of eight kinds of medicinal materials. It has two kinds of monarch medicine and six kinds of minister medicine. However, the pharmacodynamic mechanism of QLC is still unknown. The aim of this paper was to evaluate the pharmacology mechanism of QLC against ischemic stroke through coagulation, inflammation and apoptosis. We used an existing zebrafish model to explore the protective mechanism of QLC on IS. We treated normally-developing zebrafish larvae with QLC and ponatinib 2 days post fertilization (dpf), and used the area of cerebral vascular thrombosis, red blood cell staining intensity, and brain cell apoptosis to quantitate QLC efficacy against IS. Evaluation of brain inflammation in zebrafish by observing macrophage aggregation and migration. In addition, we also explored the effect of QLC on zebrafish angiogenesis. Quantitative polymerase chain reaction (qPCR) was used to detect changes in the expression of genes involved in coagulation, inflammation, vascular endothelium, and apoptosis. We found that QLC reduced the area affected by ponatinib-induced cerebral vascular embolism, erythrocyte staining intensity, and the number of apoptotic brain cells. For inflammation, QLC can improve the aggregation and migration of macrophages. QLC can significantly promote the formation of blood vessels in zebrafish. qPCR showed that QLC inhibited the expression of genes related to coagulation, inflammation, and apoptosis. Qilong capsule had a significant protective efficacy in ponatinib-induced IS. [Display omitted] • We employ a zebrafish ischemic stroke model that allows rapid drug screening. • Qilong capsule protects against ischemic stroke by regulating coagulation, inflammation and apoptosis. • Qilong capsule can promote the growth of blood vessels in zebrafish. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Da-Huang-Fu-Zi-Tang (DHFZT) is a crucial TCM formula commonly used for the treatment of acute pancreatitis in Chinese clinical application. Our previous work found that DHFZT could act against pancreatic injury in rats with severe acute pancreatitis (SAP). The goal of this paper was to study the underlying correlations between the chemical spectra and the protective effect of DHFZT on pancreatic acinar cell to reveal the real bioactive compounds in DHFZT. Materials and methods: The fingerprint chromatograms of rat serum after oral administration of DHFZT were established by UHPLC-ESI-Q-TOF-MS technique. At the same time, the model of anti-acute pancreatitis on cells was established by adding 10?7 mol/L cerulein to AR42J cell line, and the protective effects of the serum on pancreatic acinar cell from injury was evaluated by detecting the efficacy of amylase. Then, the spectrum–effect relationships between UHPLC fingerprints and anti-acute pancreatitis activities were evaluated using canonical correlation analysis (CCA) statistical method. The chromatogram separation was performed on a C18 reversed phase UHPLC column (2.1mm×100mm, 3.5?m, Agilent), the column temperature was set at 35°C. The mobile phase consisted of 0.1% formic acid and acetonitrile with gradient elution. The serum samples were analyzed both in negative and positive ion mode. The mother and productive ions were scanned within the mass range of m/z 100–1200 and 50–1200, respectively. A thorough analysis of a great deal of information of the constituents in the rat serum was undertaken. The structure identification of the detected compounds was achieved by using high resolution MS values as well as the MS/MS fragments. Results: Eighteen peaks in rat serum after oral administration of DHFZT were detected within only 30min recorded chromatograms. The structure of the 18 compounds were then given out, of which 10 were the original form of compounds absorbed from DHFZT, 8 were the metabolites of the compounds existed in rat serum. According to the CCA results, talatisamine, rhein glucoside, rhein isomer methylation, hypaconine, hydroxyl-chrysophanol, emodin glucuronide conjugation, and chrysophanol glucuronide conjugation were finally found to be the main anti-acute pancreatitis components in DHFZT. Conclusions: The model presented in this paper successfully discovered the spectrum–effect relationships of DHFZT, which showed a representative way to discover the primary active ingredients from the complicated herbal drugs. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Chinese traditional medicine Rhizoma drynariae (Gusuibu) is widely used for clinically treating osteoporosis and bone non-union. Naringin and its active metabolite naringenin are the main active ingredients of Rhizoma drynariae total flavonoids. Aim of the study: The purpose of this paper is to confirm estrogenic and anti-estrogenic activity of naringin and naringenin, and provide the basic data to further study for the dose–effect relationship and the mechanism for Rhizoma drynariae in treatment of osteoporosis and other estrogen deficiency-related diseases. Materials and methods: Naringin was extracted from Rhizoma drynariae. Naringin and its metabolin naringenin were tested estrogenic and anti-estrogenic activities through the experiment of cell proliferation and uterus weight gain in mice. Their estrogen-receptor binding abilities were tested by yeast two-hybrid experiment and nuclear receptor cofactor assays (RCAS) experiment, and their possible binding sites for ERβ were performed by computer aided molecular docking technology. Results: Naringin and naringenin showed significant effects on the proliferation of estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen. Induction increased proliferation as the drug concentration, and the strongest proliferation appeared at a concentration of 8.6×10−5 M. When estradiol (10−10 M) and the different concentrations of naringin or naringenin were treated at the same time, naringin and naringenin could result in antagonistic effects on estradiol-induced MCF-7 cell proliferation, but they did not significantly affect proliferation of estrogen-insensitive ER(−) MDA-MB-231 cells. Naringin and naringenin exhibited higher binding capacity to estrogen receptor β (ERβ) than estrogen receptor α (ERα) in yeast two-hybrid experiments and nuclear receptor cofactor assays (RCAS) experiment. Docking simulation between naringin/naringenin and ERβ were performed, and the corresponding binding free energies of naringin–receptor and naringenin–receptor docked complexes were −7.95 and −10.45kcal/mol. Hydrogen bonds were found between naringin and the amino acid residues Lys304 and His308. The oxygen atom (O11) of naringenin formed hydrogen bond to Arg346, and there may be hydrophobic space interactions between phenyl group (C13–C18) of naringenin and the amino acid residues Leu298, Met336, Met340, Phe356, Ile376 and Leu380. Conclusions: Naringin and naringenin revealed a double directional adjusting function of estrogenic and anti-estrogenic activities. Both of them showed estrogenic agonist activity at low concentration or lack of endogenous estrogen. On the other hand, they also acted as estrogenic antagonists at high concentrations or too much endogenous estrogen. They produced estrogenic and anti-estrogenic effects primarily through selectively binding with ERβ, which could prevent and treat osteoporosis with the mechanism of estrogenic receptor agitation. This paper confirmed the estrogenic and anti-estrogenic activity of naringin and naringenin, and further studies were still essential to study their dose–effect relationship and the anti-osteoporosis mechanism for Rhizoma drynariae in the treatment of osteoporosis and other estrogen deficiency-related diseases. [Copyright &y& Elsevier]

Rhus chinensis Mill. is a species of the genus Rhus belonging to the family Anacardiaceae. Its fruits used to treat/prevent liver related diseases (e.g., jaundice and hepatitis) in folk medicine. Otherwise, the effects and underlying mechanisms of the fruits on the prevention of isoniazid and rifampicin-caused liver injury have not been investigated. To study the preventive effects and mechanisms of the Rhus chinensis Mill. fruits on isoniazid and rifampicin-caused liver injury. This experiment was based on rifampicin (75 mg/kg/day) and isoniazid (75 mg/kg/day)-induced liver damage model to explain the pharmacological effects of Rhus chinensis Mill. fruits. The prevention of the extract from Rhus chinensis Mill. fruits on isoniazid and rifampicin-caused liver injury were evaluated using biochemical parameters, histopathological analysis, and immunofluorescence technique. Apart from that, the potential molecular mechanisms were elucidated by analyzing the expression of such crucial proteins participated in oxidative stress, apoptosis, and bile acid transport. The extract from Rhus chinensis Mill. fruits significantly reduced the levels of ALT, AST, TBIL, ALP and MDA. Besides, the extract, especially 800 mg/kg b.w., was remarkably decreased the content of TNF-α,IL-6 and IL-1β, restored the levels of GSH and SOD. The results of Western blot also presented that the extract could activate the Nrf2 protein pathway and inhibit the expression of CYP2E1 to reduce oxidative stress. Meanwhile, the extract significantly up-regulated the expressions of BSEP and Mrp2 to regulate the transport of bile acid, and alleviated the cellular apoptosis via adjusting the expression of Bax and Bcl-2 proteins. Rhus chinensis Mill. fruits can prevent the liver injury induced by isoniazid and rifampicin in mice through adjusting the expressions of multiple proteins in oxidative stress, apoptosis, and bile acid transport pathways. This paper may provide scientific basis for the fruits as a Chinese medicine to prevent/cure liver injury. [Display omitted] • R. chinensis fruits were rich in polyphenols, especially quercetin and gallic acid. • The fruits effectively prevented liver injury induced by anti-tuberculosis drugs. • The fruits improved oxidative stress via Nrf2 signaling pathway & CYP2E1 protein. • Hepatocyte apoptosis was prevented by the fruits adjusting Bax and Bcl-2 proteins. • Bile acid transport was obviously ameliorated via up-grading BSEP and Mrp2 expression. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a central nervous system disease that causes severe disability or death. Even though Annao Pingchong decoction (ANPCD), a traditional Chinese decoction, has been used clinically to treat ICH in China, its molecular mechanism remains unclear. To study whether the neuroprotective effect of ANPCD on ICH rats is achieved by alleviating neuroinflammation. This paper mainly explored whether inflammation-related signaling pathways (HMGB1/TLR4/NF-κB P65) plays a role in ANPCD treatment of ICH rats. Liquid chromatography-tandem mass spectrometry was used to analyze the chemical composition of ANPCD. ICH models were established by injecting autologous whole blood into the left caudate nucleus of Sprague-Dawley (SD) rats. Modified neurological severity scoring (mNSS) was used to assess the neurological deficits. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA). Pathological changes in the rat brains were observed using hematoxylin-eosin, Nissl, and TUNEL staining. The protein levels of HMGB1, TLR4, NF-κB p65, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were measured by western blotting and immunofluorescence analysis. Ninety-three ANPCD compounds were identified, including 48 active plasma components. Treatment with ANPCD effectively improved the outcome, as observed by the neurological function scores analysis and brain histopathology. Our results showed that ANPCD exerts its anti-inflammatory effects by significantly downregulating the expression of HMGB1, TLR4, NF-κB p65, TNF-α, IL-1β, and IL-6. ANPCD also exerted anti-apoptotic effects by significantly decreasing the apoptosis rate and Bax/Bcl-2 ratio. We found that ANPCD had neuroprotective effect in clinical work. Here, we also found that the action mechanism of ANPCD might be related to attenuate neuroinflammation and apoptosis. These effects were achieved by inhibiting the expression of HMGB1, TLR4 and NF-κB p65. [Display omitted] • ANPCD can alleviate the neurological impairment after ICH in Rats. • ANPCD can attenuate neuroinflammation and apoptosis. • ANPCD can decrease the expression of HMGB1, TLR4 and NF-κB p65. [ABSTRACT FROM AUTHOR]

