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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]

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]

Licorice can nourish Pi (spleen) and thereby strengthening the digestive system according to the theory of traditional Chinese medicine. Licorice has been generally used in the compound prescription to treat intestinal inflammatory disease. Licochalcone A (Lico A) is one of the characteristic molecules from licorice. T-UCRs, which are transcribed from ultraconserved regions, are a new class of long noncoding RNAs related to the renewal of intestinal epithelial renewal. This study aimed to investigate the effect and the uc.173-related mechanism of Lico A on intestinal epithelial renewal. IE-6 and Caco-2 cells were used to evaluate the effect of Lico A on apoptosis, proliferation, and migration of IECs. The intestinal organoid was used to investigate ex vivo effect and mechanism of Lico A promoting intestinal organoid development. C57BL/6J mice (both normal and uc.173-deficient ones) were used to examine the in vivo effect of Lico A on the renewal of intestinal mucosa. The expression of three T-UCRs related to the intestinal mucosa renewal was altered in Lico A-treated IECs. Lico A promoted the proliferation and inhibited the apoptosis of IECs through uc.173/miR-195 pathway. The development of intestinal organoids and the renewal of intestinal mucosa of mice subjected to the 48-h FAST were all promoted by the treatment of Lico A. Moreover, the growth arrest of uc.173-deficient intestinal organoids and the atrophy of intestinal mucosa in uc.173-deficient mice could be rescued by the Lico A administration. Results in this paper suggest that targeting T-UCRs may be the novel therapeutic approach for the promotion of epithelial regeneration, and through stimulating the regeneration of intestinal mucosa, Lico A may become a new therapeutic agent for the maintenance of intestinal epithelial integrity. Licochalcone A promotes intestinal epithelial renewal through uc.173. [Display omitted] • Licochalcone A from licorice affects the expression of three T-UCRs related to the regeneration of intestinal mucosa. • Licochalcone A promotes the development of intestinal organoids and in vivo renewal of intestinal mucosa. • Licochalcone A reverses uc. 173-induced delay in intestinal epithelial renewal both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ximenia caffra Sond. (Ximeniaceae), commonly known as “sour plum” is traditionally used, both topically and orally to treat a wide range of human diseases and ailments such as wounds, sexually transmitted infections (STIs), infertility, stomach ache, fever, eye problems, diarrhoea, bilharzia, menorrhagia, malaria, intestinal worms, impotence and coughs. The bark and fruits are used by small-scale farmers as ethnoveterinary medicine to treat dermatophilosis, foot rot, saddle sores and control ectoparasites. Oil from X. caffra seed is traditionally used as a moisturiser, soap and shampoo for dry, fragile and damaged hair. Aim of the review The aim of this study was to comprehensively summarize the research that has been done on the botany, ethnomedicinal uses, phytochemistry and biological activities of X. caffra in different locations throughout its geographical range in the sub-Saharan African region so as to understand its importance and potential in primary healthcare systems. Materials and methods This study was carried out using a comprehensive and systematic literature search on the ethnomedicinal uses, phytochemistry and biological activities of the species throughout its distributional range. Literature sources included papers published in international journals, reports from international, regional and national organizations, conference papers, books and theses. PubMed and Scopus, search engines such as Google Scholar and online collection ScienceDirect were used. Results This study showed that X. caffra is used as traditional medicine in 83.3% of the countries in tropical Africa where it is indigenous. A total of 65 human and animal ailments and diseases are recorded for X. caffra, with a high degree of consensus for wounds, sexually transmitted infections (STIs), infertility, stomach ache, fever, eye problems, diarrhoea, bilharzia, menorrhagia, malaria, intestinal worms and coughs. Phytochemical investigation of X. caffra revealed that the species has various compounds including flavonoids, phenols, phytosterols, tannins and fatty acids. Different plant parts, aqueous and organic extracts exhibited anti-amoebic, antibacterial, antifungal, anti-inflammatory, antioxidant, antiparasitic, antiproliferative, HIV-1 reverse transcriptase (RT) inhibitory, insecticidal, non-mutagenic and toxicity activities. Conclusion In this review, the ethnomedicinal uses, phytochemistry, biological activities and toxicity of different extracts and compounds of X. caffra have been summarized. Although many of the ethnomedicinal uses of X. caffra have been validated by phytochemical and pharmacological studies, there are still some gaps where current knowledge could be improved. There are very few to nil experimental animal studies, randomized clinical trials and target-organ toxicity studies involving X. caffra and its derivatives that have been carried out so far. At the present moment, there is not sufficient evidence to interpret the specific chemical mechanisms associated with some of the documented biological activities of the species. Therefore, future studies should identify the bioactive components, details of the molecular modes or mechanisms of action, pharmacokinetics and physiological pathways for specific bioactives of X. caffra . [ABSTRACT FROM AUTHOR]

Duhuo Jisheng decoction is a traditional Chinese formula that has been widely used in clinical practice to treat osteoarthritis, which has the effects of removing invaded cold and dampness, relieving joint pain. However, it is difficult to determine the effective substances and mechanisms due to assorted herbs and components, and further research is needed. This study was designed to explore and verify the mechanism and targets of DHJSD in the treatment of OA via network analysis and experiments. In this study, the active ingredients of DHJSD were qualitatively analyzed by UPLC-QDA. Network analysis was used to identify common targets and pathways. Next, we explored the therapeutic mechanism of DHJSD through a rat model of knee osteoarthritis. HE staining was used to judge the establishment of the animal model. ELISA and Western blotting were used to verify the expression of key pathway proteins. In this study, seventeen chemical constituents in DHJSD were identified. According to the network analysis, we obtained the potential associated pathways of action. Then, molecular docking and SPR experiments showed that the sixteen identified components had high binding energies to IL-6. HE staining showed that the high-dose group of DHJSD had an obvious therapeutic effect on model rats. Compared with the model group, the levels of IL-1β, TNF-α, IL-6, MMP3, MMP13, ADAMTS4 and ADAMTS5 in serum and the expression of STAT3 and p-STAT3 protein in administration groups were significantly decreased. This result indicated that the IL-6/STAT3 signaling pathway was one of the important pathways regulated by DHJSD to improve OA. [Display omitted] • This paper first identified 17 compounds, found that DHJSD can treat OA by regulating IL-6/STAT3 pathway in vivo. [ABSTRACT FROM AUTHOR]

