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A new cycloartane sapogenol and a new cycloartane xyloside were isolated from Astragalus karjaginii BORISS along with thirteen known compounds. The structures of the new compounds were established as 3-oxo-6α,16β,24( S ),25-tetrahydroxycycloartane ( 1 ) and 6- O -β- d -xylopyranosyl-3β,6α,16β,24( S ),25-pentahydroxycycloartane ( 2 ) by 1D- and 2D-NMR experiments as well as ESIMS and HRMS analyses. The presence of the keto function at position 3 was reported for the first time for cyclocanthogenol sapogenin of Astragalus genus. In vitro immunomodulatory effects of the new compounds ( 1 and 2 ) along with the n -BuOH and MeOH extracts of A . karjaginii at two different doses (3 and 6 μg) were tested on human whole blood for in vitro cytokine release (IL-2, IL-17A and IFN-γ) and hemolytic activities. The results confirmed that compound 2 , a monodesmosidic saponin, had the strongest effect on the induction of both IL-2 (6 μg, 6345.41 ± 0.12 pg/mL (× 5), P < 0.001) and a slight effect upon IL-17A (3 μg, 5217.85 ± 0.72 pg/mL, P < 0.05) cytokines compared to the other test compounds and positive controls (AST VII: Astragaloside VII; and QS-21: Quillaja saponin 21). All tested extracts and molecules also induced release of IFN-γ remarkably ranging between 5031.95 ± 0.05 pg/mL, P < 0.001 for MeOH extract (6 μg) and 5877.08 ± 0.06 pg/mL, P < 0.001 for compound 1 (6 μg) compared to QS-21 (6 μg, 5924.87 ± 0.1 pg/mL, P < 0.001). Administration of AST VII and other test compounds did not cause any hemolytic activity, whereas QS-21 resulted a noteworthy hemolysis. [ABSTRACT FROM AUTHOR]

Five new limonoids, named sundarbanxylogranins A-E ( 1 – 5 ), were isolated from the seeds of an Indian mangrove, Xylocarpus granatum , collected from mangrove swamps of the Sundarbans, India. The structures of these limonoids were established by HRESIMS and NMR spectroscopic data. Sundarbanxylogranin A ( 1 ) is a rare limonoid containing a bicyclo[5.2.1]dec-3-en-8-one scaffold as the ring A/B-fused core; whereas sundarbanxylogranin B ( 2 ) is a typical mexicanolide with an 8α, 30α-epoxy ring. Sundarbanxylogranins C-E ( 3 – 5 ), among which the former two possess a 29-OMe group with different orientation, belong to a small group of limonoids containing a C 1 - O -C 29 oxygen bridge. Sundarbanxylogranin B exhibited moderate anti-HIV activity with an IC 50 value of 23.14 ± 1.29 μM and a CC 50 value of 78.45 ± 1.69 μM, respectively. [ABSTRACT FROM AUTHOR]

Cranberry procyanidins and quercetin derivatives are considered possible active compounds against urinary tract infections (UTIs). In this paper a small group (n = 6) of healthy subjects consumed a product containing 360 mg of cranberry extract (42.6% w/w of PAC-A and 14.6% w/w of PAC-B) and 200 mg of quercetin. Urine samples were collected after 2,4,6,8, and 24 h. The changes in antiadhesive properties against urophatogenic E . coli of the urinary output were determined in vitro and modification to urinary metabolome were studied by LC-MS. Significant antiadhesive properties of urine samples were observed, with the greatest effect 6–8 h after oral administration, confirming the possible usefulness of cranberry containing products in urinary tract infections (UTI). Metabolomic analysis revealed that valeric acid and valerolactone derivatives that were detected in 6 and 8 h sample, while 4-hydroxy-5-(phenyl)-valeric acid- O -glucuronide and 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone at 6 h and 4-hydroxy-5-(phenyl)-valeric acid- O -sulphate, 3-hydroxyphenyl-valeric acid, 5-(4′-hydroxyphenyl)-gamma-valerolactone-4′- O -glucuronide and 4-hydroxy-5-(3′-hydroxyphenyl)-valeric acid-3′- O -sulphate were the most abundant at 8 h. The present study shows that the antiadhesive properties of urine sample after cranberry consumption are not ascribable to the direct effect of PAC-A, because their levels in urinary output are in the range of ng/mL. On the other hand, significant metabolites that were detected are mainly metabolites of intestinal action on polyphenols and PACs, as well as glucuronidated and sulphated quercetin, suggesting an important role of intestinal modification of phytoconstituents in the cranberry extract mechanism of action. [ABSTRACT FROM AUTHOR]

Daphnauranins A ( 1 ) and B ( 2 ), two sesquiterpenoids were isolated from the roots of Daphne aurantiaca Diels. One is an unprecedented 5/7 oxacycloheptane ring system, the other is a sesquiterpene-lignan complex. Their structures were elucidated by comprehensive spectroscopic methods including MS and NMR. Their absolute configurations were further confirmed by the quantum ECD calculations. Daphnauranins A and B showed anti-insect activities against male fruit fly with anti-feeding rate up to 46.2 ± 7.1 and 44.7 ± 5.4% at 1 mM, respectively. [ABSTRACT FROM AUTHOR]

Older people with frailty are more likely to experience negative psychological well-being, depressive symptoms, anxiety, and stress. Deterioration of psychological outcomes, in turn, further aggravates the frailty status among this vulnerable population. Considering the undesirable effects of polypharmacy on older people, the use of non-pharmacological intervention has attracted increasing attention. However, the effects of non-pharmacological interventions on psychological outcomes are not clear. This review aims to systematically identify and synthesise evidence to examine the effectiveness of non-pharmacological interventions on psychological outcomes among older people with frailty. Eight electronic databases, including PubMed, MEDLINE, EMBASE, CINAHL, APA PsycInfo, Cochrane Library, CNKI and WANFANG were searched from inception to 14 November 2022. Randomised controlled trials and clinical controlled trials of non-pharmacological interventions on psychological outcomes in older people with frailty were included. The quality of the included studies was assessed using The Cochrane Risk of Bias Tool v2. Meta-analysis was performed using the RevMan5.3. The certainty of the evidence was evaluated by GRADE approach. A total of 4726 articles were initially identified and screened for title and abstract. Eventually, 13 articles from 11 studies were included in this review. The results of the overall risk of bias indicated that four studies had low risk; five studies had some concerns, and two studies had high risk. Four types of intervention were identified, including physical exercise (n = 3), complementary and alternative medicine (music therapy = 1, acupressure = 1), case management (n = 5), and advance care planning (n = 1). The pooled analysis showed that group-based physical exercise had significant beneficial effects on depressive symptoms (SMD: − 0.46, 95% CI: − 0.81 to − 0.10, p =.01; low certainty). There is no difference between the effects of case management and usual care on depressive symptoms (SMD: 0.02, 95% CI: − 0.14 to 0.19, p =.79; high certainty). Narrative synthesis of evidence suggested the effects of complementary and alternative medicine on improving depressive symptoms and general mental status. Psychological outcomes in older people with frailty are understudied. Group-based physical exercise could be a strategy to reduce depressive symptoms among older people with frailty. There is limited evidence showing the effects of complementary and alternative medicine on improving psychological outcomes. More rigorous trials are needed to examine the effects of non-pharmacological interventions on psychological outcomes among older people with frailty. (PROSPERO): CRD42022303370. [ABSTRACT FROM AUTHOR]