Dahuang Zhechong pill (DHZCP), a traditional Chinese medicine, was derived from the famous book Unk " Synopsis of Prescriptions of the Golden Chamber " during the Han dynasty. Owing to its ability to invigorate the circulation of blood in Chinese medicine, DHZCP is usually used for treating liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Clinical application have shown that DHZCP exhibits satisfactory therapeutic effects in HCC adjuvant therapy; however, little is known about its underlying mechanisms. We aimed to clarify the mechanism of DHZCP against hepatic sinusoidal capillarization in rats with LC and HCC by inhibiting the MK/integrin signaling pathway of liver sinusoidal endothelial cells (LSECs). The contents of 29 characteristic components in DHZCP were determined by ultraperformance liquid chromatography-tandem mass spectrometry. DEN (Diethylnitrosamine)-induced LC and HCC rat models were constructed, and DHZCP was administered when the disease entered the LC stage. After 4 or 12 weeks of administration, hematoxylin and eosin staining, Masson staining, Metavir score, and SSCP (Single strand conformation polymorphism) gene mutation detection were used to confirm tissue fibrosis and cancer. The levels of NO, ET-1 and TXA2, which can regulate vasomotor functions and activate the MK/Itgα6/Src signaling pathway were evaluated by using immunohistochemistry, chemiluminescence, immunofluorescence, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Similar methods were also used to evaluate the levels of VEGF, VEGFR, Ang-2 and Tie, which can promote pathological angiogenesis and activate the MK/Itgα4/NF-κB signaling pathway. In vitro cell experiments were performed using potential pharmacodynamic molecules targeting integrins in DHZCP were selected by molecular docking, and the effects of these molecules on the function of LSECs were studied by Itgα4+ and Itgα6+ cell models. At the stage of LC, the animal experiments demonstrated that DHZCP mainly inhibited the MK/Itgα6 signaling pathway to increase the number and size of hepatic sinus fenestration, reversed the ET-1/NO and TXA2/NO ratios, regulated hepatic sinus relaxation and contraction balance, reduced the portal vein pressure, and inhibited cirrhotic carcinogenesis. At the HCC stage, DHZCP could also significantly inhibit the MK/Itgα4 signaling pathway, reduce pathological angiogenesis, and alleviate disease progression. The results of the cell experiments showed that Rhein, Naringenin, Liquiritin and Emodin-8-O-β-D-glucoside (PMEG) were involved in vascular regulation by affecting the MK/integrin signaling pathway. Liquiritin and PMEG mainly blocked the MK/α6 signal, which is important in regulating the vasomotor function of the liver sinus. Naringenin and Rhein mainly acted by blocked the signaling of MK/α4 action signal, which are potent molecules that inhibit pathological angiogenesis. DHZCP could improve the hepatic sinusoidal capillarization of LC and HCC by inhibiting the MK/Itgα signaling pathway and inhibited disease progression. Rhein, Naringenin, Liquiritin and PMEG were the main active molecules that affected the MK/Itgα signaling pathway. Summary of the experimental methods and process of full paper. [Display omitted] • To study the mechanism of Dahuang Zhechong Pills in inhibiting hepatic vascular disease and hepatocellular carcinoma by regulating MK and its downstream signal molecules. • With integrin α 4 and α 6 as the main target, the quality markers promoting the normalization of blood vessels in Dahuang Zhechong Pills were screened by the combination of serum drug chemistry, spectral correlation, molecular docking and other techniques. • MK has attracted much attention because it exhibits early markers of HCC and vascular regulation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Bai-Hu-Tang (BHT), a classical anti-febrile Chinese formula comprising of liquorice, anemarrhena rhizome, gypsum and rice, has been traditionally used to anti-febrile treatment and promote the production of body fluid to relieve thirst. In this paper, we aim to explore anti-febrile mechanism of BHT at protein level through analyzing alteration of differentially expressed proteins (DEPs) both lipopolysaccharide (LPS) fever syndrome and that was treated with BHT in rabbits. Materials and methods Febrile model was induced by LPS injection ( i.v. ) in rabbits, and BHT (750 mg dry extract/kg body weight) was gavaged to another group of LPS fever rabbits. After sacrifice of animals, total protein of liver tissue was isolated, and two-dimensional liquid chromatography (LC) - tandem mass spectrometry (MS) coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling analysis was employed to quantitatively identify differentially expressed proteins in two group animals, which were compared with control group. Then bioinformatic analysis of DEPs was conducted through hierarchical Clustering, Venn analysis, gene ontology (GO) annotation enrichment, and kyoto encyclopedia of genes and genomes (KEGG) pathways enrichment. Result The results demonstrated there were 63 and 109 DEPs in LPS fever group and BHT-treated group, respectively. Enrichment analysis of GO annotations indicated that BHT mainly regulated expression of some extracellular structural proteins for response to stimulus and stress. KEGG analysis showed that ribosome and phagosome were the most significant pathways. Thereinto, several proteins in phagosome pathway were significantly up-regulated by BHT, including F-actin, coronin, Rac, and major histocompatibility complex class I (MHC I), which work in phagocytosis and cross-presentation Conclusion BHT may contribute to pyrogen clearance by boosting antigenic phagocytosis, degradation, and cross presentation in the liver. [ABSTRACT FROM AUTHOR]

Different Physalis plants have been widely employed in traditional medicine for management of diabetes mellitus. Previous studies with respect to the in vivo antidiabetic activity of Physalis plants illustrated that they improved glucose and lipid metabolism in streptozotocin (STZ) -induced diabetic rats yet the mechanism of action of bioactive constituents of the different organs of Physalis plants on diabetes remains obscure. Our objective is to study the effects of the different organs of ground cherry (P. pruinosa) on diabetes in rat models and elucidate their mechanism of actions through serum pharmacochemistry combined to network pharmacology analyses and in-vivo testing. Characterization of the constituents in the drug-dosed serum samples relative to the blank serum after treatment with different extracts was performed by UPLC -MS/MS technique. The absorbed metabolites where then subjected to network pharmacology analysis to construct an interaction network linking "compound-target-pathway". In vivo verification was implemented to determine a hypothesized mechanism of action on a STZ and high fat diet induced type II diabetes mellitus (T2DM) model based on functional and enrichment analyses of the Kyoto Encyclopedia of Genes and Genome and Gene Ontology. Identification of a total of 73 compounds (22 prototypes and 51 metabolites) derived from P. pruinosa extracts was achieved through comparison of the serum samples collected from diabetic control group and extracts treated groups. The identified compounds were found to belong to different classes according to their structural type including withanolides, physalins and flavonoids. The absorbed compounds in the analyzed serum samples were considered as the potential bioactive components. The component-target network was found to have 23 nodes with 17 target genes including MAPK8, CYP1A1 and CYP1B1. Quercetin and withaferin A were found to possess the highest combined score in the C-T network. Integrated serum pharmacochemistry and network pharmacology analyses revealed the enrichment of leaves extract with the active constituents, which can be utilized in T2DM treatment. In the top KEGG pathways, lipid and atherosclerosis metabolic pathways in addition to T2DM pathways were found to be highly prioritized. The diabetic rats, which received leaves extract exhibited a substantial increment in GLUT2, INSR, IRS-1 , PI 3 K-p85 and AKT-ser473 proteins by 105%, 142%, 109%, 81% and 73%, respectively relative to the untreated diabetic group. The immunoblotting performed for MAPK and ERK1/2 part of the inflammatory pathway studied in STZ induced diabetic rats revealed that leaves, calyces and stems extracts resulted in a substantial diminish in p38-MAPK, ERK 1/2 , NF-κB, and TNF-α. Histopathological examination revealed that the hepatic histoarchitecture was substantially improved in the leaves, stems, and clayces-treated rats in comparison with untreated diabetic rats. Further, pancreatic injuries, which induced by STZ were dramatically altered by the treatment with P. pruinosa leaves, calyces and stems extracts. β-cells in diabetic rats received leaves extract disclosed moderate insulin immunostaining with a notable increase in the mean insulin area%. The study in hand offers a comprehensive study to clarify the bioactive metabolites of the different organs of P. pruinosa. The basic pharmacological effects and underlying mechanism of actions in the management of STZ and high fat diet induced T2DM were specifically covered in this paper. [Display omitted] • Mechanism of action of bioactive constituents of Physalis on diabetes type 2 suggested. • Absorbed metabolites subjected to network pharmacology to construct interaction network. • 17 target genes including MAPK8, CYP1A1 and CYP1B1 were top hits. • Diabetic rats receiving leaves extract showed increase in GLUT2, PI 3 K-p85 and AKT-ser473 proteins. • Stems extracts resulted in a significant diminish in p38-MAPK, ERK 1/2 , NF-κB, and TNF-α. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Cecropia pachystachya is a medicinal plant native to South and Central Americas used to treat asthma and diabetes. Aim of the study In this study, we evaluated the genotoxic, mutagenic and antigenotoxic effects of crude aqueous extract of C. pachystachya (CAE- Cp ) leaves. Material and methods CAE- Cp was analyzed by the Folin–Ciocalteu method to determine total phenolic and tannin contents. High performance liquid chromatography (HPLC) was used to identify major compounds. Distinct tissues from female and male adult mice were treated with 500−2000 mg/kg of CAE- Cp by gavage for the comet assay and micronucleus test analyses. In addition, peripheral blood slides of the group treated with 2000 mg/kg CAE- Cp were analyzed 3, 6, and 24 h after treatment and were exposed to hydrogen peroxide ( ex vivo ) to evaluate the genotoxic effect using the comet assay. The Salmonella /microsome assay was carried out against to TA100, TA98, TA97a, TA102, and TA1535 strains in presence and absence of the S9 mix. Results HPLC showed the presence of chlorogenic acid, isoorientin, orientin, and isovitexin as major compounds. Total phenolic and tannin contents were, respectively, 305.6±0.80 and 144.6±19.04 mg of gallic acid equivalent/g of extract. Brain DNA damage was observed in all groups treated with CAE- Cp . The H 2 O 2 challenge indicated genotoxic effect only 6 h after the administration of the extract. No increase was detected in micronucleus frequency for any group treated with the extract. Mutagenic effects were detected by Salmonella /microsome assay only in TA102 strain without S9 mix at higher doses. Conclusion The results obtained indicate that CAE- Cp was genotoxic to brain tissue. This result is supported by other papers, showing that compounds present in this extract can cross the blood-brain barrier and act on central nervous system. [ABSTRACT FROM AUTHOR]