Ligusticum chuanxiong Hort. (Chuanxiong, LC), as an important traditional Chinese medicine (TCM), can not only be used as a monarch herb but also be used as a classic "Yin-Jing" (引经) medicine in compound prescriptions, e.g., Buyang Huanwu Decoction (BHD). Although LC has the effect of guiding components into the brain in BHD, there is still a lack of scientific evidence on this "Yin-Jing" effects. Herein, we used pharmacokinetics and tissue distributions to investigate "Yin-Jing" effects of LC. To simplify the study, four major constituents in BHD, i.e., Calycosin (CA), astragaloside IV (AI), paeoniflorin (PA), and amygdalin (AM) were combined to form a simple compound (abbreviated as CAPA here) to replace the original BHD in this paper. The Yin-Jing medical property of LC was confirmed by the compatibility of CAPA with LC or its different fractions (Fr. A ∼ Fr. F). To explore the "Yin-Jing" medical property of LC via pharmacokinetics and tissue distributions by ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS). The contents of CA, AI, PA, and AM were simultaneously determined by the established and validated UPLC-QQQ-MS method in different rat tissues and plasma after administration of CAPA with the combination of LC or Fr. A ∼ Fr. F. The pharmacokinetic parameters, e.g., T max , C max , AUC 0–t and MRT 0–t , were calculated to evaluate the efficiency of "Yin-Jing". The C max and AUC 0–t of CA, AI, PA, and AM were remarkably increased in rat brain tissues compared with those of the control group after compatibility of LC. This demonstrated that LC has the Yin-Jing effects on brain tissues. Additionally, Fr. B or Fr. C might be the material basis by specifically studying the distributions of CA, AI, PA, and AM in brain tissue based on mutual compatibility. The effects of Fr. B and Fr. C on distributions of these constituents in other tissues or plasma was also studied to verify the effects of Yin-Jing of LC. The results showed that the same upward trend is found in heart, liver and plasma, but the intensity is insignificant as that in brain tissue. Furthermore, the C max and AUC 0–t of some analytes in the rat spleen, lung, and kidney were significantly decreased compared with the control group (P < 0.05 or 0.01). LC has the function of Yin-Jing, especially guiding the components into the brain tissue. Moreover, Fr. B and Fr. C is suggested to be the pharmacodynamic material basis for the effect of Yin-Jing of LC. These finding explained that it was recommended to add LC into some prescriptions for treating cardiovascular and cerebrovascular diseases caused by Qi deficiency and blood stasis. This has laid a certain foundation for the research on the Yin-Jing efficacy of LC to better clarify the theory of TCM and guide the clinical application of Yin-Jing drugs. [Display omitted] • To explore the Yin-Jing property of LC by pharmacokinetics and tissue distribution. • A UPLC-MS method was established for the determination of analytes in rat tissues and plasma. • LC has the Yin-Jing function, particularly guiding components into the brain. • Fr. B or Fr. C maybe the material basis of LC for its Yin-Jing efficacy. [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 There are insufficient safe and effective treatments for chronic pain in pets. In cases such as osteoarthritis there is no commercially available cure and veterinarians use NSAIDs to manage pain. Pet owners may have to plan for a lifetime of plant-based treatment for the conditions that lead to chronic pain in pets. Phytopharmacotherapies have the advantage of being less toxic, cheap or free, readily available, are more likely to be safe for long-term use and have the potential to reset the immune system to normal functioning. Aim of the study To examine the recently published medicinal plant research that matches unpublished data on ethnoveterinary medicines (EVM) used for pets in Canada (British Columbia) to see if the EVM data can provide a lead to the development of necessary drugs. Materials and methods In 2003 semi-structured interviews were conducted with 60 participants who were organic farmers or holisitic medicinal/veterinary practitioners obtained using a purposive sample. A draft manual prepared from the data was then evaluated by participants at a participatory workshop that discussed the plant-based treatments. A copy of the final version of the manual was given to all research participants. In 2018, the recently published research matching the EVM data was reviewed to see if the EVM practices could serve as a lead for further research. Results and conclusion Medicinal plants are used to treat a range of conditions. The injuries treated in pets in British Columbia included abscesses (resulting from an initial injury), sprains and abrasions. Dogs were also treated with medicinal plants for rheumatoid arthritis, joint pain and articular cartilage injuries. More than 40 plants were used. Anal gland problems were treated with Allium sativum L., Aloe vera L., Calendula officinalis L., Plantago major L., Ulmus fulva Michx., Urtica dioica L. and Usnea longissima Ach. Arctium lappa , Hydrangea arborescens and Lactuca muralis were used for rheumatoid arthritis and joint pain in pets. Asthma was treated with: Linum usitatissimum L., Borago officinalis L., Verbascum thapsus L., Cucurbita pepo L., Lobelia inflata L., and Zingiber officinale Roscoe. Pets with heart problems were treated with Crataegus oxyacantha L., Cedronella canariensis (L.) Willd. ex Webb & Berth, Equisetum palustre L., Cypripedium calceolus L., Pinus ponderosa Douglas ex Lawson, Humulus lupulus L., Valeriana officinalis L., Lobelia inflata L., Stachys officinalis (L.) Trev., and Viscum album L. The following plants were used for epilepsy, motion sickness and anxiety- Avena sativa L., Valeriana officinalis , Lactuca muralis (L.) Fresen., Scutellaria lateriflora L., Satureja hortensis L., and Passiflora incarnata L. Plants used for cancer treatment included Phytolacca decandra , Ganoderma lucidum , Lentinula edodes , Rumex acetosella , Arctium lappa , Ulmus fulva , Rheum palmatum , Frangula purshiana , Zingiber officinale , Glycyrrhiza glabra , Ulmus fulva , Althea officinalis , Rheum palmatum , Rumex crispus and Plantago psyllium. Trifolium pratense was used for tumours in the prostate gland. Also used were Artemisia annua , Taraxacum officinale and Rumex crispu s. This review of plants used in EVM was possible because phytotherapy research of the plants described in this paper has continued because few new pharmaceutical drugs have been developed for chronic pain and because treatments like glucocorticoid therapy do not heal. Phytotherapuetic products are also being investigated to address the overuse of antibiotics. There have also been recent studies conducted on plant-based functional foods and health supplements for pets, however there are still gaps in the knowledge base for the plants Stillingia sylvatica , Verbascum thapsus , Yucca schidigera and Iris versicolor and these need further investigation. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Pulsatilla chinensis (Bunge) Regel is a valuable traditional Chinese medicine (TCM) which is widely used for the treatment of schistosomiasis, inflammatory, bacterial infections. In recent years, P chinensis has been reported to exhibit antitumor activities. However, the mechanisms underlying its toxic effects remain largely unresolved. This paper is designed to investigate the damage of long-term oral P. chinensis saponins (PRS) and to explore its potential damage mechanisms by serum metabonomics approach. Materials and methods The serum samples from control and PRS treated rats were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) in positive ionization mode and negative ionization mode. Liver function index of ALT, AST and ALP, blood biochemistry and biomarkers were examined to identify specific changes of injury. Acquired data were subjected to principal component analysis (PCA) for differentiating the control and PRS treated groups. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after PRS treated and further integration of metabolic networks. Results The results suggested that serum liver function indexes of ALT had significantly changed and stage increased. AST, ALP detection content show volatility changes. Changes in the 15 biomarkers found in the serum, such as acetaminophen glucuronide, 9 E, 11 E-linoleic acid, chenodeoxycholic acid, monoacylglycerides, sphingomyelin (SM), 7-ketodeoxycholic acid and 12-keto-deoxycholic acid, which were closely related to changes in liver injury. It could be seen clearly that with the change of the dosing time, the biomarkers in the serum have undergone obvious, regular and progressive changes through the score plot and corresponding loading plot. The underlying regulations of PRS-perturbed metabolic pathways were discussed according to the identified metabolites. Conclusion The present study proves the potential of UPLC-QTOF-MS based metabonomics in mapping metabolic response. Long-term oral administration of P. chinensis saponins can cause chronic liver injury, and its safety needs further attention. It is of great significance in safeguarding human health to explore the damage mechanism of Pulsatilla chinensis saponins on liver by serum metabolomics. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Involucrum castaneae (IC)is used in Chinese folk medicine to treat various lung diseases, as well as for its reducing phlegm and anti-inflammatory properties. Aim of the study The purpose of this experiment is to verify the effect of IC on airway inflammation, responsiveness in ovalbumin (OVA)-induced asthmatic guinea pigs. The main chemical components of IC were also analyzed. Materials and methods The potential of the ethanol extract of Involucrum castaneae (EEIC) to protect against OVA-induced allergic airway response in guinea pigs was investigated. The latency of asthma in guinea pigs were recorded after the allergic asthma induced. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of immunoglobulin E (IgE), interleukin-5 (IL-5), nerve growth factor (NGF) and interferon-γ (IFN-γ) in asthma allergy. Reverse transcription-PCR (RT-PCR) was used to detect the expression of IL-5 mRNA in asthmatic guinea pig lungs. Paraffin sections of lung tissue were used to analyze pathological changes. The total flavonoid content was determined and the chemical components were analyzed by LC-MS/MS. Results It was found that EEIC was able to reduce the number of eosinophil (EOS) in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) in the guinea pig model of OVA -induced asthma. Meanwhile, it also significantly reduced the levels of inflammation-related factors IgE and IL-5, decreased the expression of IL-5 mRNA in lung tissue, and increased the level of IFN-γ. Pathological examination of paraffin section of lung tissue showed that EEIC can reduce the thickening of bronchial smooth muscle and reduce the infiltration damage of tissues by various inflammatory cells. The presence of flavonoids, terpenoids and phenolic compounds in EEIC might be responsible for these activities. Conclusion IC alleviated airway inflammation and smooth muscle thickening in guinea pigs with OVA-sensitized allergic asthma. The paper explains the traditional efficacy and material basis of IC and lays a foundation for further development. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