Aconitum karacolicum from northern Kyrgyzstan (Alatau area) contains about 0.8–1% aconitine as well as other aconite derivatives that have already been identified. In this paper, we compare several methods for the further purification of an Aconitum karacolicum extract initially containing 80% of aconitine. Reverse-phase flash chromatography, reverse-phase semi-preparative HPLC, centrifugal partition chromatography (CPC) and recrystallization techniques were evaluated regarding first their efficiency to get the highest purity of aconitine (over 96%) and secondly their applicability in a semi-industrial scale purification process (in our case, 150 g of plant extract). Even if the CPC technique shows the highest purification yield (63%), the recrystallization remains the method of choice to purify a large amount of aconitine as i) it can be easily carried out in safe conditions; ii) an aprotic solvent is used, avoiding aconitine degradation. Moreover, this study led us to the identification of lappaconitine in Aconitum karacolicum , a well-known alkaloid never found in this Aconitum species. [ABSTRACT FROM AUTHOR]

Three propolis samples were collected from different regions of Ecuador (Quito, Guayaquil and Cotacachi) and their methanolic extracts were prepared. Preliminary information supplied by TLC and NMR data, allowed us to define two main types of propolis: Cotacachi propoli sample (CPS), rich in flavonoids and Quito and Guayaquil samples (QPS and GPS) containing triterpenic alcohols and acetyl triterpenes as the main constituents. Two different approaches based on RP-HPLC preparative procedure and NMR structural determination (CPS) and GC–MS analysis (QPS and GPS) were successfully used for the chemical characterization of their major compounds. All three propolis extracts were able to inhibit Leishmania amazonensis growth but propolis sample rich in flavonoids was the most active (IC 50 = 17.1 ± 1.7 μg/mL). In the literature this is the first study on propolis from Ecuador. [ABSTRACT FROM AUTHOR]

A set of PEGylated derivatives of oleanolic and maslinic acids has been semi-synthesised, attaching ethylene glycol, diethylene glycol, triethylene glycol or tetraethylene glycol to the C-28 carboxyl group of these natural triterpenes and some derivatives. Another set of PEGylated derivatives has been semi-synthesised by connecting the same four ethylene glycols to the hydroxyl groups of the A ring of these triterpenic acids, through a carbonate linker, by reaction with trichloromethyl chloroformate. The aqueous solubility of some of these PEGylated derivatives has been compared with that of maslinic acid. The cytotoxic effects of 28 triterpenic PEGylated derivatives in three cancer-cell lines (B16-F10, HT29, and Hep G2) have been assayed. The best results have been achieved with the HT29 cell line, and specifically with the oleanolic acid derivatives having ethylene glycol or tetraethylene glycol attached to the C-28 carboxyl group, which are approximately 27-fold more effective than their natural precursor. Eight PEGylated derivatives have been selected to compare the cytotoxicity results in the HT29 cancer-cell line with those of a non-tumour cell line of the same tissue (IEC-18), four of which were less cytotoxic in the non-tumour cell line. These compounds showed apoptotic effects on treated cells, with percentages of total apoptosis between 20% and 53%, relative to control, at 72 h and IC 50 concentration, and between 29% to 62%, relative to control, for the same time and IC 80 concentration. We have also found that with the treatment of these compounds in HT29 cancer cells, cell-cycle arrest occurred in the G0/G1 phase. Finally, we have also studied changes in mitochondrial membrane potential during apoptosis of HT29 cancer cells, and the results suggest an activation of the extrinsic apoptotic pathway for these compounds. [ABSTRACT FROM AUTHOR]

Three new 2-phenylnaphthalene derivatives, cherrevenaphthalenes A–C ( 1–3 ), and a new polyoxygenated cyclohexene derivative, (−)-uvaribonol F ( 4 ) together with six known compounds, 5–10 , were isolated from the stem and root extracts of Uvaria cherrevensis (Annonaceae). The structures of all isolated compounds were elucidated by spectroscopic analysis. The structures of 3 and 4 were further confirmed by single crystal X-ray diffraction methods. Compound 2 exhibited modest antiplasmodial activity against the P. falciparum stains TM4/8.2 and K1CB1 with IC 50 values of 18.8 ± 3.63 and 23.4 ± 4.08 μM, respectively, and weak cytotoxicity to a Vero cell line. Furthermore, compound 4 displayed cytotoxic activity against a KB cell line with an IC 50 value of 22.1 ± 0.42 μM but was non-cytotoxic to the Vero cell line. Compound 5 revealed stronger cytotoxicity towards the KB cell line, with an IC 50 value of 5.05 ± 0.86 μM and was nearly equally cytotoxic to the Vero cell line. [ABSTRACT FROM AUTHOR]

Four new bi-phenylethylchromones ( 1 – 4 ) were isolated from the EtOAc extract of artificial agarwood induced by holing method originating from Aquilaria sinensis (Lour.) Gilg. The structures of new compounds were unambiguously elucidated by one- and two-dimensional NMR and HRESIMS measurements, and the absolute configuration was determined by analysis of circular dichroism (CD) spectra. All compounds were tested for acetylcholinesterase (AChE) inhibitory activity using modified Ellman's colorimetric method and α -glucosidase inhibitory activity using PNPG method. Compounds 2 – 4 exhibited different levels of inhibitory activity against AChE with the inhibition ratios in the range of 10–45%. However, none of the compounds was active against the α -glucosidase. [ABSTRACT FROM AUTHOR]

Bakuchicin is a furanocoumarin isolated from the seeds of Psoralea corylifolia , which is used in oriental medicine. However, limited information on the pharmacokinetics of bakuchicin is available and in addition, no determined method has been devised to quantify bakuchicin levels in the plasma. In the present study, we developed and validated a quantification method using liquid chromatography (LC) coupled with tandem mass spectrometry (LC-MS/MS), which was applied to a pharmacokinetic investigation in mouse plasma. LC was performed using an ACE 5 C18 column, and a mixture of acetonitrile and water containing 0.1% formic acid was used as the mobile phase at a flow rate of 220 μL/min. Bakuchicin transition ions in multiple reaction-monitoring modes using positive ionization were observed at m / z 187.0 to m / z 131.0. Bakuchicin and the internal standard (reserpine) had retention times of 4.5 and 4.3 min, respectively. Acceptable linearity (r 2 = 0.996) was observed over the concentration range of 20–1000 ng/mL, with a lower quantification limit of 20 ng/mL in mouse plasma. This method was successfully applied to determine the pharmacokinetic parameters of bakuchicin in mouse plasma and showed that the bioavailability of bakuchicin was 58.3% at 5 mg/kg oral administration. [ABSTRACT FROM AUTHOR]

A series of novel β -elemene isopropanolamine derivatives were synthesized and evaluated for their antitumor activity. The results indicated that all of the compounds showed stronger antiproliferative activities than β -elemene as well as improved aqueous solubility. In particular dimer 6q showed the strongest cytotoxicity against four tumor cell lines (SGC-7901, HeLa, U87 and A549) with IC 50 values ranging from 4.37 to 10.20 μM. Moreover, combination of 6q with cisplatin exhibited a synergistic effect on these cell lines with IC 50 values ranging from 1.21 to 2.94 μM, and reversed the resistance of A549/DPP cells with an IC 50 value of 2.52 μM. The mechanism study revealed that 6q caused cell cycle arrest at the G2 phase and induced apoptosis of SGC-7901 cells through a mitochondrial-dependent apoptotic pathway. Further in vivo study in H22 liver cancer xenograft mouse model validated the antitumor activity of 6q with a tumor inhibitory ratio (TIR) of 60.3%, which was higher than that of β -elemene (TIR, 49.1%) at a dose of 60 mg/kg. Altogether, the potent antitumor activity of 6q in vitro and in vivo warranted further preclinical investigation for potential anticancer chemotherapy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Suqingwan (SQW), a traditional Chinese medicine used for treating ulcerative colitis (UC), is