The process of liver fibrogenesis includes a number of common and etiology-dependent or independent mechanisms and events. Up to now, there are still insufficient approved biological or chemical therapies directly targeting and reversing advanced fibrosis. The key is that once liver fibrosis is triggered, it presents a complex network control model with the activation of HSCs as the core, resulting in poor efficacy of treatment. Traditional Chinese medicine (TCM) has unique advantages in treating hepatic fibrosis because of its syndrome differentiation and treatment and comprehensive pharmacological effects of multi-channel, multi-level and multi-target. However, TCM's advantages were rarely discussed as previous reviews focused on the active ingredients of TCM and single Chinese Medicine. Therefore, this paper focuses on TCM herbal formulae's pharmacological role, target and related mechanisms in the treatment of liver fibrosis. This paper will focus on the pharmacological role, target and related mechanisms of TCM herbal formulae in the treatment of liver fibrosis. We collect English literatures or Chinese literatures with English Abstract on the treatment of liver fibrosis with TCM herbal formulae from databases including PubMed, Wiley InterScience, Science Direct OnSite/Elsevier, Ovid, Excerpta Medica Database, SpringLink, CNKI and China Biomedical Literature Database. Based on previous literatures, we summarize the TCM herbal formulae with definite anti-hepatic fibrosis effects. To some extent, classical or modern TCM herbal formulae including Yinchenhao Decoction (YCHD), Xiayuxue Decoction (XYXD), Xiaochaihutang (XCHT), Yiguanjian Decoction (YGJ), Huangqi Decoction (HQD), Dahuang Zhechong Pills (DHZC), Fuzheng Huayu Formula (FZHY), Fufang Biejia Ruangan Tablets (FFBJRG), Anluo Huaxian Pills (ALHX) and Compound 861 (Cpd861) have anti-hepatic fibrosis effect both on patients with liver fibrosis and animal models with liver fibrosis. According to the principle of syndrome differentiation and treatment, Liver fibrosis patients with different syndromes are treated with different herbal formula, which increases the difficulty of clinical efficacy research. YCHD and XYXD research lack randomized and controlled clinical trials. XCHT, YGJ and HQD research has small sample sizes despite randomized and controlled clinical trials. In contrast, most modern herbal formulae have randomized and controlled clinical trials. For instance, FZHY and ALHX recently published the research results of the combination of entecavir in the treatment of patients with chronic hepatitis B liver fibrosis or cirrhosis. Compared to anti-viral treatment with entecavir alone, this method has improved the reversion rate of liver fibrosis but still needs syndrome classification therapy of TCM. TCM Herbal formulae have a good prospect in treating liver fibrosis, but its composition of multiple drugs and a wide range of targets intensify the difficulty of studying their anti-hepatic fibrosis mechanisms. Future research needs to further study the anti-hepatic fibrosis mechanisms and select corresponding TCM herbal formula to treat patients with different syndromes of liver fibrosis or the same patient with different syndromes at different stages to achieve better curative results. The process of liver fibrogenesis includes a number of common and etiology-dependent or independent mechanisms and events. Up to now, approved biological or chemical therapies directly targeting and reversing advanced fibrosis are still lacking. Traditional Chinese Medicine (TCM) has unique advantages in anti-liver fibrosis due to its characteristics of TCM syndrome differentiation, treatment and holistic view. Studies have made tremendous progress on using herbs, ingredients and herbal formulae to treat liver fibrosis patients or animals, and this paper will focus on the development of herbal formulae to treat liver fibrosis. Image 1 [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Carthamus tinctorius is used as one of the Traditional Chinese Medicine (TCM) materials in prescriptions and composite to promote blood circulation to remove blood stasis, regulate menstruation and alleviate pain for over 2500 years. Modern pharmacological experiments have demonstrated that safflower has wide-reaching biological activities, including dilating coronary artery, modulating immune system, improving myocardial ischemia, anticoagulation and thromboprophylaxis, antioxidation, antihypoxic, antiaging, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. Materials and methods Platelet aggregation of safflower extract and main constituents in safflower were determined by PAF-induced or ADP-induced platelet aggregation in vitro. Anticoagulation activity was measured by clotting assay of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) according to the methods provided by the biological reagents provider (Sun Biochemical). Antioxidant effects of safflower were assessed using DPPH radical-scavenging activity test, ABTS radical-scavenging activity test and ferric reducing antioxidant power test. In addition, rats ovary granulosa cell proliferation activity was used for the bio-activity index on regulate menstruation of safflower. Results Safflower extract at the concentration of 0.7 g/mL ( P <0.001) and 0.5 g/mL ( P <0.01) had significantly antagonistic effect on PAF-induced platelet aggregation, compared with negative control. And the anti-platelet aggregation of 0.7 g/mL safflower extract was significantly stronger than that of positive control ( P <0.001). 0.7 g/mL of hydroxysafflor yellow A ( P <0.01 ) , anhydrosafflor yellow B ( P <0.05), 6-hydroxykaempferol-3-O-rutinoside ( P <0.05), keampferol-3-O-β-rutinoside ( P <0.01) had significant effect on platelet aggregation compared with negative control. Safflower extract at the concentration of 0.5 g/mL ( P <0.001) and 0.125 g/mL ( P <0.01) could significantly inhibit ADP-induced platelet aggregation, compared with negative control. And antagonistic effect of safflower extract was significantly stronger than the effect of positive control ( P <0.001). Adenosine ( P <0.001), anhydrosafflor yellow B ( P <0.01) and 6-hydroxykaempferol-3-O-rutinoside ( P <0.01) at the concentration of 0.5 g/mL had significant effect on ADP - induced platelet aggregation compared with negative control. 0.125 g/mL of adenosine ( P <0.05) had significant effect on ADP-induced platelet aggregation compared with negative control. The effect of 0.5 g/mL adenosine ( P <0.01) and 6-hydroxykaempferol-3-O-rutinoside ( P <0.05) was significantly stronger than that of positive control. Safflower extract at the concentration of 0.7 mg/mL ( P <0.001) and 0.5 mg/mL ( P <0.001) had significantly anticoagulation activity in PT, TT and APTT, compared with negative control. However, the respective compound didn’t have significant effect on PT and TT at experiment concentration. At the concentration of 0.7 mg/mL, hydroxysafflor yellow A ( P <0.01), 6-hydroxykaempferol-3,6,7-tri-O-β- d -glucoside ( P <0.05), 6-hydroxyapigenin-6-O-glucoside-7-O-glucuronide ( P <0.01), anhydrosafflor yellow B ( P <0.001), 6-hydroxykaempferol-3-O-rutinoside ( P <0.05) and keampferol-3-O-β-rutinoside ( P <0.05) significantly prolonged APTT, compared with negative control. At the concentration of 0.5 mg/mL, hydroxysafflor yellow A ( P <0.05) , 6-hydroxyapigenin-6-O-glucoside-7-O-glucuronide ( P <0.05 ) , anhydrosafflor yellow B ( P <0.001), 6-hydroxykaempferol-3-O-rutinoside ( P <0.05) and keampferol-3-O-β-rutinoside ( P <0.05) could significantly prolong APTT, compared with negative control. From the results of DPPH, ABTS radical scavenging activity test and Fe 3+ reduction power test, 5 mg/mL, 2.5 mg/mL and 1.25 mg/mL safflower extract had antioxidant effects. Every compound with each concentration (5 mg/mL, 2.5 mg/mL and 1.25 mg/mL) had significant effect on Fe 3+ reduction power ( P <0.001 vs. negative control). Safflower extract, cytidine, 6-hydroxy-kaempferol-3,6-di-O-β- d - glucoside-7-O-β- d -glucuronide, 6-hydroxykaemp-ferol-3,6,7-tri-O-β- D -glucoside and keampferol-3-O-β-rutinoside significantly promoted ovarian granulosa cell proliferation. Conclusion Based on previous researches, the activities of safflower extract and pure compounds isolated from safflower were studied in this paper. This study found some compounds with the effects of anti-platelet aggregation, anticoagulation, antioxidation and ovarian granulosa cell proliferation, and further revealed the possible pharmacological mechanism of safflower. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging disease. This disease is common in West Africa where more than 99% of the burden is felt and where most affected people live in remote areas with traditional medicine as primary or only option. Reports indicate that the ethnopharmacological control approach of the disease in such settings has shown promise. However, no or very few compilations of traditional knowledge in using medicinal plants to treat BU have been attempted so far. This review aimed to record medicinal plants used traditionally against BU in three countries in West Africa: Ivory Coast, Ghana and Benin and for which ethnopharmacological knowledge supported by pharmacological investigations has been reported. The information recorded in this review will support further pharmacological research to develop appropriate drugs for a better BU control. Material and methods A systematic review of the literature on ethnobotanical use and anti-BU activity of plants reported for BU treatment was performed. The approach consisted to search several resources, including Technical Reports, Books, Theses, Conference proceedings, web-based scientific databases such as publications on PubMed, Science direct, Springer, ACS, Scielo, PROTA , Google and Google scholar reporting ethnobotanical surveys and screening of natural products against Mycobacterium ulcerans . This study was limited to papers and documents published either in English or French reporting ethnopharmacological knowledge in BU treatment or pharmacological potency in vitro . This review covered the available literature up to December 2014. Results The majority of reports originated from the three most affected West African countries (Cote d’Ivoire, Ghana and Benin). Though, 98 plant species belonging to 48 families have been identified as having anti-BU use, many have received no or little attention. Most of the pharmacological studies were performed only on 54 species. To a lesser extent, ethnopharmacological knowledge was validated in vitro for only 13 species. Of those, seven species including Ricinus comminus, Cyperus cyperoides (cited as Mariscus alternifolius ) , Nicotiana tabacum, Mangifera indica, Solanum rugosum, Carica papaya, and Moringa oleifera demonstrated efficacy in hospitalised BU patients. Four isolated and characterized compounds were reported to have moderate bioactivity in vitro against M. ulcerans . Conclusions This review compiles for the first time ethnopharmacologically useful plants against BU. The phamacological potential of 13 of them has been demonstrated in vitro and support BU evidence-based traditional medicines. In addition, 7 species showed activity in BU patients and have emerged as a promising source of the traditional medicine for treatment of BU. Yet, further safety and efficacy study should be initiated prior any approval as alternative therapy. Overall, a huge gap in knowledge appeared, suggesting further well-planned and detailed investigations of the in vitro, in vivo, and safety properties of the claimed anti-BU plants. Therefore, plants with medicinal potential should be scrutinized for biologically active compounds, using bioassay-guided fractionation approach to provide new insights to find novel therapeutics for BU control. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The use of medicinal plants in Gabon contributes widely to the primary health care of the people of this area of Central Africa. This paper investigates the pharmacological properties of Dichrostachys cinerea, the plant barks are traditionally used by Gabonese and Ivorian populations to treat bronchial asthma, rheumatism, and other various diseases. Although D. cinerea barks have been reported to be used by population to facilitate childbirth, to the best of our knowledge no scientific evidence has been published. Aim of study In the present study, we investigated the pharmacological properties of D. cinerea methanolic extract, on isolated uterine smooth muscle and compared its effects to those of oxytocin, which is used by obstetricians to facilitate childbirth. We also explored the possible mechanism pathways of the in vitro uterine contraction induced by D. cinerea . Materials and methods The effects of different concentrations (3.2 µg/ml, 16 µg/ml, 80 µg/ml, 400 µg/ml, and 2 mg/ml) of the methanolic extract of D. cinerea on isolated strips of the uteri of pregnant rats were studied. These effects were compared to those of oxytocin (8.4×10 –5 µg/ml, 8.4×10 –4 µg/ml, 8.4×10 –3 µg/ml, 8.4×10 –2 µg/ml). The EC (50) and E (max) was determined graphically and statistically analysed using one-way ANOVA and Dunnett post hoc test. Results Cumulative concentrations of D. cinerea have caused rise in the contractile force of the uterine fragments that were isolated from the pregnant rats, as seen with oxytocin concentrations. We observed contractions amplitude of 30.41 mN (12%) at 80 µg/ml and amplitude of 39.68 mN (14.17%) at 400 µg/ml for D. cinerea. In parallel, oxytocin concentration of 8.4×10 –3 µg/ml induced contractions of 45.82 mN with the highest concentration (8.4×10 –2 µg/ml) that induced contractions of 55.82 mN. Conclusions Our results revealed that D. cinerea increased the contractile force and the frequency of muscle contractions. These findings support the use of D. cinerea to facilitate childbirth, as it has been used in traditional medicine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Triticum vulgare has been extensively used in traditional medicine thanks to its properties of accelerating tissue repair. The aqueous extract of Triticum vulgare (TVE) is currently an active component used by Farmaceutici Damor in the manufacture of certain pharmaceutical products already marketed in Italy and abroad under the brand name Fitostimoline ® , in the formulation of cream and medicated gauze and is commonly used for the treatment of decubitus ulcers, sores, burns, scarring delays, dystrophic diseases, and, more broadly, in the presence of problems relating to re-epithelialization or tissue regeneration. The active components of Fitostimoline ® -based products determine a marked acceleration of tissutal repairing processes, stimulate chemotaxis and the fibroblastic maturation, and significantly increase the fibroblastic index, which are crucial points in the repairing processes. The aim of the present paper was to identify and characterize the active fractions of TVE responsible for the pharmacological effect in tissutal repairing processes. Materials and methods Several fractions obtained from TVE by ultrafiltration procedures and HPAE chromatography were tested to measure their growth-enhancing activity on NIH-3T3 fibroblasts. The healing action of the same fractions, prepared as cream formulation, was assessed in rat subjected to two different models of skin lesion, skin scarification and excision. Results Our results showed a pro-proliferative effect of the fractions ST-98 and K>1000 in NIH-3T3 fibroblasts. Moreover these fractions formulated as cream preparations were effective also in in vivo models of skin lesion. Conclusions The results of the present study showed that these active fractions of TVE are responsible for its pro-proliferative effect. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Sandpaper [ Ficus exasperata Vahl (Moraceae)] leaf has been reportedly used in folklore for the management/treatment of cardiovascular diseases with little/or no scientific basis for their action. This study sought to investigate the effect of dietary supplementation of sandpaper leaf on angiotensin-I converting enzyme (ACE) activity in hypercholesterolemia as well as the effect of their phenolic extract on this enzyme in vitro . Materials and methods The phenolic extract was prepared, then, the inhibitory effect of the leaf extract on ACE was determined in vitro . Thereafter, the effect of dietary supplementation of sandpaper leaf on angiotensin-I converting enzyme (ACE) activity in high cholesterol diet fed rats for 14 days was evaluated as well as some biochemical parameters. Results The result revealed that under in vitro condition, the phenolic extract inhibited ACE (IC 50 =14.7 µg/mL) in a dose-dependent manner (0–10 µg/mL). Feeding high cholesterol diets to rats caused a significant ( P <0.05) increase in the ACE activity. However, there was a significant ( P <0.05) decrease in the ACE activity as a result of supplementation with the sand paper leaves. Furthermore, there was a significant ( P <0.05) increase in the plasma lipid profile with a concomitant increase in malondialdehyde (MDA) content in rat liver and heart tissues. However, supplementing the diet with sandpaper leaf (either 10% or 20%) caused a significant ( P <0.05) decrease in the plasma total cholesterol (TC), triglyceride (TG), very low density lipoprotein-cholesterol (VLDL-C), and low-density lipoprotein-cholesterol levels (LDL-C), and in MDA content in the tissues. Conversely, supplementation caused a significant ( P <0.05) increase in plasma high-density lipoprotein-cholesterol level when compared with the control diet. Reversed phase HPLC analysis of the extract revealed Quercitrin (43.7 mg/g), chlorogenic acid (42.8 mg/g) and caffeic acid (33.9 mg/g) as the major phenolics in the leaf. Conclusion The inhibition of ACE activity and prevention of hypercholesterolemia by sandpaper leaf could be part of the possible mechanism underlying its anti-hypertensive property which could lay credence to its use in folk medicine. However, these activities may be directly/indirectly attributed to the polyphenolics present. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Red sage ( Salvia miltiorrhiza Bunge), also known as Danshen in Chinese, has been used historically and is currently exploited in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM). With the advance of modern analytical technology, a multitude of bone-targeting, pharmaceutically active, compounds has been isolated and characterized from various sources of TCM including those produced in Salvia miltiorrhiza root. The aim of the review is to provide a comprehensive overview about the historical TCM interpretation of the action of Salvia miltiorrhiza in osteoporosis, its use clinical trials, its main phytochemical constituents, and its action on bone-resorptive and bone formation-stimulating mechanisms in in vitro and in vivo studies. Materials and methods Literature sources used were Pubmed, CNKI.net, Cqvip.com, PubChem, and the Web of Science. For the inquiry, keywords such as Salvia, danshen, osteoporosis, bone, osteoclast and osteoblast were used in various combinations. About 130 research papers and reviews were consulted. Results In TCM, the anti-osteopororotic effect of Salvia miltiorrhiza is ascribed to its action on liver and blood stasis as main therapeutic targets defining osteoporosis. 36 clinical trials were identified which used Salvia miltiorrhiza in combination with other herbs and components to treat post-menopausal, senile, and secondary osteoporosis. On average the trials were characterized by high efficacy (>80%) and low toxicity problems. However, various limitations such as small patient samples, short treatment duration, frequent lack of detailed numerical data, and no clear endpoints must be taken into consideration. To date, more than 100 individual compounds have been isolated from this plant and tested in various animal models and biochemical assays. Compounds display anti-resorptive and bone formation-stimulating features targeting different pathways in the bone remodeling cycle. Pathways affected include the activation of osteoblasts, the modulation of osteoclastogenesis, and the inhibition of collagen degradation by cathepsin K. Conclusions The inclusion of Salvia miltiorrhiza in more than 30% of all herbal clinical trials successfully targeting osteoporosis has stimulated significant interest in the identification and characterization of individual constituents of this herb. The review highlights the anti-osteoporotic potential of Salvia miltiorrhiza in clinical applications and the potential of the herb to provide potent compounds targeting specific pathways in bone resorption and bone formation. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: In the recent years, the international community has attached increasing importance to possible toxicity associated with Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major concerns, a fundamental pathological process induced by toxicant. This paper is in an attempt to identify the hepatotoxic components in Xanthium strumarium L. fruits (XSF) and interpret the toxicological mechanism induced by XSF. Materials and methods: XSF extract was prepared and seven characteristic components were isolated and identified in XSF water extracts. We evaluated their hepatotoxicity effect on cell proliferation and lactate dehydrogenase (LDH) activity in L-02 and BRL liver cell line. An integrated metabonomics study using high-resolution 1H nuclear magnetic resonance (1H NMR) spectroscopy combined with multivariate statistical analysis was undertake to elucidate the hepatotoxicity mechanism induced in rats by XSF. The urine and serum metabolites were measured after treatment of rats with XSF (7.5, 15.0 and 30.0g/kg/day) for 5 days. Results: The results showed that atractyloside, carboxyatractyloside, 4'-desulphate-atractyloside and XSF induced significant cytotoxic effects in both L-02 and BRL liver cell lines, indicating that atractyloside, carboxyatractyloside, and 4'-desulphate-atractyloside were the toxic components of XSF. When rats were treated with XSF at 30.0g/kg the hepatotoxicity was reflected in the changes observed in serum biochemical profiles and by the histopathological examination of the liver. The levels of VLDL/LDL, 3-HB, lactate, acetate, acetone and glutamate in serum were increased in this group, while d-glucose, choline and valine were decreased. The elevation in the levels of succinate, citrate, 2-oxo-glutamate, glycine, 3-HB, acetate, lactate, hippurate, dimethylglycine, methylamine, dimethylamine, phenylalanine and tryptophan was observed in urine, in contrast a reduction in the intensities of taurine, d-glucose, N-acetyl-glucoprotein and trimethylamine-N-oxide (TMAO) was observed. Conclusions: The results demonstrate that the major hepatotoxicity constituents are atractyloside, carboxyatractyloside and 4'-desulphate-atractyloside, and the hepatotoxicity of XSF involves mitochondrial inability, fatty acid metabolism, and some amino acids metabolism. This integrated 1H NMR -based metabolic profiling approach has been able to capture and probe the metabolic alterations associated with the onset and progression of hepatotoxicity induced by XSF, and permits a comprehensive understanding of systemic toxicity for phytochemicals and other types of xenobiotic agents. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: In 1962 ethnopharmacologists, Hofmann and Wasson, undertook an expedition to Oaxaca, Mexico. These two researchers were the first scientists to collect a flowering specimen of Salvia divinorum allowing the identification of this species. While the species' traditional use is confined to a very small region of Mexico, since Hofmann and Wasson's expedition 50 years ago, Salvia divinorum has become globally recognized for its main active constituent, the diterpene salvinorin A, which has a unique effect on human physiology. Salvinorin A is a kappa-opioid agonist and the first reported psychoactive diterpene. Methods: This review concentrates on the investigation of Salvia divinorum over the last 50 years including ethnobotany, ethnopharmacology, taxonomy, systematics, genetics, chemistry and pharmacodynamic and pharmacokinetic research. For the purpose of this review, online search engines were used to find relevant research. Searches were conducted between October 2011 and September 2013 using the search term “Salvia divinorum”. Papers were excluded if they described synthetic chemical synthesis of salvinorin A or analogues. Results: Ethnobotanically there is a comprehensive body of research describing the traditional Mazatec use of the plant, however, the modern ethnobotanical use of this plant is not well documented. There are a limited number of botanical investigations into this plant and there are still several aspects of the botany of Salvia divinorum which need further investigation. One study has investigated the phylogenetic relationship of Salvia divinorum to other species in the genus. To date the main focus of chemistry research on Salvia divinorum has been salvinorin A, the main active compound in Salvia divinorum, and other related diterpenoids. Finally, the effects of salvinorin A, a KOR agonist, have primarily been investigated using animal models. Conclusions: As Salvia divinorum use increases worldwide, the emerging cultural use patterns will warrant more research. More botanical information is also needed to better understand this species, including germination, pollination vector and a better understanding of the endemic environment of Salvia divinorum. As well there is a gap in the genetic knowledge of this species and very little is known about its intra-species genetics. The terpenes in Salvia divinorum are very well documented, however, other classes of constituents in this species warrant further investigation and identification. To date, the majority of the pharmacology research on Salvia divinorum has focused on the effects of salvinorin A using animal models. Published human studies have not reported any harmful effects when salvinorin A is administered within the dose range of 0.375–21µg/kg but what are the implications when applied to a larger population? More data on the toxicology and safety of Salvia divinorum are needed before larger scale clinical trials of the potential therapeutic effects of Salvia divinorum and salvinorin A are undertaken. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The dried fruit of Psoralea corylifolia L. has been used to prevent and treat vitiligo, osteoporosis, arthralgia and asthma in Traditional Chinese Medicine for some 1600 years. Psoralen (P), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) are the major coumarins and coumarin-related benzofuran glycosides in Psoraleae Fructus, which have been reported to show estrogen-like activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. The first aim of this study is to develop a rapid, sensitive and selective ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) approach for simultaneous determination of PO, IPO, P and IP in rat plasma and samples collected from in vitro incubation experiments. The second aim is to investigate the pharmacokinetic properties of PO, IPO, P and IP after oral administration of Psoralea corylifolia extract (PCE) to rats. The third aim is to confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions. Materials and methods: A UPLC–MS/MS method with a C18 column and a mobile phase of methanol-0.1% aqueous formic acid was validated according to the criteria in FDA guidelines about bioanalytical method, which was developed to investigate the pharmacokinetic behavior of PO, IPO, P and IP from PCE and the metabolic pathways of PO to P or IPO to IP. Results: The criteria for establishment of a new UPLC–MS/MS method including selectivity, linearity, accuracy, precision, extraction recovery, matrix effect and stability were validated. This method was successfully applied to the quantitative determination of PO, IPO, P and IP in biological samples collected from both in vitro incubations and in vivo rat experiments. After oral administration of PCE to rat, pharmacokinetic parameters of these four compounds indicated that in vivo biotransformation may occur between PO and P or IPO and IP. Purified benzofuran glycosides fraction (PBGF), containing only PO and IPO, was orally administered to rats to further confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions. An in vitro incubation study elucidated that PO and IPO were metabolized to P and IP by intestinal microflora through de-glucosylation. Conclusions: This paper developed a rapid, sensitive and selective UPLC–MS/MS method for simultaneous determination of PO, IPO, P and IP from PCE in biological samples, and investigated on their comprehensive in vivo and in vitro pharmacokinetic studies. These obtained results showed that the metabolism by intestinal bacteria plays an important role in pharmacological effects of orally administered PCE. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Salvia miltiorrhiza (SM, also known as DanShen) is one of the well-known widely used Chinese herbal medicines in clinical, containing phenolic compounds and potent antioxidant properties. Salvianolic acid A (SAA) is the most potent component of SM. A modern experimental strategy for treating myocardial ischemia is to induce neovascularization of the heart by the use of "angiogens", mediators that induce the formation of blood vessels, or angiogenesis. Studies demonstrated that coronary collateral vessels protect ischemic myocardium after coronary obstruction; therefore, we sought to examine whether SAA could stimulate myocardial angiogenesis. Materials and methods: Male Sprague–Dawley rats myocardial infarct (MI) induced by ligation of left anterior descending coronary artery (LAD) were randomly divided into five groups: sham-operated group; LAD occlusion + administration of physiological saline (vehicle treated group); LAD occlusion + administration of different concentrations of SAA (10, 5.0 and 2.5mg/kg/d). Infarct size and capillary density in the infarct region were measured with a previous experimental method. Immunohistological analysis was performed to measure vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) expressions. The secretion of matrix metalloproteinase type X (MMP-9) was evaluated in serum of post-ischemic rats. We also performed the experiments of SAA on rat endothelial progenitor cells (EPCs) numbers and the capacity of migration and vasculargenesis. Results: SAA potentiated the ischemia-induced neovascularization after 1week post-operation when compared to vehicle treated group. This effect could be attributed to an increased formation of VEGF, VEGFR-2, and MMP-9 as well as the promotion of numbers and functions of EPCs. Conclusion: These findings show that SAA has potent proangiogenic properties by promoting the expression of proangiogenic factors, and the functions of EPCs, indicating that SAA might contribute to the protective effect against coronary disease. Chemical compound studied in this paper is salvianolic acid A (PubChem CID: 5281793) [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Acanthopanax senticosus, classified into the family of Araliaceae, has been known for thousands of years as a remedy and is used to treat various diseases in traditional Chinese medicine system including hypertension, ischemic heart disease and hepatitis. Aim of the study: This study aimed to examine the protective effects of aqueous extract from Acanthopanax senticosus (ASE) on corticosterone-induced neurotoxicity and its possible mechanisms, using PC12 cells as a suitable in vitro model of depression. Materials and methods: In this paper, PC12 cells were treated with 200μM of corticosterone in the absence or presence of ASE in varying concentrations for 24h. Then, cell viability was measured by MTT assay. The release amount of lactate dehydrogenase (LDH) was quantified using LDH assay kit. Apoptosis of PC12 cells was measured by Annexin V-FITC and PI labeling. The intracellular Ca2+ content was tested by fluorescent labeling. The mRNA level of brain-derived neurotrophic factor (BDNF) was examined by real-time RT-PCR, and the expression of cAMP response element binding protein (CREB) was determined by western blotting. Results: The results showed that treatment with 200μM of corticosterone could induce cytotoxicity in PC12 cells. However, different concentrations of ASE (50, 100, 200, and 400μg/mL) significantly increased the cell viability, decreased the LDH release, suppressed the apoptosis of PC12 cells, attenuated the intracellular Ca2+ overloading, up-regulated the BDNF mRNA level and CREB protein expression compared with the corresponding corticosterone-treated group. Conclusion: The present results suggest that ASE exerts a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be one of the acting mechanisms that accounts for the in vivo antidepressant activity of ASE. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Ethnobotanical reports on more than 100 southern African medicinal plants with dermatological relevance have been highlighted, yet there is still limited scientific data to support claims for their antimicrobial effectiveness against skin pathogens. Guided by ethnobotanical data, this paper explores the antimicrobial efficacies of southern African medicinal plants used to treat skin ailments. Aim of the study: To investigate the antimicrobial properties of southern African medicinal plants against dermatologically relevant pathogens. The study also aimed at providing a scientific rationale for the traditional use of plant combinations to treat skin diseases and the isolation of the bio-active compound from the most active species, Aristea ecklonii (Iridaceae). Materials and methods: Organic and aqueous extracts (132) were prepared from 47 plant species and screened for antimicrobial properties against dermatologically relevant pathogens using the micro-titre plate dilution method. Four different plant combinations were investigated for interactive properties and the sum of the fractional inhibitory concentration (ƩFIC) calculated. Isobolograms were used to further investigate the antimicrobial interactive properties of Pentanisia prunelloides combined with Elephantorrhiza elephantina at varied ratios. A bioactivity-guided fractionation process was adopted to fractionate the organic leaf extract of Aristea ecklonii. Results: Plants demonstrating notable broad-spectrum activities (MIC values ≤1.00mg/ml) against the tested pathogens included extracts from Aristea ecklonii, Chenopodium ambrosioides, Diospyros mespiliformis, Elephantorrhiza elephantina, Eucalyptus camaldulensis, Gunnera perpensa, Harpephyllum caffrum, Hypericum perforatum, Melianthus comosus, Terminalia sericea and Warburgia salutaris. The organic extract of Elephantorrhiza elephantina, a plant reportedly used to treat acne vulgaris, demonstrated noteworthy antimicrobial activity (MIC value of 0.05mg/ml) against Propionibacterium acnes. Similarly, Diospyros mespiliformis reported for its traditional use to treat ringworm, also displayed noteworthy antimicrobial activity against Trichophyton mentagrophytes (MIC 0.10mg/ml) and Microsporum canis (MIC 0.50mg/ml). The aqueous root extracts of Pentanisia prunelloides combined (1:1) with Elephantorrhiza elephantina displayed synergistic interactions (ƩFIC values 0.31–0.38) against Staphylococcus aureus, gentamycin–methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans. Fractionation of Aristea ecklonii resulted in the isolation of the known bio-active compound, plumbagin, displaying noteworthy antimicrobial activity (MIC range between 2.00μg/ml and 16.00μg/ml). Conclusion: Most of the plant extracts demonstrated pathogen specific antimicrobial effects with a few exhibiting broad-spectrum activities. Positive antimicrobial effects noted for plants such as Elephantorrhiza elephantina and Diospyros mespiliformis used for acne vulgaris and ringworm infections, respectively, give some validation to their reported traditiona l uses. Synergistic interactions noted for Pentanisia prunelloides combined with Elephantorrhiza elephantina validate an enhanced antimicrobial effect when used in combination. Noteworthy antimicrobial activities (MIC range between 2.00μg/ml and 16.00μg/ml) were observed for plumbagin isolated from Aristea ecklonii. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Aanthopanax senticosus (A. senticosus) Harms is a classical adaptogenic agent used in China. It has been applied as an analeptic aid to improve weakened physical status. However, little is known about the effects of A. senticosus on inflammatory disease processes. Materials and methods: Flies fed with standard cornmeal–yeast medium were used as controls, and the treatment groups contained 10% of A. senticosus aqueous extracts (root or fruit) in standard medium. Survival rate was performed by feeding a vial containing five layers of filter paper hydrated with 5% sucrose solution contaminated with pathogenic or toxic compounds. Imaging of the guts was viewed under the microscope. Death cells were detected by 7-AAD staining. Results: The A. senticosus extract improved the survival rate, attenuated the death of intestinal epithelial cells, promoted the expression of antimicrobial peptide genes, and decreased the formation of melanotic masses. Moreover, our results indicated that the protective effect of fruit is much higher than that of root extracts. Conclusions: A. senticosus extracts have a protective effect on Drosophila gut immunity and stress response, and may contribute to the prevention of inflammatory diseases induced by pathogenic and toxic compounds. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Rhein (Rh), baicalin (BG) and berberine (Be) are important coexisted constituents of San-Huang-Xie-Xin-Tang, which was widely used in traditional Chinese medicine for the treatment of gastritis, hypertension, gastric bleeding and peptic ulcers, etc. Aim of the study: Based on the extensive phase II conjugation reactions of polyphenols (Rh and BG) in vivo, the aims of the present study were to investigate the effects of combination (Rh, BG and Be) on the system exposures of total Rh and BG involving the phase II conjugates metabolites and its possible mechanism. Materials and methods: A 3×3 Latin square single heavy design was used to investigate the pharmacokinetics influence of total Rh and BG after combination of Be by treating plasma samples with β-glucuronidase/sulfatase both in beagle dogs and Wistar rats. In vitro and in situ experiment models including in situ rat intestinal perfusion, Caco-2 cell monolayer transport and small intestinal flora incubation system were used to discuss the possible mechanism. Results: The results of pharmacokinetic interactions showed that combination significantly reduced the system exposures of total Rh and BG. Compared with Rh or BG alone, the mean area under concentration-time curves (AUC0–t ) of total Rh and BG reduced by 31% and 77% in beagle dog experiment. In Wistar rat experiment, the AUC0–t of total Rh and BG reduced by 22% and 21%. Subsequently, the results of in situ rat intestinal perfusion and small intestinal flora incubation system tests revealed that combination may decrease the absorption and metabolism of BG. However, combination could not affect the transport profile of BG across the Caco-2 cell. Moreover, combination did not affect the absorption or metabolism profile of Rh in all three in situ/in vitro experiments. Conclusions: It was deduced that the possible mechanism of the reduction of the system exposures of total Rh and BG was related to that combination decreased the metabolism of BG to B or the phase II conjugates of Rh/BG excreted from liver/bile duct to their free aglycones in vivo by inhibiting intestinal flora. The potent effects of combination on the phase II conjugates of Rh and B in pharmacokinetics, shown in this paper, indicated that more attention should be paid to the phase II conjugates metabolites of these polyphenols (undergo extensive phase II conjugation reactions in vivo) when applied herbal products composed of these coexist compounds. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological Relevance: Leaves of Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson (yacon) have been used since pre-Columbian times in the Andean region to prepare medicinal herbal tea with beneficial health properties. However, there are still disagreements about the safe use. This work was carried out to evaluate the toxicity profile of both, 10% decoction of yacon leaves and their major active lactone, enhydrin. Materials and methods: In vitro cytotoxicity assays were performed with Hep-G2, COS1, CHO-K1 and Vero cell lines using a test of metabolic competence based upon assessment of mitochondrial performance. In vivo toxicity study was performed in adult Wistar rats. In the acute oral toxicity each group of rats was orally given a single dose of 10% decoction or enhydrin. General condition, behavior and mortality were recorded for up to 14 days post treatment. In subchronic toxicity studies, both products were given orally for 90 days to rats. Body weight and food intakes were observed weekly. Hematological, clinical chemistry parameters and organ weight were determined in all animals at the end of the experimental period. Results: Cell viability decreased in a concentration dependent fashion when cells were incubated with 2–200μg of 10% decoction and 0.015–7.5μg of enhydrin. In acute study in rats, there were no deaths or signs of toxicity observed after oral administration of single doses of 10% decoction or enhydrin at any dose level up to the highest dose tested (14.0g/kg and 0.32g/kg, respectively). In subchronic studies in rats, both products administered orally for 90 days at daily doses of 0.07, 0.14 and 0.28g 10% decoction/kg and 0.4, 0.8 and 8.0mg enhydrin/kg, did not caused haematological, biochemical and histological alterations. Conclusions: The results presented in this paper lead us to the conclusion that the use of 10% decoction and enhydrin is safe in rat at doses in which it is demonstrated the hypoglycaemic effect. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Vitis thunbergii var. taiwaniana are traditionally used for the treatment of diarrhea, fracture and injury, jaundice, and hepatitis in Taiwan. Aim of the study: The hepatoprotective activity of its plant extracts seems to be been associated with its antioxidant activity. This paper aims to investigate the in vitro and in vivo antioxidant effects of the ethanol extract of Vitis thunbergii (EVT). Materials and methods: In HPLC analysis, the fingerprint chromatogram of EVT was established. Antioxidant ability of EVT was investigated by employing several established in vitro methods. In vivo antioxidant activity was tested against CCl4-induced toxicity in mice. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected in the blood to indicate hepatic injury. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) contents were evaluated for oxidative stress in hepatic injury. Moreover, histopathological observation was assayed for the degree of hepatic injury. Results: EVT exhibited strong antioxidant ability in vitro. After oral administration of EVT significantly decreased ALT and AST, and ameliorated the oxidative stress in hepatic tissue and increased the activity of CAT, SOD, GPx, and GSH. Serum tumor necrosis factor-alpha (TNF-α), interleukin−1β (IL-1β), and nitric oxide (NO) were decreased in the group treated with CCl4 plus EVT. Western blotting revealed that EVT blocked protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in CCl4-treated rats, significantly. Histopathological examination of livers showed that EVT reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl4-treated rats. Conclusion: This study suggests that EVT possesses antioxidant effects in vitro and hepatoprotective effect on acute liver injuries induced by CCl4 in vivo, and the results suggested that the effect of EVT against CCl4-induced liver damage is related to its antioxidant properties. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Fuzi, which is the processed lateral roots of Aconitum Carmichaeli. Debx and is widely distributed over the southwest provinces of China, is recognised for its anti-inflammatory and analgesic effects. Aim of the study: The pharmacokinetic properties of Fuzi are inadequately understood. Aconitine, the primary highly toxic ingredient of Fuzi, is well known as the target marker of Fuzi. The purpose of the present study is to investigate the pharmacokinetic behaviours of aconitine in vivo following single and multiple administrations of processed Fuzi extracts and to compare the pharmacokinetic characteristics of aconitine after administrations of pure aconitine or Fuzi extracts as well as compare the difference at single dose and multiple doses. The in vitro aconitine protein binding in plasma through equilibrium dialysis was also examined. Methods: A high performance liquid chromatography (HPLC) method was developed for the determination of aconitine in Fuzi crude extracts and a fast ultra performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) was developed to investigate the pharmacokinetic behaviour of aconitine as the targeted marker of Fuzi. Results: The absolute bioavailability (F %) after the administration of 0.5mg/kg aconitine and Fuzi extract (0.118mg/kg aconitine) in rat was 8.24±2.52% and 4.72±2.66%, respectively. Aconitine absorption was very fast at the t max 30.08±9.73min for pure aconitine and 58.00±21.68min for Fuzi extract administration. Aconitine was also eliminated rapidly with a short half-life (i.v., 80.98±6.40min) and a low rate of protein bounding (23.9–31.9%). No significance was observed on all the pharmacokinetics parameters following the single and multiple doses of pure aconitine (ANOVA, p >0.05). However, the absorption of aconitine after multiple administrations of Fuzi extract was much faster than that of a single dose (t max: 58.00±21.68 vs. 20.00±8.66min, p <0.05), and the area under the plasma concentration–time curve (AUC) was higher than that of a single dose. Conclusions: The pharmacokinetic behaviour of processed Fuzi was determined in this paper. The aconitine has low bioavailability. No variation in the pharmacokinetic behaviours of pure aconitine was observed after single and multiple administrations. In contrast, multiple administrations of processed Fuzi extract could result in variations in its pharmacokinetic behaviour in AUC and t max indicating that multiple dose might increase the bioavailability of aconitine, which may result in its toxicity. In addition, aconitine has a low protein bounding (23.9–31.9%), resulting in its rapid elimination. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: In Mexico, Opuntia streptacantha is used as part of a traditional medicine in the treatment of diabetes mellitus. Several studies have reported an anti-hyperglycemic effect from the plant, but none have focused on finding a mechanism of action to explain these results. This paper focuses on one of the most recurrent hypotheses for the effect of O. streptacantha: the mechanism of action is the hydrolysis of disaccharides, either by enzymatically inhibiting the alpha glucosidase inhibitors (AGIs) or mechanically acting as a barrier. Materials and methods: To test our hypothesis, three different experiments were performed. A maltose tolerance test was carried out using the total extract (TE) and the juice of the plant. Six different extracts were tested in a free-enzyme assay, four of which were aqueous extracts varying according to the procedure of removing the insoluble particles in an attempt to reduce the loss of the water-soluble compounds. The main component of the total extract, a derivative of (4-hydroxy)-phenyl acetic acid, was also tested. For both the maltose tolerance test and the free-enzyme assay, acarbose was used as a control drug. Finally, an everted small intestine assay was also performed. Results and conclusions: The maltose tolerance test confirmed that an anti-hyperglycemic effect occurs at doses of 100mg/kg TE and 4mL/kg juice. No inhibition on AGIs was observed in the free-enzyme assay, and neither a mechanic nor enzymatic effect on disaccharide hydrolysis was observed in the everted intestine assay. Conclusions: The anti-hyperglycemic effect of O. streptacantha was confirmed, and the results presented here contribute to the understanding that this effect is not due to the action on alpha-glucosidases or related to the intestinal hydrolysis of disaccharides. [Copyright &y& Elsevier]

Abstract: Aim of the study: Species of Lychnophora are used in Brazilian folk medicine as analgesic and anti-inflammatory agents. Chlorogenic acid (CGA) and their analogues are important components of polar extracts of these species, as well in several European and Asian medicinal plants. Some of these phenolic compounds display anti-inflammatory effects. In this paper we report the isolation of CGA from Lychnophora salicifolia and its effects on functions involved in neutrophils locomotion. Materials and methods: LC–MS n data confirmed the presence of CGA in the plant. Actions of CGA were investigated on neutrophils obtained from peritoneal cavity of Wistar rats (4h after 1% oyster glycogen solution injection; 10ml), and incubated with vehicle or with 50, 100 or 1000μM CGA in presence of lipopolysaccharide from Escherichia coli (LPS, 5μg/ml). Nitric oxide (NO; Griess reaction); prostaglandin E2 (PGE2), interleukin-1β (IL-1β) and tumor necrosis factor-α [TNF-α; enzyme-linked immunosorbent assay (EIA)]; protein (flow cytometry) and gene (RT-PCR) expression of L-selectin, β2integrin and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were quantified. In vitro neutrophil adhesion to primary culture of microvascular endothelial cell (PMEC) and neutrophil migration in response to formyl-methionil-leucil-phenilalanine (fMLP, 10−8M, Boyden chamber) was determined. Results: CGA treatment did not modify the secretion of inflammatory mediators, but inhibited L-selectin cleavage and reduced β2 integrin, independently from its mRNA synthesis, and reduced membrane PECAM-1 expression; inhibited neutrophil adhesion and neutrophil migration induced by fMLP. Conclusions: Based on these findings, we highlight the direct inhibitory actions of CGA on adhesive and locomotion properties of neutrophils, which may contribute to its anti-inflammatory effects and help to explain the use of Lychnophora salicifolia as an anti-inflammatory agent. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Jiang-Zhi-Ning (JZN) is composed of four Chinese herbs, i.e., Fleeceflower Root, Fructus Crataegi, Folium Nelumbinis and Semen Cassiae. It was used to strengthen blood circulation of coronary artery, arrhythmia and hyperlipidemia. Aim of the study: The main objective of this paper is to evaluate lipid-lowering and antioxidant activities of extract and effective fraction of JZN by using in vitro experiments on hyperlipidemic rats. Moreover, in vivo experiments on cells were performed to investigate lipid-lowering and antioxidant activities of effective fraction and active constituents of JZN. Materials and method: Wistar rats with high fat diet-induced hyperlipidemia were used as in vitro models to study biological effects of lipid-lowering and antioxidant activities of extract and effective fraction of JZN. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Coronary Index and Atherogenic Index were investigated to evaluate lipid-lowering effects of extract and effective fraction of JZN. Serum total nitric oxide synthase (NOS), nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were detected to measure antioxidant effects of extract and effective fraction of JZN. Furthermore, oxidized low-density lipoprotein (Ox-LDL) injured human umbilical vein endothelial cell (HUVEC) model was employed as in vivo experiment to study lipid-lowering and antioxidant effects of effective fraction and active constituents of JZN. NO, ET-1, MDA SOD and T-AOC in HUVECs or culture media were investigated to evaluate antioxidant activity of effective fraction and active constituents of JZN. Using human hepatoma cell line Bel-7402, reverse transcription polymerase chain reaction (RT-PCR) technology was performed to investigate cholesterol metabolism effects of effective fraction and active constituents of JZN. Expressions of low density lipoprotein receptor (LDL-R), 3-hydroxy-3-methyl-HMG-coenzyme A reductase (HMG-CoAR), and cholesterol 7α-hydroxylase (CYP7A1) mRNA of the liver cells were investigated to evaluate JZN on associated receptor and enzymes of cholesterol metabolism. High-performance liquid chromatography (HPLC) and spectrophotometry were used to study the impact of effective fraction and active constituents of JZN on synthesis and translation of cholesterol during the process of metabolism by measuring inside and extracellular contents of total bile acid (TBA) of Bel-7402. Results: Extract and effective fraction of JZN significantly reduced contents of TC, TG and LDL-C, CRI and AI in hyperlipidemic rats as well as significantly increased contents of HDL-C in the rats. Moreover, they significantly enhanced the activity of NOS and increased contents of NO. They also caused significant reductions in contents of ET-1 and MDA as well as significant increase in SOD activity and T-AOC in the hyperlipidemic rats. Several indicators were found to be concentration-dependent. As far as in vivo experiments to investigate biological activities of effective fraction and active constituents of JZN were concerned, it was found that they restored and enhanced the vitality of HUVECs with a concentration-dependent manner as well as content of NO in the culture media of HUVEC. They caused reductions in the contents of ET-1 in the culture media of HUVEC and contents of MDA in HUVECs. They also caused an increase in the vitality of SOD and T-AOC in HUVECs. Furthermore, they enhanced LDL-RmRNA expression, with a concentration-dependent manner. Low and medium concentrations of effective fraction and active constituents of JZN could inhibit expression of HMG-CoAR mRNA. High concentration counterpart could enhance expression of the HMG-CoAR mRNA. They enhanced expression of CYP7A1 mRNA in a concentration-dependent manner. Finally, they caused reductions in the contents of cholesterol in Bel-7402. They also increased intercellular content of total bile acid as well as lowered extracellular contents of TBA in the cells in a concentration-dependent manner. Conclusion: We demonstrated for the first time lipid-lowering and antioxidant activities of extract and effective fractions as well as active constituents of JZN. Active constituents of JZN had the same biological effects with effective fraction and extract of JZN. Therefore, this study supports its ethnopharmacological use in Traditional Chinese Medicine to manage hyperlipidemia and paves a basis for establishing quality control method of Chinese medicine. [Copyright &y& Elsevier]

Aim of the study: This paper aimed to elucidate the traditional use of Rosmarinus officinalis through the investigation of cholinergic activities and neuronal differentiation in rat pheochromocytoma PC12 cells. These effects were examined in relation to the plant''s habitat, the extraction procedure, and the major active compounds of R. officinalis. Materials and methods: Cell viability, cell differentiation, acetylcholinesterase (AChE) activity, total choline, acetylcholine (ACh) and extracellular signal-regulated kinases (ERK1/2) were determined in PC12 cells treated with extracts and HPLC-identified polyphenols of R. officinalis originated from Tunisian semi-arid and subhumid area in comparison with nerve growth factor (NGF). Results: R. officinalis extracts potentiated cell differentiation and significantly enhanced AChE activity in PC12 cells. The highest AChE activity was induced by semi-arid hydro-ethanolic extract (137% of control). Among HPLC-identified and screened polyphenols, carnosic acid (CA) and rosmarinic acid (RA) significantly induced cell differentiation, increased ACh level, and enhanced AChE activity in PC12 cells. U0126, inhibitor of ERK1/2, significantly reduced CA and RA effects on cell differentiation and AChE activity. Conclusions: R. officinalis’ CA and RA exhibited neurotrophic effects in PC12 cells through cell differentiation induction and cholinergic activities enhancement. These effects could be regulated by mitogen-activated protein kinase (MAPK), ERK1/2 signaling pathway. [Copyright &y& Elsevier]

Premna microphylla turcz is traditionally used as a folk remedy. Its roots, stems and leaves can be invoked as medicines, which have the functions of detoxification, swelling and hemostasis. It belongs to the Premna in the Verbenaceae and is mainly distributed in the mountains of southeastern China. However, there are few reports of in-depth studies on the anti-inflammatory effects of polysaccharide, which was the main component in Premna microphylla turcz. The flies were fed with standard corn flour-yeast medium to cause inflammation by sodium lauryl sulfate (SDS). The treatment group contained Premna microphylla turcz polysaccharide (pPMTLs) extract. The survival rate was obtained by feeding a vial containing five layers of filter paper, which was infiltrated with the 5% sucrose solution contaminated with SDS or SDS polysaccharide. The microvilli and nucleus of the midgut epithelial cells of different treatments were observed by transmission electron microscope, and the expression of inflammation-related genes was detected by real-time quantitative PCR (qRT-PCR). Finally, 16S rDNA analysis was conducted on the differences in the composition of the intestinal microbes of Drosophil a. In the current study, we showed that pPMTLs significantly prolonged the life span of SDS-inflamed flies from 5 days to 6 days. And pPMTLs reduced the rupture of microvilli in the midgut and restored the nuclear structure. In addition, pPMTLs significantly improved expression level of immune-related genes in Inflammation Drosophila especially the defensin (4.32 ± 0.75 vs 9.97 ± 0.52 SDS-polysaccharide group: SDS group, p < 0.001). The analysis of intestinal microbiota showed that pPMTLs decreased the relative abundance of Raoultella while Wolbachia increased (p < 0.05). Collectively, our results revealed the potential application of pPMTLs in enhancing inflammation defense, which would be enormous significance for the inflammation-related disorders treatment. • PMTLs polysaccharides showed excellent immunomodulatory activity in vivo. • Intestinal immunity was significantly enhanced by PMTLs polysaccharides. • Polysaccharides effectively reduced harmful intestinal bacteria. • Polysaccharides could significantly improve the expression of AMPs. [ABSTRACT FROM AUTHOR]

The traditional use of Prunella vulgaris is for the treatment of liver cancer in a few areas of China. At present, it is used primarily for the treatment of thyroid cancer, throat cancer, and lymphosarcoma among others. However, there are few current scientific reports regarding its use for the treatment of liver cancer. In this paper, the effective treatment for liver cancer is studied to provide an experimental basis for the application of Prunella vulgaris , which is related to preparations in the treatment of liver cancer. To study the anti-hepatocarcinoma effect of Prunella vulgaris total flavonoids and explores the possible molecular mechanism. The effects of Prunella vulgaris total flavonoids on the proliferation of SMMC-7721 cells were respected by RTCA analysis system. The tumor volume and weight were found in H22 tumor bearing mice. ELISA was used to observe the apoptosis and autophagy protein expressions in tumor tissue homogenate, along with the immune serum factor. Tumor tissue apoptosis was respected by the TUNEL method. And Bax, Bcl2, PI3K, Akt, mTOR, Beclin-1 and LC3-I/LC3-II expression were observed through Western blot. We also observed the expression of Beclin-1 and LC3-I/LC3-II through immunohistochemistry. The total flavonoids of Prunella vulgaris inhibited the activity of SMMC-7721 cells, and reduced the tumor volume and weight in H22 tumor bearing mice. HE staining showed that the Prunella vulgaris total flavonoids inhibited liver metastasis of H22 tumor. The Prunella vulgaris total flavonoids significantly made the expressions of IL-6, TNF-α and IFN-γ immune factors increasing in the serum of tumor bearing mice, and the contents of caspase-3 and caspase-9 increase as well in tumor tissue homogenate. TUNEL showed that the mean density in the intervention group was significantly higher than that in the control group. P62 content in tumor tissue homogenate increased and ATG5 decreased after intervention. Immunohistochemistry showed Beclin-1 expression decreased and LC3-I/LC3-II increased in the tumor tissue. Western blot showed Bcl2, Beclin-1 expression decreased and Bax, PI3K, Akt, mTOR, LC3-I/LC3-II increased in the tumor tissue. Prunella vulgaris total flavonoids have an obvious anti-hepatocarcinoma effect, and the mechanism may be linked to the inhibition of autophagy and promotion of apoptosis in liver cancer cells. The inhibition of autophagy may be related to activation of the PI3K/Akt/mTOR pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Shuang-Huang-Lian preparation has captured wide attention since its clinical applications for the successful treatment of upper respiratory tract infection. However, its functional basis under actual therapeutic dose in vivo was still unrevealed. This study aimed to reveal the anti-flu substances and mechanism of Shuang-Huang-Lian water extract (SHL) on H1N1 infected mouse model by a strategy based on serum pharmaco-chemistry under actual therapeutic dose and network pharmacology. H1N1 infected mouse model was employed for evaluation of the anti-flu effects of SHL. A simultaneous quantification method was developed by UPLC-TQ-XS MS coupled switch-ions mode and applied to characterize the pharmacokinetics of the multiple components of SHL under actual therapeutic dose. The potential active ingredients were screened out based on their pharmacokinetic parameters. And then, a compound mixture of these active candidates was re-evaluated for the anti-flu activity on H1N1 infected mouse model. Furthermore, the anti-flu mechanism of SHL was also predicted by network pharmacology coupled with the experimental result. SHL significantly increased the survival rate and prolonged survival days on H1N1 infected mice at a dosage of 20 g crude drug/kg/day by reversing the increased lung index, down-regulating the inflammatory cytokines (TNF-α, IL-1β, IL-6) and inhibiting the release of IFN-β in bronchoalveolar lavage fluids (BALF). Concomitantly, the pharmacokinetic parameters of fourteen quantified and twenty-one semi-quantified constituents of SHL were characterized. And then, five compounds (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin), which displayed satisfactory pharmacokinetic features, were considered as potential active ingredients. Thus, a mixture of these five ingredients was administered to H1N1-infected mice at a dose of 4.24 mg/kg/day. As a result, the therapeutical effects of the mixture were similar to SHL in terms of survival rate, lung index and the release of cytokines (TNF-α, IL-1β and IL-6) in BALF. Moreover, network pharmacology analysis indicated that the TNF-signal pathways might play a role in the anti-flu mechanism of SHL. A mixture of five compounds (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin) were the anti-flu substances of SHL. The strategy based on serum pharmaco-chemistry under actual therapeutic dose provided a new sight on exploring in vivo effective substances of TCM. Image 1 • A new strategy based on serum pharmaco-chemistry and network pharmacology was proposed and applied to explore anti-flu substances of SHL. • SHL showed significant anti-flu effects on H1N1 infected mice at a therapeutic dose (i.g. 20 g crude drug/kg/day). • Anti-flu effect of a mixture (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin) was similar to SHL. • Network pharmacology analysis indicated that the TNF-signal pathways might play a role in the anti-flu mechanism of SHL. • The new strategy proposed in this paper provided a new sight on exploring in vivo effective substances of TCM. [ABSTRACT FROM AUTHOR]

According to the theory of traditional Chinese medicine, the main pathogenesis of severe hand, foot and mouth disease (HFMD) is that the heat and wet poisons are deeply trapped in the viscera, which causes the deficiency of Qi and Yin in the patient's body. Ginsenoside Rb1 (Rb1) is the most abundant triterpenoid saponin in Panax quinquefolius L., which has the function of Qi-invigorating and Yin-nourishing. Enterovirus 71 (EV71) is one of the causative pathogens of HFMD, especially the form associated with some lethal complications. Therefore, the therapeutic effect of Rb1 on this disease caused by EV71 infection is worth exploring. We explored the effective antiviral activities of Rb1 against EV71 in vitro and in vivo and investigated its preliminary antiviral mechanisms. EV71-infected two-day-old suckling mice model was employed to detect the antiviral effects of Rb1 in vivo. To detect the antiviral effects of Rb1 in vitro, cytopathic effect (CPE) reduction assay was performed in EV71-infected Rhabdomyosarcoma (RD) cells. Interferon (IFN)-β interference experiment was employed to detect the antiviral mechanism of Rb1. In this paper, we first found that Rb1 exhibited strong antiviral activities in EV71-infected suckling mice when compared to those of ribavirin. Administration of Rb1 reduced the CPE of EV71-infected RD cells in a dose-dependent manner. Moreover, EV71-induced viral protein-1 (VP-1) expression was significantly reduced by Rb1 administration in vitro and in vivo. Furthermore, Rb1 treatment could induce high cellular and humoral immune responses in vivo. Meanwhile, Rb1 contributed to the enhanced Type I IFN responses and IFN-β knockdown reversed the antiviral activity of Rb1 in vitro. In summary, our findings suggest that Rb1 is an immune-stimulatory agent and provide an insight into therapeutic potentials of Rb1 for the treatment of EV71 infection. Image 1 [ABSTRACT FROM AUTHOR]