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]

Vinegar-baked Radix Bupleuri (VBRB) is usually used to focus other drugs effect on liver in traditional Chinese medicine (TCM). However, no sufficient scientific data are available to support this concept. In this paper, the liver targeting enhancing effect of VBRB on rhein was investigated. 432 of rats were divided into two large groups according to the dose of rhein, low dose group of rhein (LDGR) and high dose group of rhein (HDGR). In each group, the rats were further divided into four subgroups, rhein control and rhein co-administered with three different doses of VBRB peroral. Concentrations of rhein and its metabolite in different tissues were determined by HPLC. Compared to the control group, VBRB significantly increased the distribution of both rhein and its metabolite in liver and meanwhile decreased their distribution in other tissues, indicating a strong liver targeting enhancing effect. This liver targeting effect of VBRB depended on the dose of VBRB and rhein. Low and high dose of VBRB had a more strong effect than medium dose in HDGR; high dose of rhein was more sensitive than low dose of rhein (P <0.05). Rhein existed in two forms after peroral administration in vivo. It was found that the liver targeting effect of VBRB was more remarkable with the native form of rhein compared to its derivative form. The results of this paper demonstrated that co-administration with VBRB is a simple and efficiencient method for liver targeting therapy, and the meridine guide theory of TCM was credible. [Copyright &y& Elsevier]

Exocarpium Citri grandis (ECG, Huajuhong in Chinese), the epicarp of C. grandis 'Tomentosa', has been used for hundreds of years as an anti-inflammatory, expectorant, hypoglycemic, and lipid-lowering medication in China. Nevertheless, there have been few papers that have explored the mechanism behind ECG's hypolipidemic characteristics from the perspective of treating nonalcoholic fatty liver disease (NAFLD). The purpose of our study was to confirm the therapeutic and preventative effects of ECG in NAFLD by regulating lipid accumulation and iron metabolism, and to explore the specific mechanism of ECG in enhancing hepatic iron transport and excretion capabilities. We constructed a NAFLD model by feeding male C57BL/6 J mice with a high-fat diet for 12 weeks. Mice were gavaged with ECG beginning in the seventh week of modeling, and three dosage gradients were established: low dose group (2.5 g/kg/d), medium dose group (5 g/kg/d) y, and high dose group (10 g/kg/d) until the end of model construction in week 12. We used network pharmacology to analyze the relationship between ECG and NAFLD. In addition, we constructed a nonalcoholic fatty liver disease model by feeding male C57BL/6 J mice a high-fat diet for 12 weeks. Finally, lipid accumulation, iron accumulation, inflammation and oxidative stress were evaluated by serological index detection, histological detection, immunofluorescent and immunohistochemical staining, and western blotting. Network pharmacology confirmed the treatment effect of ECG in NAFLD. Three active components of ECG, including Naringenin, Naringin and Neohesperidin, were detected by UHPLC-HRMS analysis. The results of serum TC, TG, LDL concentration, HE staining, Oil red staining and Nile red staining demonstrated that ECG could improve lipid metabolism disorders. The results of serum iron concentration, liver tissue iron concentration, iron metabolism-related proteins Ferritin light chain, Ferroportin1, Transferrin receptor, and Transferrin demonstrated that ECG improved the iron transport and storage capacities of hepatic cells. Our results demonstrated that ECG relieved liver injury by inhibiting lipid accumulation and iron accumulation in NAFLD. [Display omitted] • Exocarpium Citri Grandis reduces liver lipids accumulation and relieves liver damage in NAFLD. • Exocarpium Citri Grandis down-regulates hepatic iron intake by inhibiting TF/TfR pathway. • Exocarpium Citri Grandis is beneficial to the liver iron excretion and storage in NAFLD. [ABSTRACT FROM AUTHOR]

The roots of Achyranthes bidentata Blume are one of the regularly used herbal drugs in Chinese medicine, and has been applied for strengthening the muscle and bone for a long time. However, its effect on muscle remains unclear. This paper aims to explore the anti-muscle atrophy effect of A. bidentata , and to clarify the possible signaling pathways involved. The saponin extract of the roots of A. bidentata (ABSE) was prepared and analyzed, and its activity on myoblast differentiation was assayed with C2C12 cell culture. ABSE was then orally administered at dosage of 35, 70 and 140 mg/kg/day to disuse-induced muscle atrophy mice. The studies on mice body weight and muscle quality were conducted, and Western blot was used for exploring the possible signaling pathways involved in the muscle protective action aided with transcriptome analysis. The total saponin content of ABSE was 59.1%. ABSE promoted the C2C12 cells differentiation to myotube in C2C12 differentiation assay. Further study with disuse-induced muscle atrophy mice model demonstrated that ABSE significantly increased muscle fiber diameter as well as the proportion of slow muscle fibers. Possible mechanism study aided with transcriptome analysis revealed that ABSE alleviated muscle atrophy at least through activation of PI3K/Akt pathway in vivo & vitro. The saponin extract of the root of A. bidentata (ABSE) has a protective effect on muscle atrophy, and showed a considerable potential in prevention and treatment of muscle atrophy. [Display omitted] • The saponin extract of A. bidentata (ABSE) was prepared and analyzed. • ABSE promoted the differentiation of C2C12 cells to myotubes. • ABSE displayed a protective effect on muscle atrophy in vivo. • ABSE activated PI3K/Akt pathway in vivo & in vitro. • ABSE increased protein levels of Myogenin and MyoD. [ABSTRACT FROM AUTHOR]