composed of 13 kinds of Traditional Chinese medicines (TCMs). According to TCM theory, we investigated whether a simplified prescription composed of the herbs with some functions, would have similar effects to SQW and examined its potential treatment mechanism of action. Materials and methods We categorized the herbs in SQW into four groups according to their traditional functions and used an orthogonal experimental design to obtain nine separated prescriptions (SPs) of SQW. A dextran sulfate sodium (DSS)-induced UC mouse model was used to evaluate the anti-ulcer colitis effects of the nine SPs and the calculated prescription (CP) was obtained based on the orthogonal t values of the disease activity index (DAI) of the nine SPs. The effect of the CP and SP8 were verified in the DSS-induced UC model, and the DAI and histopathology of the UC mice were examined. Myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)−1β, IL-6, IL-4 and IL-10 of the mice in SP8 were investigated to explore the mechanism of action of the optimized prescription with regard to anti-inflammatory and anti-oxidation effects. Results Among the 9 SPs, separate prescription 6, 7 and 8 (SP6, SP7 and SP8) and the SQW formulation all significantly reduced the DAI of the UC mice and, in particular, SP8 had an effect similar to SQW, which consists of Sanguisorba officinalis L., Rehmannia glutinosa Libosch. and four other herbal medicines. In a further investigation, SP8 was found to improve the ulcerative colitis in mice in terms of both clinical symptoms and histopathology. The mortality of mice in the SP8 group was 33.3%, better than CP based on the orthogonal t values (83.3%). SP8 could also reduce the levels of TNF-α, IL-1β, IL-6, MPO and MDA and increase the levels of IL-4 and IL-10 in colon tissue of UC mice in comparison with those of the model group ( p <0.05). Conclusions An optimized prescription (SP8) from SQW was obtained based on an orthogonal experimental design, which involved 6 herbal medicines, with significantly fewer herbs than in the original prescription. SP8 displayed a similar anti-ulcerative colitis activity to SQW, and its in vivo mechanism of action is related to up-regulation of anti-inflammatory cytokines and down-regulation of pro-inflammatory and oxidative factors. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species ( Centrosema pubescens , Moringa oleifera , Tridax procumbens , Polyalthia longifolia , Newbouldia laevis, Eucalyptus maculate , Jathropha tanjorensis ), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. Aim of the study To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. Material and methods Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC 50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. Results Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata , in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei . The EC 50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38 µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC 50 of 1.58 µg/mL. None of the isolated compounds displayed toxicity towards Human Embryonic Kidney cells at concentrations up to 400 µg/mL. In addition, the isolated compounds were active against Leishmania mexicana , as well as against T. congolense . Conclusion We have isolated a clerodane compound from Polyalthia longifolia that shows low toxicity, no cross-resistance with current treatments, and promising activity against both human-infective and veterinary Trypanosoma species. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance There is a decided lack of in-depth studies to evaluate the effectiveness of Chinese Herbal Medicine (CHM) as an adjuvant therapy on the incidence of chronic hepatitis in patients with colon cancer. Aim of the study The aim of this study is to assess whether CHM treatment decreased the incidence of chronic hepatitis in colon cancer patients who received conventional Western medical treatment. Materials and methods A Taiwanese nationwide population-based study of colon cancer patients receiving Western medicine treatment in conjunction with CHM treatment, using data provided by the National Health Insurance (NHI) Research Database, was conducted. A total of 61676 patients were diagnosed with colon cancer in Taiwan within the defined study period, from 1997 to 2010. After randomly equal matching for age, sex, excluding patients younger than 18 years of age, chronic hepatitis before colon cancer diagnosis date, receiving acupuncture and/or moxibustion and taking CHM for less than 30 days, data from 155 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence of CHM and the therapeutic potential of herbal products in treating patients with colon cancer. Results CHM used for patients with colon cancer exhibited significantly decreased incidence rates of chronic hepatitis [hazard ratio (HR)=0.53; 95% confidence interval (CI):0.38–0.74], with multivariate adjustment, compared to those without CHM use. The protective effect of CHM treatment with statistical significance across the stratification of age, gender, co-morbidity and treatment modality was noted. The cumulative incidence of chronic hepatitis was also reduced in patients with colon cancer receiving CHM treatment during a five-year period. In this study, we provide the ten most used single herbs and herbal formulas that were prescribed for patients with colon cancer; moreover, we identify the eight single herbs and five formulas used in CHM treatment which significantly decreased incidence of chronic hepatitis among colon cancer patients. Conclusions This nationwide retrospective cohort study determined that therapy using CHM as an adjuvant modality may have a significant impact on liver protection in patients with colon cancer. [ABSTRACT FROM AUTHOR]

Ethnopharmacological importance The hemiparasitic species Psittacanthus plagiophyllus Eichl. (Loranthaceae), also known as erva de passarinho , is used in folk medicine in the Santarém region in the state of Pará, Brazil, to treat gastritis and a variety of inflammatory disorders. In view of the lack of pharmacological studies on this species in the literature and the fact that it is used constantly by the local population, this study sought to standardize the extract of the leaves of P. plagiophyllus (AEPp) and to assess its anti-inflammatory potential in in vivo tests. Material and methods Quality control and standardization of AEPp were performed following the 5th edition of the Brazilian Pharmacopeia. To assess the in vivo anti-inflammatory activity of AEPp, the carrageenan-induced and dextran-induced rat paw edema models were initially used. To investigate the effect of AEPp on carrageenan-induced leukocyte recruitment and exudate production, the air pouch inflammation model was used. In addition, the antioxidant activity of AEPp was assessed in vitro by the DPPH radical scavenging method. Results The chromatographic profile of AEPp indicated the presence of flavonoids, coumarins and hydrolyzable and condensed tannins. Measurement of phenolics revealed the following percentages in the extract: 12.62±0.18% total phenolics, 5.39±0.01% total tannins, 12.54±0.24% hydrolyzable tannins, 8.37±0.32% condensed tannins and 1.23±0.02% total flavonoids. In 500 and 1000 mg/kg doses (p.o.) AEPp had significant edema-inhibiting activity ( p <0.01) in both the models used, suggesting that the extract may act in vascular and cell events in the inflammatory response and exert an inhibitory effect on mediators responsible for edema. In all the doses tested [250, 500 and 1000 mg/kg (p.o.)], AEPp inhibited total leukocyte and neutrophil migration and reduced the amount of exudate in the air pouch in a dose-dependent manner. Both effects were statistically significant ( p <0.01). The extract also reduced the DPPH radical (maximum reduction 93.13±1.71% at a concentration of 75 µg/mL), indicating that it has antioxidant activity. AEPp, therefore, exhibited considerable in vivo anti-inflammatory activity and in vitro antioxidant activity. This may be due to its high phenolics content. Conclusion These findings provide evidence to support the use of P. plagiophyllus in folk medicine to treat inflammatory disorders. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Herbal medicines have been used for centuries for the management and treatment of various ailments due to the belief that they pose only little or no health risk and side effects, and also, in part, due to their availability, affordability and/or self-supply. However, the increasing information over the recent years on the occurrence of pyrrolizidine alkaloids (PAs) in honey, herbal food and tea products has raised concerns about the safety of herbal medicines with respect to contamination. To this day, little is known on the occurrence of toxic PAs in herbal medicines, especially in tropical West Africa. The aim of this study was therefore to determine the PA content of 70 well-known and widely patronized plant-derived medicinal preparations, which are commercialized in Ghana and some West African countries, in order to ascertain their potential health risk. Materials and methods PAs of the herbal medicinal products, sourced from specialized drugstores and mostly regulatory approved, were analyzed for their PA content by a HPLC-ESI-MS/MS sum parameter method. Results The results show that a total of 60% of the analyzed herbal products were PA positive, indicating an average PA-concentration of 25.0 μg/kg. The maximum PA level (1290.0 μg/kg) was attributed to a regulatory-approved herbal medicine not known, according to the list of declared ingredients, to contain PA-plant parts. Interestingly, higher PA content (average, 30.2 μg/kg) was detected in regulatory-approved herbal medicines, in contrast to lower amount (average, 8.0 μg/kg) detected in non-regulatory-approved products. Conclusion The findings of this study clearly demonstrate that herbal medicines containing PA plants as ingredients, as well as some of those containing plant species not known to produce PAs, are likely to contain hepatotoxic PA at levels higher than the daily dose in food and herbal medicinal products proposed by the European Medicines Agency (i.e. 0.35 μg PA per day for 50 kg adult and 0.14 μg PA per day for 20 kg children). Hence, regulatory authorities are advised to carry out more rigorous quality control tests with respect to PAs so as to minimize the exposure of the consumers to these toxic compounds. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Transmission of traditional knowledge over time and across culturally and historically related territories is an important topic in ethnopharmacology. Here, we contribute to this knowledge by analysing data on medicinal uses in two neighbouring areas of the Western Mediterranean in relation to a historical text that has been scarcely mentioned in historical studies despite its interest. Aim of the study This paper discusses the sharing of popular knowledge on the medicinal uses of plants between eastern Morocco and eastern Andalusia (Spain), focusing on one of the most useful plant families in the Mediterranean area: Lamiaceae. Moreover, we used the classical work of Ibn al-Baytar (13th century CE) The Compendium of Simple Medicaments and Foods as a basis to contrast the possible link of this information, analysing the influence of this historical text on current popular tradition of medicinal plant use in both territories. Materials and methods For data collection, we performed ethnobotanical field research in the eastern part of Morocco, recording current medicinal uses for the Lamiaceae. In addition, we systematically reviewed the ethnobotanical literature from eastern Andalusia, developing a database. We investigated the possible historical link of the shared uses and included in this database the information from Ibn al-Baytar's Compendium . To compare the similarity and diversity of the data, we used Jaccard's similarity index. Results Our field work provided ethnobotanical information for 14 Lamiaceae species with 95 medicinal uses, serving to treat 13 different pathological groups. Of the total uses recorded in Morocco, 30.5% were shared by eastern Andalusia and found in Ibn al-Baytar's work. There was a higher similarity when comparing current uses of the geographically close territories of eastern Morocco and eastern Andalucía (64%) than for eastern Morocco and this historical text (43%). On the other hand, coincidences between current uses in eastern Andalusia and the ones related in the Compendium are lower, 28%. Conclusions The coincidence of the current ethnobotanical knowledge in the two territories is high for the Lamiaceae. Probably the shared historical background, recent exchanges, information flow, and the influence of the historical herbal texts have influenced this coincidence. In this sense, there is a high plant-use overlap between Ibn al-Baytar's text and both territories: nearly half of the uses currently shared by eastern Morocco and eastern Andalusia were included in the Compendium and are related to this period of Islamic medicine, indicating a high level of preservation in the knowledge of plant usage. The study of 14 species of Lamiaceae suggests that this classical codex, which includes a high number of medicinal plants and uses, constitutes a valuable bibliographical source for comparing ancient and modern applications of plants. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Liver disorders are a major health problem in Cambodia, where some patients prefer to seek treatment from traditional healers. The aim of the study was to document the knowledge and practices of these healers in four Southern Cambodian provinces. Materials and methods An ethnopharmacological survey was carried out from September 2015 to January 2016 in Cambodian urban and rural areas. Thirty-three Khmer traditional healers (KTH) were interviewed using a semi-structured questionnaire including socio-demographic data, healer's formation and their professional practice conditions, perception of liver diseases (types and causes of liver disorders, diagnostic methods and symptoms of liver problems), dietary recommendations given to patients, and herbal remedies used to treat them. For each medicinal plant mentioned in herbal remedies, the local name, part of the plant, mode of preparation and administration, and their properties, according to the healers, were recorded. The plants mentioned by the traditional therapists were collected and later identified by specialists. Results Different types of liver disease are identified by the healers, and diagnosis was mostly based on reading medical records, and by observing the yellow discoloration of the skin and eyes. A total of 42 herbal remedies including 83 medicinal plants belonging to 40 families were mentioned for treating liver disorders. The most predominant families were Leguminosae and Poaceae. Among the plants reported, Cananga latifolia , Andrographis paniculata , Smilax aff. glabra , Gomphrena celosioides, Passiflora foetida and Physalis minima were the most cited species. A large part of the herbal remedies used were multi-ingredient recipes, and were prepared mainly by a decoction administered orally. Plants are combined in multi-ingredient recipes, and selected on the basis of their properties ( trocheak , psah , somrap mé rok , ktchol ) which originate from Khmer medical concepts. Most of the plants used by healers have a wide ethnobotanical use for liver disorders, and have been studied for their hepatoprotective activity and related activities on the liver. Conclusion In the diagnosis and treatment of liver diseases, KTH have incorporated biomedical concepts and new practices, which suggest that they could be defined as neotraditional healers. Medicinal plants constitute the core of traditional medicine practice by these healers, and these plants play a very important role in the health care of people with liver problems in Cambodia. Therefore, more attention should be paid to the integration of healers in national health care programs for the development of combined therapies. Furthermore, two plant species (i.e. Cananga latifolia and Willughbeia edulis ) were found to be widely used for treating liver disorders in our survey, and should be studied for their pharmacological potential for liver problems. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Rhizoma Smilacis Glabrae (RSG) is traditionally used to treat gynecological disease, which is simply recorded in Chinese Pharmacopoeia. However, whether it has effect on upper genital tract inflammation (UGTI) is unclear. Aim of the study To evaluate the pharmacological effect of RSG on UGTI in rats and analyze its phytochemistry characteristics. Materials and methods The substances in RSG extract was qualified by LC-Q-TOF-MS method, and 11 substances were further quantified. The RSG extract, at dose of 241, 482 (clinical dose) and 964 mg/kg/day, was orally administered to UGTI rats whose upper genital tracts were multi-infected with pathogens. Infiltrations of neutrophil and lymphocyte and productions of IL-1β, IL-6, CXCL-1, MCP-1, RANTES, PGE2, COX-2, NF-κB p65 and IκB-α in upper genital tract were examined to evaluate the effects of RSG and its potential mechanism. Results A total of 77 substances were detected in RSG extract, with 50 substances putatively identified, most of which were flavonoids, phenolic acids and phenylpropanoids. The quantification analysis showed flavonoid had a relative high amount. In pharmacological study, RSG extract suppressed infiltrations of inflammatory cells, reduced over-productions of factors involved in inflammation and pelvic pain. A potential mechanism of these effects was blocking NF-κB signal pathway. Conclusions The RSG extract exhibited anti-inflammatory effect on UGTI, with a potential mechanism of blocking the activation of NF-κB signal pathway. The effect may be involved in the presence of substances, such as flavonoids and phenolic acids. [ABSTRACT FROM AUTHOR]

Ethnophamacological relevance Pogostemon cablin is a medicinal herb widely used to treat gastrointestinal diseases in many Asian countries. Pogostone is an important constituent of Pogostemon cablin , and possesses various bioactivitys. In this study, we performed to investigate the anti-colorectal tumor property of Pogostone by inducing aurophagy and apoptosis in human colorectal cancer cells, and to define the potential molecular mechanisms. Materials and methods In vitro, The anti-tumor activity of pogostone was assessed using MTT assay. Autophagy was monitored by transmission electron microscopy observation and mRFP-GFP-LC3 fluorescence analysis in colorectal tumor cell line. Apoptosis was measured by flow cytometry and annexinV-FITC/PI staining. The protein expressions or activition of LC3-Ⅱ, AKT, mTOR, caspase-3 and caspase-7 were detected through western blotting. In vivo, the anti-tumor effect of pogostone was tested with HCT116 colorectal tumor cells transplantation tumor model. The expression of Ki-67 was determined by Immunohistochemistry staining and the apoptosis was evaluated using TUNEL assay. Results In vitro, pogostone exhibits significant anti-tumor activity against human cancer cell lines, especially for HCT116 (18.7±1.93 μg/ml). Transmission electron microscopy observation, mRFP-GFP-LC3 fluorescence analysis, flow cytometry and assay and western blotting detection revealed that the anti-colorectal tumor activity of pogostone was dependent on inducing autophagy and apoptosis through up-regulating the expression of LC3-Ⅱ, cleaved caspase-7 and caspase-3, and decreasing the phosphorylation of AKT/mTOR. In vivo , 150 mg/kg pogostone inhibited the HCT116 tumor growth in immunodeficient mice with an inhibitory rate of 43.3%, decreased the expression of Ki67, and induced apoptosis in three days. Conclusion Pogostone showed anti-colorectal tumor effects by inducing autophagy and apoptosis involving PI3K/Akt/mTOR axis. Thus, pogostone may be a promising lead compound to be further developed for cancer therapy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Terminalia bellerica Roxb. fruits are rich in a variety of biologically active ingredients. Tharu and Buksa tribes of Udham Singh Nagar, Uttarakhand, India use grilled fruits of Terminalia bellerica as an effective cure for diarrhea Aim of the study We validated the ethnobotanical claim by comparing the antidiarrheal effect of grilled fruits (GF) with dried fruits (DF). Materials and methods The 50% ethanolic extracts of GF and DF were successively fractionated; the antioxidant and bacterial inhibition activity were studied using DPPH free radical scavenging, anti-lipid peroxidation and broth dilution method respectively. Difference in metabolites of ethyl acetate fractions of GF and DF was analyzed using GC-MS, gallic acid content was determined through HPTLC. Further the in-vivo antidiarrheal effect of ethyl acetate fractions of DF and GF was studied on castor oil induced diarrhea model. Results The ethyl acetate fractions showed potential DPPH free radical scavenging (IC 50 11.13 µg/ml in DF and 8.56 µg/ml in GF), anti-lipid peroxidation and antibacterial activity. The non-targeted metabolic profiling showed higher content of tartaric acid, valeric acid, gallic acid, succinic acid, oxalic acid, malonic acid, malic acid, 1,2,3 trisbenzene, uridine and 11-eicosenoic acid in GF. The HPTLC results indicated that gallic acid content was 2.8 (±0.14) and 4.92 (±0.28) mg/g while ellagic acid content was 4.7 (±0.32) and 4.45 (±0.45) mg/g dry powder in DF and GF respectively. According to i n vivo antidiarrheal activity DF and GF (100 mg/kg oral) inhibited diarrhea by 41.87% and 71.72% respectively. Conclusion Grilling significantly altered the levels of metabolites in T. bellerica fruits which could be responsible for its increased therapeutic potential. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The stem bark of Dilodendron bipinnatum Radlk. (Sapindaceae), a tree native to Pantanal of Mato Grosso, Brazil, popularly known as “mulher-pobre” (poor woman), has been historically used by the locals, after decoction and maceration, for the treatment of inflammatory conditions. We have recently shown that these preparations indeed possess anti-inflammatory properties, which are mediated by the inhibition of cell migration and the modulation of Th1 and Th2 cytokines. The NO pathway was not affected. Aim of the present study The aim of the present study was to further investigate the mechanisms responsible for the anti-inflammatory properties of the hydroethanolic extract of the stem bark of Dilodendron bipinnatum (HE Db ). Materials and methods HEDb was obtained by maceration of the stem bark of D. bipinnatum as previously described. The corresponding effects on a macrophage-like cell line, RAW 264.7, were investigated. The apoptosis of RAW 264.7 upon treatment with LPS, HEDb and N-acetyl- L -cysteine (NAC) was assessed by flow cytometry, using an Annexin V-PE kit. The production of inflammatory cytokines (TNF-α, IL-1β and IL-10) and PGE 2 were evaluated by ELISA, after cell challenge with LPS. The intracellular redox state and changes in mitochondrial membrane potential were also assessed by flow cytometry, using DCFH-DA and JC-1 as probes. The protein expression levels of MAPK p-p38, p-ERK, p-JNK, MKP-1 and COX-2 were analysed by western blotting. Nuclear translocation of NF-қB was assessed by immunofluorescence microscopy. The quantified results are presented as a nuclear:cytoplasmic ratio. Results LPS, HEDb and NAC did not appear to decrease the number of viable cells in comparison to control treatment. HEDb attenuated the production of pro-inflammatory cytokines (IL-1β and TNF-α) and PGE 2 induced by LPS but did not affect IL-10. The production of ROS was also inhibited by HEDb (1, 5 or 20 µg/mL), even at the lowest concentration; at 20 µg/mL, HEDb was more effective than NAC, which was used as a positive control (74.1% and 66.2% inhibition of LPS's effect, respectively). LPS induced an increase in ΔΨm (19.2%, p<0.001), while HEDb inhibited the change in ΔΨm (7.7% at 20 µg/mL, p<0.001). The results of western blotting showed that HEDb inhibited the expression of MAPK p-p38, p-JNK and COX-2, while the expression of MKP-1 was increased. p-ERK was not affected. LPS promoted the nuclear translocation of NF-қB p65 (67%, p<0.01) in RAW 264.7 cells, in comparison to baseline (33%). Pre-treatment with HEDb inhibited this translocation of NF-κB p65 (58% at 20 µg/mL, p<0.001). Conclusion: HEDb has a potent anti-inflammatory activity and acts on multiple targets and biological pathways of potential therapeutic relevance. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Psidium guajava and Tagetes erecta have been used traditionally to treat gastrointestinal parasites, but their active metabolites and mechanisms of action remain largely unknown. Aim of the study To evaluate the anthelmintic potential of Psidium guajava and Tagetes erecta extracts on Levamisole-sensitive and Levamisole-resistant strains of the model nematode Caenorhabditis elegans. Materials and methods Aqueous extracts of Psidium guajava (PGE) and Tagetes erecta (TEE) were assayed on locomotion and egg-laying behaviors of the wild-type (N2) and Levamisole-resistant (CB193) strains of Caenorhabditis elegans . Results Both extracts paralyzed wild-type and Levamisole-resistant nematodes in a dose-dependent manner. In wild-type worms, TEE 25 mg/mL induced a 75% paralysis after 8 h of treatment and PGE 25 mg/mL induced a 100% paralysis after 4 h of treatment. PGE exerted a similar paralyzing effect on N2 wild-type and CB193 Levamisole-resistant worms, while TEE only partially paralyzed CB193 worms. TEE 25 mg/mL decreased N2 egg-laying by 65% with respect to the untreated control, while PGE did it by 40%. Conclusions Psidium guajava leaves and Tagetes erecta flower-heads possess hydrosoluble compounds that block the motility of Caenorhabditis elegans by a mechanism different to that of the anthelmintic drug Levamisole. Effects are also observable on oviposition, which was diminished in the wild-type worms. The strong anthelmintic effects in crude extracts of these plants warrants future work to identify their active compounds and to elucidate their molecular mechanisms of action. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Campomanesia velutina leaves and branches infusions are used in Brazilian folk medicine to treat diarrhea and to ameliorate intestinal cramps, respectively. Aim of the study Carry out the acute and sub chronic pre-clinical evaluation and thus assess the safety and toxicological potential of the specie. Materials and methods In vivo toxicity was evaluated by acute and sub chronic toxicity assays conducted according to the guidelines of the Brazilian Agency of National Health Surveillance (Agência Nacional de Vigilância Sanitária – ANVISA). For acute toxicity evaluation, a single dose of aqueous extracts from the leaves (AEL) and branches (AEB) of Campomanesia velutina were orally administered to mice at doses of 300, 600 and 1200 mg/kg. Then, the animals were observed for 14 days. In the sub chronic study, the extracts were orally administered to mice for 14 days at doses of 300, 600 and 1200 mg/kg. To assess the toxicological effects, animals were closely observed on general behavior, clinical signs of toxicity, body weight, food and water intake. At the end of the experiment, it was performed biochemical and hematological evaluations, as well as histopathological analysis from the following organs: brain, heart, lungs, liver, stomach, small intestine (section) and left kidney. Preliminary phytochemical analysis was performed using thin layer chromatography (TLC) and colorimetric pharmacognostic tests. Results In oral acute assay, treatment with AEB at the major dose (1200 mg/kg) caused diarrhea, abdominal cramps and tremors in females. These effects were reversed at 4th hour. Normochromic normocytic anemia was observed in males treated with AEL 300 mg/kg and AEB 600 and 1200 mg/kg as well as in females treated with AEB 300 and 1200 mg/kg. The kidney of all treated animals showed moderate inflammation and a few hemorrhagic points. In sub chronic assay, treatment with AEL 600 mg/kg, AEL 1200 mg/kg and AEB 1200 mg/kg caused hyper excitability in females that was not reversed. Treatments also had impact on weight gain and the relative weight of males’ brain was increased on group treated with AEL 300 mg/kg, AEB 300 and AEB 1200 mg/kg. Although changes in hematological parameters were not observed, serum creatinine levels were significantly higher in males treated with AEB 300 mg/kg. Besides, the heart of all treated animals showed intense hyperemia. Preliminary phytochemical analysis revealed the presence of flavonoids, tannins and phenolic compounds. Conclusions Toxicity signs were mainly observed after treatment with AEL and AEB at the two highest tested doses (600 and 1200 mg/kg), suggesting that the extracts are relatively safe at its effective dose (300 mg/kg). However, alterations on hematological and biochemical parameters and on the kidney and heart of the animals were not closely related with the dose, implying caution on its use. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Corn silk or the stigma of Zea mays L. has traditionally been used in weight loss stimulation and treatment of cystitis, urinary infections and obesity. Purple corn silk, rich of polyphenolic substances, was reported on anti-diabetic and anti-obesity effect in animal studies. However, scientific evidence on mechanisms and targets of action of purple corn silk related to adipocyte life cycle has been limited. Aim of study To determine phytochemical compositions and investigate anti-obesity potential of the purple corn silk focusing on interruption of adipocyte life cycle; effect on pre-adipocyte proliferation, adipogenesis, adipocyte lipolysis, and apoptosis. Materials and methods The ethanolic purple corn silk extract (PCS) was prepared and investigated for phytochemical compositions by LC/MS/MS technique and anti-obesity potential using murine 3T3-L1 cell line. Using methyl thiazole tetrazolium (MTT) assay, the effects on pre-adipocytes and adipocyte viability and on pre-adipocytes proliferation at 24-, 48-, and 72-h incubation period were evaluated. In addition, anti-adipogenesis via inhibition on adipocyte differentiation and reduction of total lipid accumulation was evaluated using Oil Red O staining and spectrophotometric methods, respectively. The lipolysis effect was determined by measurement of glycerol released content using glycerol test kit after 48-h treatment of PCS to adipocytes. Apoptosis inductive effect was done by using 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining method. Results The polyphenols including anthocyanins, quercetin and phenolic acids and derivatives were found as the major chemical compositions of the PCS. With multiple-stages interruption on the adipocyte life cycle, anti-obesity effect of PCS was interestingly demonstrated. When compared to the control, the PCS at concentration range between 250–1000 μg/mL showed anti-adipogenesis effect as expressing of significant inhibition on pre-adipocyte proliferation at all incubation period (43.52±5.28 – 75.51±9.09%) and significant decreasing of total lipid accumulation at concentration of 500 μg/mL (80.22±6.58%) and 1000 μg/mL (69.62±5.42%). Moreover, the PCS exhibited lipolysis and apoptosis inductive effect with dose dependent manner and significance at concentration of 1000 μg/mL by increase of released glycerol content (173.88±6.13% of the control) and of nuclei condensing and apoptotic bodies (with relative apoptosis induction as 131.74±1.64% of the control). Conclusion Our data has evidenced the anti-obesity potential of PCS related interruption at multiple stages of adipocyte life cycle. Its potency was attributed to inhibition on adipocyte proliferation and adipogenesis as well as induction on lipolysis and apoptosis at high concentration. However, further in vivo investigation should be considered to insist the possibility in applications of PCS in prevention and treatment of obesity. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown. Aim of the study To investigate the chemical profiles and effects of CKF on IBS model. Materials and methods The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS). On colon irritation induced rat neonates IBS model, the influence of CKF on neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT), were measured by ELISA, and the effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores. In addition, the activities of CKF against acetic acid-induced nociceptive responses and prostigmin methylsulfate triggered intestinal propulsion in mice were also evaluated. Results 80 components were identified or tentatively assigned from CKF, including 11 alkaloids, 20 flavanoids, 4 monoterpenoids, 9 iridoid glycoside, 9 phenylethanoid glycosides, 10 chromones, 7 organic acid, 3 coumarins, 2 triterpene and 5 other compounds. On IBS rat model, CKF was observed to reduce AWR scores and levels of SP, CGRP, VIP and 5-HT. Moreover, CKF reduced the acetic acid-induced writhing scores at all dosages and reduced the intestinal propulsion ration at dosage of 7.5 and 15.0 g/kg/d. Conclusions CKF could alleviate the symptoms of IBS by modulating the brain–gut axis through increasing the production of neuropeptides such as CGRP, VIP, 5-HT and SP, releasing pain and reversing disorders of intestinal propulsion. Berberine, paeoniflorin, acteoside, flavonoids and chromones may be responsible for the multi-bioactivities of CKF. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance To best of our knowledge this is the first quantitative ethno-medicinal study with the aim of documenting the indigenous knowledge and practices of using plants for malarial therapy in Soon Valley, Khushab, Pakistan. In this Valley, malaria is among the major public health problems but, until now, the population still mostly relies on herbal medicine for treatment. Materials and methods Ethno-medicinal data were documented from 63 informants by using semi-structured questionnaires and interviewing the informants about their knowledge of plants regarding malaria and related symptoms. Documented data were evaluated using the quantitative ethno-botanical indices of frequency citation (FC), relative frequency of citation (RFC), percentage of respondents having knowledge (PRK) and Jaccard index (JI). Results A total of 70 plant species belonging to 62 genera and 34 families were recorded as anti-malarial in the study area. Solanaceae was found to be the most cited family with 7 species, followed by Fabaceae, Rutaceae and Lamiaceae with 5 species each. Ocimum americanum and Solanum incanum were the species with the highest relative frequency of citation (RFC =0.25 each) and percentage of respondents having knowledge (PRK =25.4% each), followed by Grewia tenax (RFC =0.23, PRK =23.8%), which indicates that these plants are the best species with anti-malarial properties. The most highly cited life form was found to be herbs (56%). The dominant plant part used in preparations were leaves (49%). The main mode of utilization was decoction (47%) followed by infusion (29%). In comparison, maximum similarity index is found in our study with JI (16.83) followed by (13.13). Similarity percentage of plants uses ranges from 0.81 to 16.83 while dissimilarity percentage varies from 0% to 17.65%. Conclusions To the best of our knowledge seven plant species, viz. Withania coagulans , Fagonia cretica , Carthamus oxyacantha, Ehretia obtusifolia, Helianthus annuus, Olea ferruginea and Vitex trifolia , are reported from this region for the first time for the treatment of malaria. This first ethno-medicinal study highlights potential sources for the development of new antimalarial drugs from indigenous knowledge of medicinal plants found in the Soon Valley, Pakistan. Such investigations could be a subject for in vitro and in vivo anti-plasmodial screening to develop new plant-based antimalarial drugs and can also be evaluated for other biological activities and novel drug discoveries. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties. Aim of the study The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic. Material and methods The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i.e., formalin and transient receptor potential (TRP) channels agonists]. We also verified the effects of EOHs on locomotor activity and motor performance in mice. Finally, we investigate the involvement of central afferent C-fibers with EOHs analgesic effect. Results EOHs presented antinociceptive effect at 300 and 1000 mg/kg on formalin-induced pain behavior model, presenting 50% and 72% of inhibition during the first phase (ED 50 =292 mg/kg), and 85% and 100% during de second phase (ED 50 =205 mg/kg), respectively. Temperature of the hind paw was reduced by EOHs treatment in a dose-dependent manner; oedema was diminished only by EOHs 1000 mg/kg. EOHs does not impaired locomotor activity or motor performance. For mice injected with capsaicin, a TRPV1 activator, EOHs (1000 mg/kg, ED 50 =660 mg/kg) showed decreased (63%) nociceptive behavior. When injected with cinnamaldehyde (TRPA1 activator), mice treated with EOHs showed 23%, 43% and 66% inhibition on nociceptive behavior (100, 300 and 1000 mg/kg, respectively; ED 50 402 mg/kg). When mice were injected with menthol (TRPM8 activator), EOHs showed 29%, 59% and 98% inhibition of nociceptive behavior (100, 300 and 1000 mg/kg, respectively; with ED 50 =198 mg/kg. Finally, when desensitized mice were injected with menthol, EOHs (300 mg/kg) does not show antinociceptive effect. Conclusions This study demonstrated the efficacy of EOHs on experimental models of nociception. We have found the involvement of TRP channels V1, A1 and M8 with EOHs activity, which was remarkably potent and efficient in inhibiting pain evoked by menthol, a TRPM8 channel activator. TRPM8 channels from TRPV1+ C-fibers, but not TRPM8+ C-fibers nor TRPM8+ Aδ mechanosensory fibers, mediate EOHs analgesic effects. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Many Chinese medicinal materials (CMMs) have changed over centuries of use, particularly in terms of their botanical identity and processing methods. In some cases, these changes have important implications for safety and efficacy in modern clinical practice. As most previous research has focused on clarifying the evolution of CMMs by analyzing traditional Chinese materia medica (“ bencao ”) literature, assessments of historical collections are needed to validate these conclusions with material evidence. Aim of the study Historical collections of Chinese medicines reveal the market materials in circulation at a given moment in time, and represent an underexploited resource for analyzing the evolution of Chinese herbal medicines. This study compares specimens from a rare collection of CMMs from the 1920s with contemporary market materials; by highlighting examples of changes in botanical identity and processing that remain relevant for safe clinical practice in the modern era, this work aims to stimulate further research into previously unexplored historical collections of Chinese medicines. Materials and methods 620 specimens of CMMs that were collected from Chinese pharmacies in the Malay peninsula in the 1920s were examined macroscopically and compared with current pharmacopoeia specifications and authentic contemporary samples. These historical specimens, which are stored in the UK in the Economic Botany Collections (EBC) of Royal Botanic Gardens Kew, were morphologically examined, photographed, and compared to authentic CMMs stored at the Bank of China (Hong Kong) Chinese Medicines Center at Hong Kong Baptist University, as well as authentic herbarium-vouchered specimens from the Leon Collection (LC) at the Kew EBC. Case studies were selected to illustrate examples of historical changes in botanical identity, used plant parts, and processing methods. Results This investigation confirmed that confusion due to shared common names and regional variations in the botanical identity of certain CMMs has been a persistent issue over time. Additionally, historical changes in processing methods and the plant parts used were observed for some CMMs. In some cases, these changes have direct implications for the safe clinical practice of Chinese medicine. Conclusions This preliminary assessment illustrated the significant potential of collections for clarifying historical changes in CMMs. More research is needed to investigate pre-modern collections of CMMs, including a more comprehensive assessment of the holdings in the Kew EBC and other European collections that have not yet been explored from the perspective of Chinese medicine. [ABSTRACT FROM AUTHOR]