The history of medical application of propolis (also known as bee glue) dates back to the times of ancient Greeks, Romans, Persians and Egyptians. Honey and other bee products, including propolis, occupy an important place in Polish folk medicine. Scientific research on propolis in Poland began in the early 1960s in Zabrze and continues until now. The aim of this review is to provide an overview of information on Polish research on propolis and its medical application with particular emphasis on studies concerning wound healing. Consequently, our goal is also to shed a new light on therapeutic potential of Polish propolis in order to support future research in the field. A systematic review of scientific literature on propolis and its medical application was performed by using the literature databases (PubMed, Web of Science, Google Scholar). We paid special attention to papers describing the effect of propolis on skin wound healing as well as to Polish contribution to research on propolis. Professor Stan Scheller was the first Polish scientist dealing with propolis and its medical potential. His legacy was continued by several research teams that studied the topic in various aspects. They analyzed propolis composition, its antioxidant, anti-inflammatory, antimicrobial, antiapoptotic and anticancer properties as well as its application in dentistry and wound treatment. Burn wound healing physiology after propolis administration was thoroughly studied on pig model, whereas research on patients proved the efficacy of propolis in chronic venous leg ulcer treatment. Polish scientists have made a significant contribution to the research on propolis, its biological properties and influence on wound healing. Propolis ointments can effectively accelerate the healing process and improve healing physiology, so they can be recommended as a promising topical medication for wound treatment in the future clinical and preclinical trials. Image 1 [ABSTRACT FROM AUTHOR]

Chaihu-Longgu-Muli decoction (CLMD) is a well-known ancient formula in traditional Chinese medicine (TCM) to relieve disorder, clear away heat, tranquilize the mind and allay excitement. It has been used for the therapy of neuropsychiatric disorders such as epilepsy, dementia, insomnia, anxiety, and depression for several centuries in China. This paper is based on the assumption that the mechanism by which CLMD relieves epileptic symptoms in rats is associated with improving autophagy. Several experimental methods are designed to testify the hypothesis. The lithium-pilocarpine-induced epilepsy model was established in rats. The seizure frequency was recorded. Morphology and number of autophagosomes in hippocampal dentate gyrus was detected with a transmission electron microscope (TEM). Expression of Beclin-1, microtubule-associated proteins 1A/1B light chain 3 (LC3), and mammalian target of rapamycin (mTOR) in dentate gyrus was measured by immunofluorescence assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western-blotting. CLMD could significantly relieve the seizure frequency and improve autophagy in hippocampal dentate gyrus. Meanwhile, the level of Beclin-1 and LC3B decreased significantly, while mTOR increased remarkably after medical intervention. CLMD could improve autophagy in hippocampal dentate gyrus due to epilepsy, especially at high dose. The mechanism may be related to upregulated expression of mTOR and downregulated expression of Beclin-1 and LC3B. Image 1 [ABSTRACT FROM AUTHOR]

Reduning injection (RDN), a patented traditional Chinese medicine, has the obvious antipyretic effect and has been widely used in China. Although some previous studies proved its antipyretic effect by animal efficacy experiment or clinical observation, its holistic mechanism in vivo was still unclear. To comprehensively elucidate the antipyretic mechanism of RDN, the investigation of fever-related potential biomarkers and metabolic pathways in the rat fever model is described in this paper. Rat fever model was established by dry yeast. A large number of endogenous metabolites in serum and urine were detected by UPLC-Q-TOF/MS, and fever-related potential biomarkers were screened and identified by multivariate analysis and metabolite databases. The reliability and biological significance of the largely disturbed biomarkers was verified by the metabolic network and the correlation with pharmacodynamic indicators, which contained IL-1β, IL-6, TNF-α, PGE 2 and cAMP. The established UPLC-Q-TOF/MS analytical method afforded satisfactory results in terms of precision, repeatability and stability, which met the requirements of biological sample determination. A total of 32 potential biomarkers associated with fever were screened and identified, among which 22 species could be adjusted by RDN. The metabolism pathway analysis revealed that valine, leucine and isoleucine biosynthesis, and sphingolipid metabolism were greatly disturbed. Their biomarkers involved L-leucine, L-valine, sphinganine and phytosphingosine, all of which showed a callback trend after RDN was given. These 4 biomarkers had a certain correlation with some known fever-related small molecules and pharmacodynamic indicators, which indicated that the selected fever-related biomarkers had certain reliability and biological significance. RDN has a good regulation of the metabolic disorder of endogenous components in dry yeast-induced fever rats. Its antipyretic mechanism is mainly related to the regulation of amino acid, lipid and energy metabolism. The study is useful to better understand and analyze the pharmacodynamic mechanism of complex systems, such as traditional Chinese medicine. Image 1 [ABSTRACT FROM AUTHOR]

BabaoDan (BBD) is a famous traditional Chinese formula frequently used in TCM clinics to eliminate jaundice and treat infectious viral hepatitis. This paper assesses BBD's preventive and therapeutic effects on hepatic encephalopathy after liver cirrhosis (CHE) and acute liver failure (AHE) in rats and explains its possible mechanism of action. CHE rat model was established by injection of carbon tetrachloride (CCl4) twice a week for a total of 9 weeks and then by injection of thioacetamide (TAA) to induce hepatic encephalopathy. AHE rat model was established by injection of TAA once a day for a total of 3 days. In CHE rat model, BBD was gavaged once a day at the end of the 6th week until the experiment ended. In AHE rat model,BBD was gavaged once a day 3 days before TAA injection until the experiment ended. The preventive and therapeutic effects of BBD on brain dysfunction, as well as liver injury, pathology and fibrosis were evaluated in vivo. The role of BBD in the regulation of inflammatory factors and myeloid differentiation factor 88/Toll-like receptor 4/nuclear factor kappa-B (TLR4/MyD88/NK-κ B) pathway was detected in both liver and brain in vivo. The rat bone marrow derived macrophages (BMDMs) were activated by Lipopolysaccharide (LPS), and the role of BBD in the regulation of inflammatory factors and NK-κ B pathway were detected in vitro. In CHE rat model: BBD significantly improved the total distance as well as the activity rate of rats. BBD also improved the learning and memory abilities of rats compared with the control group. In addition, BBD effectively decreased ammonia levels and significantly decreased the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and total bile acid (TBA), as well as improved the levels of total protein (TP) and albumin (Alb). In the liver, BBD not only inhibited the gene expressions of tumor necrosis factor alpha (TNF-α), interleukini-6 (IL-6), TLR4, MyD88, and NF-κ B but also inhibited the protein expressions of TLR4, MyD88, NK-κ B and TNF-α. In the brain, BBD inhibited the gene expressions of iNOS, IL-6, TNF-α, TLR-4, MyD88, and NF-κ B, as well as inhibited the protein expressions of TLR4, MyD88, P65 TNF-α and ionized calcium binding adapter molecule 1 (Iba-1). BBD also decreased NO and TNF-α in the blood. BBD improved neurological scores, blood ammonia levels and the brain inflammatory gene expressions of iNOS, TNF-α and IL-1β. BBD also improved liver function biomarkers such as ALT, TBil, TBA, TP, ALB and inflammatory and apoptotic gene expressions of TNF-α, IL-1β, IL-6, Bax, Bcl-2, caspase-9, caspase-3 and NF-κ B. In LPS-activated rat BMDMs, BBD decreased NO and TNF-α production in BMDM culture supernatant. In addition, BBD inhibited the gene expressions of TNF-α, IL-1 β and IL-6 as well as the phosphorylation of P65. BBD can prevent and cure hepatic encephalopathy (HE) derived from both chronic and acute liver diseases. BBD can reduce hyperammonemia as well as the systematic and neurological inflammation. Inflammation is likely an important target of BBD to treat HE. The anti-inflammatory role of BBD may lie in its regulation of the TLR4/MyD88/NF-κ B pathways. Image 1 [ABSTRACT FROM AUTHOR]

The use of herbal medicines is increasing in developed countries as alternative and/or supportive therapy to conventional health care medicines. Malva neglecta Wallr. (Family: Malvaceae) has been reported as wound healing remedy in traditional medicines, however no experimental data is available on its wound healing potentials. The aim of this study was to explore phytochemistry and validate wound healing potentials of the plant using animal models. M. neglecta crude methanolic extract (Mn.Cme) was chemically characterized using HPLC-DAD and GCMS analysis. Acute dermal toxicity was determined in albino rats following Organization of Economic Co-operation and Development (OECD) 402 established standards. Wound healing potentials were evaluated in rats using excision wound model. Wounds (177 mm2) were made by an excision on the skin of rats which were placed individually in cages. Mn.Cme was formulated in ointment form and was applied topically onto the wound area once daily for 14 days. The wound area was measured with translucent paper and thereafter estimated on a 1 mm2 graph sheet every 3rd day until epithelialization and complete wound closure was recorded. Wound contraction was calculated as a percentage of the original wound size. Antioxidant potentials were also evaluated via FRAP, DPPH and H 2 O 2 free radicals scavenging assays. HPLC-DAD analysis revealed 25 phenolic compounds with higher amounts of hydrotyrosol (109.3 mg/g), coumaroylhexoside (97.4 mg/g), kaempferol-3-(p-coumaroyldiglucoside)-7-glucoside (37.2 mg/g), quercetin-3- O -rutinoside (31.5 mg/g) and epicatechin-3- O -(4- O -methyl)-gallate (31.3 mg/g). In GC-MS analysis, oleic acid (19.67%), taurine (17.60%), ethylene dimercaptan (14.67%), isoeugenol (14.61%), patchoulane (10.36%), methyl 12-methyltetradecanoate (8.47%) and isopropyl myristate (7.02%) were highly abundant compounds. No sign of toxicity was observed in the acute dermal toxicity test. Our test sample (Mn.Cme) exhibited considerable wound healing tendency at all doses (1 g, 1.5 g, 2 g per 10 g of ointment base) with reduced epithelialization period in a dose–related manner. Absolute healing was observed after application of 2 g of Mn.Cme ointment. Further, Mn.Cme exhibited considerable anti-radical potential in all assays. It may be concluded that M. neglecta possess very potent secondary metabolites which are previously reported for wound healing potentials. The plant has considerable antioxidant and wound healing properties and thus warrant further studies to uncover the molecular mechanism its wound healing potentials. Image 1 [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-β/Smads pathway. We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10 mg/kg/d) and Astragalus extract (AE) (4.35 g/kg/d, which contained about ASG 10 mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 μM) and treated with ASG (10 μM) simultaneously for 24 h. The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-β/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-β/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis. AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-β/Smads pathway. Image 1 [ABSTRACT FROM AUTHOR]