Naru-3 is a prescribed formulation based on the theory of Mongolian medicine for the treatment of rheumatoid arthritis (RA). Naru-3 consists of three medicinal agents: Aconitum kusnezoffii Reichb (caowu), Terminalia chebula Retz (hezi), and Piper longum L (biba). These medicinal agents are widely distributed in the Mongolian area of China and have been used to treat rheumatism for centuries. Mongolian medicine Naru-3 is commonly prescribed to treat RA, but its mechanism of action is unknown. A rat collagen-induced arthritis (CIA) model was established to investigate the mechanism of Naru-3. Rats were treated with Naru-3, Etanercept (ETN), and sodium carboxymethylcellulose (CMC) for four weeks. After treatment was terminated, paw thickness, ankle diameter, and arthritis index (AI) were scored. Synovial hyperplasia was evaluated using hematoxylin and eosin (H&E) staining and two-dimensional ultrasonography. Synovitis and neovascularization were assayed using power Doppler imaging (PDI) and contrast-enhanced ultrasonography (CEUS). Levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1, and CD31 in the serum or synovium were detected using ELISA and immunohistochemistry analyses. Naru-3 and ETN alleviated the symptoms of CIA as evidenced by diminished paw thickness, ankle diameter, and AI scores. Mechanistically, Naru-3 inhibited synovial hyperplasia, synovitis, and neovascularization by diminishing systemic and local inflammation, as indicated by the relative expression of CD31, VEGF and IL-1 in the serumor synovium. After four weeks of treatment, no significant neovascularization was observed in the Naru-3 group, but neovascularization and synovitis occurred in the ETN group, as demonstrated by H&E staining, PDI, and CEUS examination. Naru-3 inhibited inflammation, synovial hyperplasia, and neovascularization and alleviates RA in our CIA rat model. No symptom recurrence was observed four weeks after drug treatment. [Display omitted] • This paper illustrats the mechanisms of action of Naru-3 in the treatment of RA through inhibition of synovial neovascularization. • No symptom recurrence is observed four weeks after Naru-3 treatment. • CEUS for evaluating synovial neovascularization provides reference for clinical visualization evaluation of drug efficacy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aloysia citrodora Paláu ( Lippia citriodora Kunth), commonly known as "lemon verbena" is a medicinal plant native to South America, North Africa, and South of Europe which is used by native people for several indications such as diarrhea, flatulence, insomnia, and rheumatism. Aim of the review Despite the wide biological activities of lemon verbena, there is no current review summarizing medicinal properties of the plant; thus, this paper aims to discuss current state of the art regarding the phytochemistry, pharmacology, and therapeutic applications of A. citrodora considering in vitro , in vivo , and clinical studies. Materials and methods Electronic databases including PubMed, Scifinder, Cochrane library, Scopus, and Science direct were searched with the scientific name of the plant and its synonyms, as well as the common name. All studies on the ethnobotany, phytochemistry, pharmacology, and clinical application of the plant until October 2017 were included in this review. Results Despite the few number of studies on the ethnopharmacology of the plant, A. citrodora is widely assessed regarding its phytochemistry and biological activities. Neral and geranial are the main ingredients of the essential oil; whereas verbascoside is the most significant component of the extract. Biological activities such as antioxidant, anxiolytic, neuroprotective, anticancer, anesthetic, antimicrobial, and sedative effects are proved in cell cultures, as well as animal studies. Conclusions Several pharmacological activities have been reported for A. citrodora ; however, the plant is not fully assessed regarding its safety and efficacy in human. Future well-designed human studies are essential to confirm the therapeutic benefits of this plant in clinical settings. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Copaifera species are used in folk medicine for a wide variety of pharmacological properties. This paper reports the cytotoxic and genotoxic analyses of oleoresins and leaves extracts of Copaifera species: C. duckei , C. multijuga , C. paupera , C. pubiflora, C. reticulata and C. trapezifolia . Materials and methods In vitro assays were performed using Chinese hamster lung fibroblasts (V79 cells). The clonogenic efficiency and cytokinesis-block micronucleus assays were employed for the cytotoxicity and genotoxicity assessment, respectively. The mouse bone marrow micronucleus test was used for in vivo studies. Results The cytotoxicity results using the clonogenic efficiency assay showed IC 50 values ranging from 9.8 to 99.2 µg/mL for oleoresins and 66.4–721.5 for leaves extracts. However, no cytotoxic effect was observed in the in vivo studies. Additionally, the treatments with oleoresins and leaves extracts did not significantly increase the frequency of micronuclei in both in vitro and in vivo mammalian cells. The UPLC-MS/MS and CG/MS analyses of Copaifera oleoresins allowed the identification of 10 acid diterpenes and 11 major volatile sesquiterpenes. Leaves are rich in phenolic compounds including two flavonoid heterosides and 16 galloylquinic acid derivatives. Conclusions The oleoresins and leaves extracts of studied Copaifera species were not cytotoxic in vivo, as well as not genotoxic in both in vitro and vivo assays, under the experimental conditions used. Therefore, the obtained results should be sufficient to demonstrate the absence of significant genotoxic risk of these Copaifera products for human use in the evaluated concentrations range. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Alpinae Oxyphyllae Fructus (AOF) with warming and tonifying the kidney and spleen, anti-salivation, anti-polyuria and anti-diarrhea functions is the dried ripe fruits of Alpinia oxyphylla Miq. (Zingiberaceae). As a traditional Chinese medicine, its application history is very long. Aims of the study The purpose of our study is to investigate the effects of different solvent extracts from AOF on lipopolysaccharide (LPS)-induced animal model of Alzheimer's disease (AD) to elucidate the traditional medical theories with modern pharmacological methods and provide a reference for further clarifying its active components and mechanisms. Materials and methods The method of stepwise screening was adopted in this paper. The animals were divided into 9 groups, including control (CT) group, model (MD) group, donepezil (DPZ) group, total extract (TT) group, petroleum ether extract (PE) group, chloroform extract (CF) group, ethyl acetate extract (EA) group, n-butanol extract (NB) group and water extract (WT) group. The anti-amnesic effects of different solvent extracts from AOF were measured in LPS-induced memory deficits mice by Y maze test and Morris water maze (MWM) test. Hematoxylin eosin (HE) staining was applied to observe pathological changes in hippocampus and cerebral cortex tissue of different groups. Biochemical indicators including ionized calcium-binding adaptor molecule 1 (IBA-1), interleukin beta 1 (IL-1β), Aβ 1–42 and hyperphosphorylated tau proteins (p-tau) in hippocampus and cortex after treatment with LPS were measured according to the manufacturer's instructions of ELISA kits. HPLC was used to evaluate the major components of different extracts. Results It was found that successive intragastric administration of AOF (360 mg/kg) extracts for 14 days showed different degrees of improvement on LPS-induced AD model as measured by Y-maze test, Morris water maze test , and Histopathological examination. Moreover, the results of ELISA suggested petroleum ether (PE) extracts were worth recommending for inhibiting the high level of IBA-1, IL-1β, Aβ 1–42 and p-tau in hippocampus and cortex after treatment with LPS. Conclusions The present study demonstrated for the first time that AOF attenuated LPS-induced learning and memory impairment, which may be associated with its inhibitory effect on neuroinflammation, amyloids-β (Aβ) deposition and p-tau. This research provided a theoretical basis for elucidating the traditional theory of AOF, and was also the stepping stone to the next step. [ABSTRACT FROM AUTHOR]

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 Metabolomics is the comprehensive assessment of endogenous metabolites of a biological system in a holistic context, and its property consists with the global view of Traditional Chinese Medicine (TCM). Shuihonghuazi Formula (SHHZF) has been used for liver cancer early treatment in clinical for more than thirty years, but its mechanism remains unclear completely. This paper was designed to explore the therapeutic effects of SHHZF on liver cancer and its metabolomic characters. Materials and methods All the rats were given diethylnitrosamine (DEN) at the dosage of 70 mg/kg for 14 weeks. From the 7th weeks, SHHZF was given to the rats which lasted for 10 weeks. Therapeutic effects of SHHZF was compared with that of cyclophosphamide (CTX). High performance liquid-chromatography/electrospray-ionization time of flight mass spectrometer (HPLC/ESI-TOF-MS) combined with pattern recognition approaches including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), was integrated to approximate the comprehensive metabolic signature and discover differentiating metabolites by Agilent MPP 12.1. The changes in metabolic profiling in plasma were restored to their baseline values after SHHZF treatment according to the PLS-DA score plots. Results The results indicated that 23 ions as “differentiating metabolites”. The alterations in those metabolites were associated with perturbations in fatty acid and bile acid metabolism, in response to liver cancer through immune and nervous system. And SHHZF could increase the uptake and utilization of linoleic acid and oleic acid, increase arachidonic acid-like substance content and enhance organism immunity of liver cancer rats. And it also could increase the translation from phosphatidylethanolamine (PE) to phosphatidylcholine (PC), linoleic acid metabolism and inhibits abnormal metabolism of bile acid. Conclusions The mechanism of therapeutic effects of SHHZF on liver cancer by adjusting the activities of PE N-methyl transferase (PEMT), Lysophospholipase D, methylenetetrahydrofolate reductase (MTHFR) and lysophospholipase was elucidated by the method of metabonomics for the first time. [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 Schizonepeta tenuifolia Briq. (ST) herbs have been used as a Traditional Chinese Medicine (TCM) for treating colds for thousands of years. The volatile oil is considered as the main material basis responsible for the efficacy of ST and has attracted lots of attention on its anti-inflammatory effect recently. Aim of study This paper investigated the anti-inflammatory effects of the distilled volatile oils from Schizonepeta tenuifolia (STVO) that were collected at different harvesting times on carrageenin-induced pleurisy in rats. Based on the anti-inflammatory effects, instead of contents of marker components, we aim to evaluate the quality and determine the appropriate harvesting time of ST. Materials and methods There were eleven groups with eight male rats in each randomly. They were model group, control group, positive group (dexamethasone) and eight groups treated with eight STVOs at different harvesting times. All treatments were performed by gavage and administered once a day on four consecutive days. One hour after the last treatments, except the rats in control group, those in other groups were treated with carrageenin to induce the pleurisy. Four hours later, all the rats were sacrificed and their pleurisy exudates and lung tissues were collected for further analysis. To evaluate the comprehensive anti-inflammatory effect of the eight STVOs, multi-attribute comprehensive index method (MACIM) was used to obtain the integration of various effects. Results All the eight STVOs could decrease the seven indicators relating to pleurisy, which were exudate volume, leukocytes, protein level, myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukine-1β (IL-1β). Majority of these decreases were significant (P<0.01, P<0.05). As far as each indicator was concerned, each STVO showed different effect from others. With MACIM, it was found that STVO in Group 6 was the most effective one with the highest V s and appropriate harvesting time of ST was in late September. Conclusions The study may provide scientific basis to further understanding of the mechanism of STVO in anti-inflammatory effect of carrageenin-induced pleurisy. Meanwhile, this study also provides a new access to determining the appropriate harvesting time of TCM and even evaluating the quality of TCM. [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]

Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Roots of Angelica sinensis ( Oliv. ) Diels (AS) a commonly used herbal, always act as an anti-inflammatory drug in Chinese traditional therapy. In clinical use, AS is always processed before being used for the reason that processing can increase its therapeutic effect. Recent studies have shown that volatile oil of AS (VOAS), an important component in AS, has evident anti-inflammatory activities. Aim of the study In this study, our aim is to evaluate the anti-inflammatory effects of volatile oils from processed products of AS. Materials and methods In this paper, volatile oils from stir-fried AS (C-VOAS), parched AS with alcohol (J-VOAS), parched AS with soil (T-VOAS), and parched AS with sesame oil (Y-VOAS) were applied to intervene the carrageenan-induced acute inflammation model rats. GC–MS based metabolomics was utilized to determine different metabolites in the inflammatory exudate and plasma samples. Results The results showed that VOASs could significantly inhibit the release of PGE2, HIS, 5-HT and TNF- α , among which C-VOAS and J-VOAS expressed better effect. Otherwise, 14 potential biomarkers were identified respectively in inflammatory exudate and plasma, which changed highly significantly ( P <0.01) in C-VOAS and J-VOAS groups. Conclusions We inferred that the anti-inflammatory effect of C-VOAS and J-VOAS were superior to other VOASs. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance It is vital for astronauts to develop effective countermeasures to prevent their decline of cognitive performance in microgravity to make space-flight missions successful. The traditional Chinese herbal formula Kai Xin San (KXS) has been used to treat amnesia for thousands years. It is a traditional complex prescription comprising of ginseng (Panax ginseng C. A. Meyer), hoelen (Poria cocos (Schw.) Wolf), polygala (Polygala tenaifolia Willd), and acorus (Acorus tatarinowii Schott). Previous study showed KXS could improve CMS-induced memory impairment in rats. Material and methods In this paper, a unique environmental factor—microgravity (weightlessness) was simulated as hindlimb suspension (HLS) by tail in rats for two weeks as the HLS animal model. The KXS at the doses of 0.3 or 0.6 g/kg p.o. daily was administrated to HLS rats for two weeks at the same time of HLS, the memory behavior tests were investigated with Morris water maze (MWM) and Shuttle Box (SB) test. The levels of ROS, 8-OHdG and 3-nitrotyrosine (3-NT) in the serum, and AChE and ChAT activity in the brain of rats were determined by ELISA or biochemical analysis. Results After HLS for two weeks, the escape latency and the swimming distance were significantly increased in the MWM test in rats in the HLS group, compared with control group. The percent of swimming distance in target quadrant and the number of target crossing was significantly decreased in rats in the HLS group compared with the control group. Performance in the SB test showed, the numbers and the distance of active avoidance was decreased from day 4 to day 7, the time spent in electric area was increased in rats in the HLS group compared with the control group. Administration of KXS 0.3 or 0.6 g/kg to the HLS rats for two weeks significantly reduced the escape latency and the swimming distance, increased the percentage of swimming distance in target quadrant and the number of target crossings (P<0.01, compared with the HLS group) in the MWM test. Similar treatment with KXS increased the numbers and the distance of active avoidance (P<0.01, compared with the HLS group) and reduced the time spent in electric area after training 3 days in the SB test (P<0.01, compared with the HLS group). The HLS induced the increase of the ROS, 8-OHdG and 3-NT in the serum of rats, but has little influence on the AChE, ChAT activity in the brain. Only the AChE activity in the cortex and the ChAT activity in the hippocampus had some changes in rats in the HLS model group. After administration of KXS 0.6 g/kg for two weeks, the abnormal levels of ROS, 8-OHdG, 3-NT were found reversed in the serum of rats (P<0.05, compared with HLS model group). And KXS 0.3 g/kg was found reversed the increased AChE activity in the cortex. Conclusions Experimental results from this study show that KXS may improve memory deficiency induced by HLS, its mechanisms are major related to antioxidant activities, rather than the central cholinergic system. [ABSTRACT FROM AUTHOR]

Hymenocallis littoralis (Jacq.) Salisb. Also known as Pancratium littorale Jacq. And Hymenocallis panamensis Lindl., is a medicinal plant from the family Amarylideceae used for emetic and wound healing and has manifested anti-neoplastic, anti-oxidant, and anti-viral properties. The aim of this paper is to investigate the anti-inflammatory potential and molecular mechanism of H. littoralis against lipopolysaccharide (LPS)-induced macrophages and in vivo HCl/EtOH-induced gastritis mucosal injury models. The production of pro-inflammatory cytokines and mediators was evaluated by Griess assay, RT-PCR, and real-time PCR. Moreover, the relevant proteins of mitogen-activated protein kinases (MAPKs) including ERK, JNK, p38, c-Jun, and c-Fos were detected using immunoblotting. We demonstrated that H. littoralis prominently dampened production of nitric oxide (NO) in LPS-, poly I:C-, or pam3CSK-stimulated RAW264.7 cells; down-regulated the expression levels of interleukin 6 (IL-6) and inducible nitric oxide synthase; and markedly attenuated the luciferase activities of AP-1 reporter promoters. Moreover, H. littoralis administration prominently downregulated c-Fos and c-Jun phosphorylation as well as JNK1, ERK2, and MKK7 overexpression in HEK 293T cells. Furthermore, H. littoralis displayed anti-inflammatory effects in the HCl/EtOH-induced gastritis mice model. Cumulatively, these results demonstrated that H. littoralis exerts eminently anti-inflammatory activities in LPS-stimulated RAW264.7 cells in vitro and in HCl/EtOH-induced gastritis mice models in vivo. These activities could be attributed to its modulatory effects on the MAPK signaling pathway. [Display omitted] • Hymenocallis littoralis ethanol extract (Hl-EE) is able to mediate the inflammatory response. • Hl-EE downregulates the expression levels of iNOS and IL-6 at the transcriptional level. • Hl-EE exerts eminently anti-inflammatory activities through targeting ERK/JNK in the MAPK signaling pathway. • Hl-EE exhibits extremely strong efficacy in HCl/EtOH gastritis model in vivo. [ABSTRACT FROM AUTHOR]

Marsdenia tenacissima (Roxb.) Moon, (M. tenacissima) a traditional herbal medicine, has been used for thousands of years. It is noted in Dian Nan Ben Cao that M. tenacissima is bitter in flavor and cold in property, and extracts possess diverse pharmacological effects, including immunomodulation and anti-tumor activities. The anti-tumor effects of M. tenacissima extracts (MTE) have been repeatedly confirmed, and this medicine has also been extensively applied in cancer treatment or prognostic adjuvant therapy, with significant curative effect. This study aims to comprehensively analyze the anti-tumor mechanism of M. tenacissima starting from the key features of traditional Chinese medicine and by studying the main active components individually to identify anti-tumor targets in the context of hepatocellular carcinoma. Molecular network profiling and multi-omic joint analyses were conducted using an H22 mouse model of hepatocellular carcinoma to determine the main active ingredients in MTE and the underlying anti-tumor mechanisms. Tenacissosides I, H, and G (TI,TH and TG) were found to be the likely active ingredients of MTE in the treatment of hepatocellular carcinoma. These compounds were shown to promote apoptosis, inhibit angiogenesis and improve immune function through targeting P53, JAK-1 and HIF1α, respectively. For the first time, based on the theory that multiple components and multiple targets synergistically exert the beneficial effects of a traditional Chinese medicine, this paper comprehensively analyzes the mechanisms of action of M. tenacissima and provides a novel strategy for the subsequent development of anti-tumor therapies. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Pharmacokinetic studies on traditional Chinese medicine are useful to evaluate and predict the drug efficacy and safety. The renal impairment may affect drug clearance and other pharmacokinetic processes which can increase toxicity and drug to drug interactions or cause ineffective therapy. Pharmacokinetic studies in pathological status rats might be meaningful for revealing the action mechanism and improving clinical medication of the herb medicine. Materials and methods A highly sensitive and rapid ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) method with multiple-reaction monitoring (MRM) mode was developed and validated for simultaneous quantitation of morroniside and loganin in normal and doxorubicin-induced chronic kidney disease (CKD) rat plasma after oral administration of Shanzhuyu (fruit of Cornus officinalis ) extract. Results Both calibration curves gave satisfactory linearity ( r >0.99) at linear range of 1.96–1962.5 ng mL −1 for morroniside, 1.53–1531.25 ng mL −1 for loganin. The precision and accuracy of the in vivo study were assessed by intra-day and inter-day assays. The percentages of relative standard deviation (RSD) were all within 9.58% and the accuracy (RE) was in the −6.02% to 8.11% range. The extraction recoveries of morroniside, loganin and internal standard (IS) were all >67.62% and the matrix effects ranged from 95.07% to 102.75%. Conclusions The pharmacokinetic behavior of morroniside and loganin in normal and CKD rat plasma was determined in this paper. The significant different pharmacokinetic parameters might partly result from the changes of P-glycoprotein and metabolic enzymes in the pathological state. The pharmacokinetic research in the pathological state might provide more useful information to guide the clinical usage of the herb medicine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Frankincense (FRA), Ruxiang, is the resin of Boswellia carterii Birdw and Boswellia bhaw-dajiana Birdw which has been used for centuries as formulas to improve the circulation and to relieve pain against carbuncles. Stir-fried Frankincense (SFF) and vinegar processed Frankincense (VPF) are two major processed Frankincense, and the processing procedures reportedly enhance the curative efficacy or reduce the side effects of FRA. This paper describes the comparisons in plasma pharmacokinetic behaviors of 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA) in FRA and its processed products, and their effects on coagulation factors and blood clotting tetrachoric, using an acute cold blood-stasis animal model after oral administration of FRA, SFF, and VPF. Materials and methods For pharmacokinetic study, Sprague–Dawley (SD) rats were randomly divided into three groups, including group FRA, group SFF and group VPF. And the plasma samples were analyzed by HPLC. For study of anticoagulatory effect, SD rats were randomly divided into six groups, including control, acute cold blood-stasis model, Fu-fang-dan-shen tablet- (0.75 g/kg), FRA-, SFF-, and VPF-treated (2.7 g/kg) groups, respectively. The serum contents of thrombin–antithrombin complex (TAT), D-dimer (D-D), and prostacyclin (PGI 2 ) of each group were measured by ELISA. The values of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were also assessed by hematology analyzer. Results Significantly increased levels of C max , AUC, T 1/2, and MRT were found in rats treated with the processed products. In addition, decreased levels of D-D and TAT and increased contents of PGI 2 were observed in rats given FRA and its processed products, compared with that of the model group. Moreover, VPF improved anticoagulation more than SFF in the animals. Conclusions The observed improvement of anticoagulation by processed FRA may result from the increased absorption and bioavailability of triterpenoids. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Schefflera octophylla (Lour.) Harms, a traditional Chinese herb mainly distributed in Southeast Asia, is extensively prescribed to alleviate pain and treat rheumatoid arthritis (RA), influenza, throat swelling, pain, etc. In this paper, the antinociceptive and anti-inflammatory activities of the ethanol extract and its five different polar fractions of this plant were evaluated. Furthermore, the anti-rheumatoid arthritis activity of the ethanol extract and its active fraction (CHCl 3 fraction) were evaluated. And the chemical constituents of the CHCl 3 active fraction displayed significant antinociceptive and anti-inflammatory activities were investigated. Materials and methods Antinociceptive and anti-inflammatory activities were investigated by hot plate test, acetic acid-induced abdominal writhing test and formalin test, xylene-induced ear edema test. The anti-rheumatoid arthritis activity was evaluated through the model of adjuvant-induced arthritis (AA) in rats, paw swelling, pain response, arthritis index and histopathological changes of ankle, the levels of TNF-α, IL-1β, IL-6 and rheumatoid factor (RF) of rats were detected. The chemical constituents of the CHCl 3 fraction were isolated using chromatographic techniques. Their structures were elucidated by spectroscopic data analysis. Results The results showed that the ethanol extract of S. octophylla has significant dose-dependent anti-inflammatory and antinociceptive activities. And its five different polar fractions especially the CHCl 3 fraction significantly inhibited the abdominal writhing induced by acetic acid and ear edema induced by xylene, also increased pain threshold in hot plate test in 120 min and reduced ticking times in formalin test. The ethanol extract of S. octophylla and the CHCl 3 fraction demonstrated an anti-RA effect in a dose-dependent manner. The levels of TNF-α, IL-1β and IL-6 in ethanol extract (600 mg/kg) and CHCl 3 fraction (300 mg/kg) groups were significantly lower than those of the model group. The chemical constituents study of the CHCl 3 fraction from S. octophylla led to six triterpenoids which were identified as taraxerone ( 1 ), 3-epi-taraxerol ( 2 ), aleuritolic acid ( 3 ), 3-oxofriedelan-28-oic acid ( 4 ), 3β,19α -dihydroxy-urs-12-ene- 24,28-dioic acid ( 5 ) and asiatic acid ( 6 ). Compounds 1 – 5 were obtained from this plant for the first time. Conclusion This study proved the antinociceptive, anti-inflammatory and anti-rheumatoid arthritis activities of S. octophylla. Triterpenoids obtained from its CHCl 3 fraction may be responsible for those activities. These results could support the fact that S. octophylla is used traditionally to cure inflammatory and pain diseases. [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 Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in China and Japan. In this paper, we report the diuretic activities of the petroleum ether fraction, the ethyl acetate fraction, the n-buthanol fraction, and the remaining fraction, of the ethanol extract of Alismatis rhizoma (AR). Materials and methods The single dose of the petroleum ether fraction, the ethyl acetate fraction, the n-buthanol fraction, and the remaining fraction, of the ethanol extract of AR were orally administered to rats. Urinary excretion rate, pH and electrolyte excretion were measured in the urine of saline-loaded rats. Results In this study, the 100 and 400 mg/kg doses of the ethyl acetate fraction and the 12.5, 25 and 50 mg/kg doses of the n-butanol fraction all produced an increase in urine volume excretion, and all produced a remarkable increase in urine electrolyte excretion. Although the 800 mg/kg doses of the ethyl acetate fraction, the 75 and 100 mg/kg doses of the n-butanol fraction and the 12.5, 25 and 50 mg/kg doses of the remaining fraction significantly decreased the urine output in 6 h, the urine Na + and Cl − excretion were markedly decreased with the n-butanol fraction (75 and 100 mg/kg doses) and the remaining fraction (12.5, 25 and 50 mg/kg doses) while the ethyl acetate fraction at 800 mg/kg doses had slight effect on urine electrolyte excretion. The petroleum ether fraction did not show remarkable diuretic activity in comparison with control group. Conclusions Our present study determined that the ethyl acetate fraction and the n-butanol fraction present notable diuretic effects, and we found a dual effect on renal function showed by AR, including promoting diuretic activity and inhibiting diuretic activity. The components with strong polarities in AR may have anti-diuretic activities, which might be an effect of promoting the sodium-chloride co-transporter in the distal tubule. [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]

Our recently published paper demonstrated that ethyl acetate fractions obtained from Cymbopogon citratus (DC.) Stapf (C. citratus) leaves, which are consumed as infusion in folk medicine due to their therapeutic properties, are rich in polyphenols and exhibit promising antioxidant activity by acting through different mechanisms in vitro. However, studies regarding the toxicity of these fractions are necessary to investigate their safe use in future biomedical applications. This study aimed to investigate the toxicity of ethyl acetate (obtained in acidic and basic conditions and after the essential oil removal from the leaves) and chloroform fractions, essential oil, and its pure constituents, citral and geraniol. The toxicity of C. citratus samples was evaluated by using Artemia salina (A. salina) and human blood cells (leukocytes and erythrocytes). The A. salina lethality assay demonstrated that C. citratus fractions were moderately toxic with LC 50 values ranging from 146.12 to 433.15 μg mL−1, whereas the essential oil and isolated compounds were highly toxic with LC 50 lower than 100 μg mL−1. Leukocyte viability decreased after incubation in the presence of the fractions obtained after the essential oil removal from the plant leaves, as well as in the presence of essential oil, citral and geraniol. The same samples increased the osmotic fragility of erythrocytes, and field emission gun scanning electron microscopy (FESEM) analysis revealed significant changes in cell morphology. Interestingly, our results suggest that the previous removal of essential oil from plant leaves facilitated the extraction of cytotoxic compounds from C. citratus. It was demonstrated that C. citratus ethyl acetate and chloroform fractions, essential oil, as well citral and geraniol were considered toxic to A. salina , cytotoxic to human blood cells and showed to induce alterations in the erythrocyte membrane at higher concentrations. These fractions will be further investigated to identify the phytochemicals involved in the observed cytotoxic effects and explored using in vivo models. [Display omitted] • Cymbopogon citratus samples and isolated compounds were toxic for Artemia salina. • Citral, geraniol and essential oil increased osmotic fragility in human erythrocytes. • FESEM analysis showed that some samples changed erythrocytes morphology. • The removal of essential oil from leaves enhanced the extraction of cytotoxic compounds. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Acorus tatarinowii Schott (AT), belong to the family Araceae, is perennial herbaceous plant mainly present in China, Japan and India. The rhizomes of AT have been used as a famous traditional Chinese medicine for the treatment of central nervous system related diseases. Aim of the study A selective, accurate and sensitive method using gas chromatography-mass spectroscopy (GC–MS) for the simultaneous determination and pharmacokinetic study of β -asarone, α -asarone, elemicin and cis -methyl isoeugenol in rat plasma was developed and validated. Materials and methods The GC–MS system was operated under selected ion monitoring (SIM) mode. The samples were prepared by protein precipitation with acetonitrile after being spiked with an internal standard (1-naphthol). The GC separation was achieved on a DB-1701 column (60 m × 0.25 mm ID, and 0.25 µm film thickness). Results The current GC/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. The analyte calibration curves were linear over a wide concentration range and the lowest limit of quantifications (LLOQ) were 5.53 ng/mL ( β -asarone), 6.50 ng/mL ( α -asarone), 3.10 ng/mL (elemicin) and 7.60 ng/mL ( cis -methyl isoeugenol). After oral administration 0.9 g /Kg of AT rhizomes, the maximum plasma concentration (Cmax) was 2508.6±498.7 ng/mL for β-asarone, 257.5±37.1 ng/mL for α -asarone, 345.5±33.4 ng/mL for elemicin and 452.7±59.1 ng/mL for cis-methyl isoeugenol, respectively. The time to reach the maximum plasma concentration ( T max ) was 1.42±0.18 h for β -asarone, 1.58±0.19 h for α -asarone, 1.67±0.24 h for elemicin and 1.75±0.38 h for cis -methyl isoeugenol, respectively. Conclusion This paper described a simple, sensitive and validated GC–MS method for simultaneous determination of four phenylpropanoids in rat plasma after oral administration of the essential oil of AT rhizomes and investigated on their pharmacokinetics studies as well. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Extracts from Ginkgo biloba L. leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components, but some non-flavonoid and non-terpenoid components also exist in this extract. In the study of this paper, an investigation was carried out to compare the pharmacokinetic parameters of fourteen compounds to clarify the influences of non-flavonoid and non-terpenoid fraction (WEF) on the pharmacokinetics profile of the flavonoid fraction (FF) and the terpene lactone fraction (TLF) from Ginkgo biloba extracts. Materials and methods A selective and sensitive UPLC-MS/MS method was established to determine the plasma concentrations of the fourteen compounds to compare the pharmacokinetic parameters after orally administration of FF, TLF, FF-WEF, FF-TLF, TLF-WEF and FF-TLF-WEF with approximately the same dose. At different time points, the concentration of rutin (1), isoquercitrin (2), quercetin 3-O-[4-O-(-β-D-glucosyl)-α-L-rhamnoside] (3), ginkgolide C (4), bilobalide (5), quercitrin (6), ginkgolide B (7), ginkgolide A (8), luteolin (9), quercetin (10), apigenin (11), kaempferol (12), isorhamnetin (13), genkwanin (14) in rat plasma were determined and main pharmacokinetic parameters including T1/2, Tmax, Cmax and AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student's t-test with P<0.05 as the level of significance. Results FF and WEF had no effect on the pharmacokinetic behaviors and parameters of the four terpene lactones, but the pharmacokinetic profiles and parameters of flavonoids changed while co-administered with non-flavonoid components. It was found that Cmax and AUC of six flavonoid aglycones in group FF-WEF, FF-TLF and FF-TLF-WEF had varying degrees of reduction in comparison with group FF, especially in group FF-TLF-WEF. On the contrary, the values of Cmax, Tmax and AUC of four flavonoid glycosides in group FF-TLF-WEF were significantly increased compared with those in group FF. Conclusions These results indicate that non-flavonoid components in Ginkgo biloba extracts could increase the absorption and improve the bioavailability of flavonoid glycosides but decrease the absorption and reduce the bioavailability of flavonoid aglycones. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Jiao-Tai-Wan (JTW), an important herbal formula consists of Rhizoma coptidis and Cortex cinnamomi powder, is a famous prescription which has been used for centuries to treat insomnia in Traditional Chinese Medicine. The purpose of this study is to compare the pharmacokinetic properties of five protoberberine-type alkaloids (i.e. berberine, palmatine, coptisine, epiberberine and jatrorrhizine), the main bioactive constituents in JTW, between normal and insomnic rats. We also investigate the differences between single-dose and multiple-dose pharmacokinetics of five protoberberine-type alkaloids. Materials and methods: The insomnic rat models were induced by intraperitoneal injection of one-dose para-chlorophenylalanine acid (PCPA). Quantification of five protoberberine-type alkaloids in rat plasma was achieved by using a rapid LC–MS/MS method. Plasma samples were collected at different time points to construct pharmacokinetic profiles by plotting drug concentration versus time and estimate pharmacokinetic parameters. An unpaired Student׳s t test was used for comparisons with SPSS 17.0. Results: The five protoberberine-type alkaloids of single-dose normal groups had slow absorption and low bioavailability, as well as a delay of peak time. In the single-dose oral administration, the C max and T max of five ingredients in insomnic rats had significant differences compared with those of normal rats. In the multiple-dose oral administration, the pharmacokinetic parameters of five protoberberine-type alkaloids varied greatly in insomnic rats. In the normal rats, there were significant differences (P<0.05) in the principal pharmacokinetic parameters such as C max and T max between single-dose and multiple-dose oral administration. In the insomnic rats, the five ingredients of multiple-dose groups showed better absorption than the single-dose groups. Particularly, three peaks were observed in multiple-dose model group of plasma–concentration curves. Conclusions: The pharmacokinetic behavior of five protoberberine-type alkaloids was described in this paper. In both normal groups and model groups, the pharmacokinetic behavior of multiple-dose had significant differences comparing with the single-dose; either single-dose or multiple-dose, the pharmacokinetic behavior of insomnic rats had significant differences comparing the normal rats. Multiple dosing may improve the absorption of JTW in insomnic rats, which will increase the bioavailability and bring into active role in therapeutical effect. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in Asia and Europe. In this paper, we report the diuretic activities of the ethanol extract (EE) and the aqueous extract (AE) of A. rhizoma (AR). Materials and methods: The EE and AE were orally administered to rats. The urinary excretion rate and pH, and electrolyte excretion were measured in the urine of saline-loaded rats. Results: The results showed that EE could increase the urine output at 2.5, 5 and 10mg/kg doses but decrease the urine output at 20, 40 and 80mg/kg doses compared with the control group. The 5 and 10mg/kg doses of EE increased the urine electrolyte excretion, but the effects on Na+/K+ values were too weak to reach statistical significance. The Na+ excretion and Cl− excretion were markedly decreased with the 20, 40 and 80mg/kg doses of EE, but the effect on K+ excretion was notably slight. All of the tested doses of AE produced an increase in urinary excretion, but the increase did not reach statistical significance. Conclusions: This study identified that EE but not AE presents a notable diuretic effect, and EE had diuretic and anti-diuretic effects, which appears to be related to the sodium–chloride co-transporter in the renal distal convoluting tubule. This study demonstrated for the first time that the EE of AR has a dual effect on renal function, including promotion of diuretic activity at lower doses and inhibiting diuretic activity at higher doses, and the AR dose should be given more attention in clinical applications. This study will play a critical and guiding role in the dosing of AR as a diuretic drug in clinical applications. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Traditional Chinese medicine (TCM) has been used in clinical practice for several thousand years. TCM has played an indispensable role in the prevention and treatment of disease, especially the complicated and chronic ones. In TCMs, many ingredients which are known to have biological effects just pass through the gut, they do not get into the bloodstream. Study on interactions of these active ingredients with the intestinal bacteria is very helpful to unravel how TCM works. Radix scutellariae was widely used alone or in combination with other medicinal herbs to the treatment of type 2 diabetes mellitus for a long time in China even in Asia. Additionally, the incidence of type 2 diabetes is closely related to the changes of intestinal flora. In this paper, the metabolism of baicalin in Radix scutellariae extract by normal and type 2 diabetic mice intestinal bacteria were firstly investigated. Materials and methods: Ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/QTOF-MS) technique combined with MetabolynxTM software was used for analysis of the metabolic profile of baicalin in Radix scutellariae extracts by the intestinal bacteria from normal and type 2 diabetic mice. Results: The amount of baicalin׳s aglycone (baicalein) in type 2 diabetic mice samples were remarkably more than that in normal mice samples and oroxylin A only existed in type 2 diabetic mice samples. Intestinal bacteria produced not only a small amount of baicalein, but also some conjugates such as hydrogenated baicalin and methylated baicalin. Conclusions: We proposed that β-d-glucuronidases contributed to the deglycosylation prior to absorption. Intestinal bacteria from pathological state mice produced more baicalein, which was well absorbed contributing to the treatment of type 2 diabetes. Additionally, the pharmacological effects of oroxylin A were associated with type 2 diabetes. Hence, the production of metabolites of baicalin might influence the effects of traditional medicines. Thus the study on the metabolism of baicalin by intestinal bacteria from normal and type 2 diabetic mice was of great importance to understanding the effects of traditional medicines. Furthermore, this work demonstrated the potential of the ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry approach with MetaboLynx for quite rapid, simple, reliable and automated identification of metabolites of natural products. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Agastache mexicana subspecies mexicana (Amm) and xolocotziana (Amx) are used in Mexican traditional medicine to relief cultural affiliation syndromes known as “susto” or “espanto”, for “nervous” condition, and as a sleep aid. Despite its intensive use, neuropharmacological studies are scarce, and the chemical composition of the aqueous extracts has not been described. Aims of the study are: (1) To analyze the chemical composition of aqueous extracts from aerial parts of Amm and Amx. (2) To evaluate the anxiolytic-like, sedative, antidepressant-like effects. (3) Analyze the general toxic effects of different doses. Materials and methods: Anxiolytic-like and sedative effects were measured in the avoidance exploratory behavior, burying behavior and the hole-board tests. The antidepressant-like actions were studied in the forced swimming and tail suspension tests. Finally, general activity and motor coordination disturbances were evaluated in the open field, inverted screen and rota-rod tests. The acute toxicity of Amm and Amx was determined by calculating their LD50 (mean lethal dose). The chemical analyses were performed employing chromatographic, photometric and HPLC–ESI-MS techniques. Results: Low doses of Amm and Amx (0.1σ1.0mg/kg) induced anxiolytic-like actions; while higher doses (over 10mg/kg) induced sedation and reduced the locomotor activity, exerting a general inhibition in the central nervous system (CNS). Conclusions: Results support the use of Amm and Amx in traditional medicine as tranquilizers and sleep inducers. Additionally, this paper contributes to the knowledge of the chemical composition of the aqueous extracts of these plants. [Copyright &y& Elsevier]

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: Diuretic plants are widely used in traditional medicine in many countries. However, many of these species have not been subjected to experimental studies to confirm that property. In this paper, a simple new method is proposed to evaluate the diuretic activity of plants. We define a new index that takes into account only the volume of urinary excretion and total ion concentration excreted obtained by specific electrical conductivity measurements. Materials and methods: Urine was collected in a graduate cylinder during the 8h after Artemisia thuscula (AT), Withania aristata (WA), Smilax canariensis (SC) and HCTZ oral administration to laboratory mice. To obtain the new index Diuretic Power (DP), we measured the specific electrical conductivity (?) of the fresh urine samples. We calculated the concentration of a NaCl (or KCl) aqueous solution that has the same specific electrical conductivity as the urine sample. We multiplied this concentration by the corresponding urinary excretion volume, thus obtaining the total mEq. of electrolyte excreted “as if all were NaCl (or KCl)”. Finally, we divided these mEq. by those corresponding to the control to obtain the DP value. Results: HCTZ showed a 40% increase in DP, with respect to the control group, independently of the doses used, and the studied plants produced an increase between 7 and 28%. DP values were compared with other common indexes, DI and SIi, showing that the variation sequence of the three indexes was the same for HCTZ, WA and SC. Conclusions: A new and easy index, that we called diuretic power (DP), for estimating the diuretic activity of drugs or plants is proposed. It allows us to highlight diuretic effect with respect to a control value of a large amount of drugs or plants that had not been previously experimentally studied. [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]