Ethenopharmacological relevance India has a long tradition of practicing Ayurvedic medicine not only for human ailments, but also for the management of livestock in the form of ethno-veterinary practices. Asian elephant is a significant part of Indian culture, and ethno-veterinary practices have extended to manage and cure various ailments of Asian elephant in captivity. Much of this knowledge has been lost in the light of modern practices. Aim of the study This study is aimed at documenting the existing knowledge on ethno-veterinary medicines practiced by elephant keepers ( mahouts ) in Tamil Nadu and Puducherry. Materials and methods The study was carried out between June 2015 and February 2016 employing a questionnaire survey among 50 selected informants ( mahouts ) with traditional knowledge on plants in veterinary medicine. Information was elicited from the informants on various diseases prevailing among captive elephants and the traditional treatment employed by them. Results In total, the study documented 53 plant species belonging to 29 families being used as medicine for 23 types of ailments prevailing among captive elephants. Ferula assa-foetida, Zingiber officinale, Piper longum, P. nigrum, Cuminum cyminum, Trachyspermum roxburghianum and Carum bulbocastanum were the most commonly used plants either independently or in combination. Among them, Ferula assa-foetida (12.4%) and Zingiber officinale (10.4%) had the highest usage. Of the 23 diseases reported, constipation was the most common ailment (14.6%) followed by bloating (8.7%) and flatulence (8.7%). Conclusion Documentation of this indigenous knowledge is valuable for the communities concerned, both at present and in future and for scientific consideration for wider use of traditional knowledge in treating captive elephants. The study has identified 53 medicinal plants to treat various ailments among captive elephants in southern India. The most frequently used plants in the captive elephant health care practice are F. assafoetida, Z. officinale, P. longum and P.nigrum . Among the 29 families, Apiaceae and Piperaceae are widely used. The leaves are the most useful part of the plants, while paste is the widely used form of preparation. The present findings show that mahouts have wide knowledge about elephant diseases and their treatment using herbal medicine. A more detailed investigation should be designed on priority to document the dying art of ethno-veterinary practices for the long-term conservation of the Asian elephant. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aloe vera is one of the most important medicinal plants in the world with applications in the cosmetic industry and also in the tonic or health drink product market. Different parts of Aloe ferox and Aloe marlothii are used as traditional medicines for different applications. Although wound healing has been shown for certain aloe gel materials ( e.g. A. vera ) previously, there are conflicting reports on this medicinal application of aloe leaf gel materials. Aim of the study The present study aimed at determining the wound healing properties of the gel and whole-leaf materials of Aloe vera , Aloe ferox and Aloe marlothii, as well as their cytotoxic effects on normal human keratinocyte cells (HaCaT). Materials and methods Nuclear magnetic resonance spectroscopy was used to chemically fingerprint the aloe gel and whole-leaf materials by identifying characteristic marker molecules of aloe gel and whole-leaf materials. An MTT assay was performed to determine the cytotoxicity of the various aloe whole-leaf and gel materials on HaCaT cells. Wound healing and in vitro cell migration were investigated with HaCaT cells by means of the CytoSelect™ assay kit. Results The in vitro wound healing assay suggested that all the aloe gel and whole-leaf materials examined, exhibited faster wound healing activity than the untreated control group. After 48 h, all the aloe gel and whole-leaf materials almost completely caused full wound closure, displaying 98.07% ( A. marlothii whole-leaf), 98.00% ( A. vera gel), 97.20% ( A. marlothii gel), 96.00% ( A. vera whole-leaf), 94.00% ( A. ferox gel) and 81.30% ( A. ferox whole-leaf) wound closure, respectively. It was noteworthy that the gel materials of all the three aloe species exhibited significantly faster (p<0.05) wound healing actions when compared to their respective whole-leaf materials at 32 h. Conclusion The gel and whole-leaf materials of A. vera , A. ferox and A. marlothii have shown the ability to heal wounds at a faster rate and to a larger extent than untreated keratinocytes. The MTT assay results suggested that the gel and whole-leaf materials of all the selected Aloe species showed negligible toxicity towards the HaCaT cells. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Plants used in the traditional medicine of Europe to treat memory dysfunction and/or to enhance memory were investigated for activity against the underlying mechanisms of Alzheimer's disease. Aim of the study To investigate 35 ethanolic extracts of plants, selected using an ethnopharmacological approach, for anti-amyloidogenic activity as well as an ability to inhibit the enzymatic activity of acetylcholinesterase. Materials and methods The anti-amyloidogenic activity of the extracts against amyloid beta was investigated by Thioflavin T fibrillation assays and the ability to inhibit the enzymatic activity of acetylcholinesterase was evaluated monitoring the hydrolysis of acetylthiocholine Results Under the experimental conditions investigated, extracts of two plants, Carum carvi and Olea sylvestris , inhibited amyloid beta fibrillation considerably, eight plant extracts inhibited amyloid beta fibrillation to some extent, 16 plant extracts had no effect on amyloid beta fibrillation and nine extracts accelerated fibrillation of amyloid beta. Furthermore, five plant extracts from Corydalis species inhibited the enzymatic activity of acetylcholinesterase considerably, one plant extract inhibited the enzymatic activity of acetylcholinesterase to some extent and 29 plant extract had no effect on the enzymatic activity of acetylcholinesterase. Conclusions An optimal extract in this study would possess acetylcholinesterase inhibitory activity as well as anti-amyloidogenic activity in order to address multiple facets of Alzheimer's disease, until the molecular origin of the disease is unraveled. Unfortunately no such extract was found. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Atherosclerosis (AS) is the major pathogenic component of coronary artery and cardiovascular disease. Studies have increasingly focused on natural medicines that have lipid-lowering, anti-inflammatory, and endothelial–protection activities. Black mulberry fruits are traditionally used in Uyghur folk medicine for the prevention and treatment of cardiovascular diseases in southern Xinjiang region of China. However, its underlying mechanisms remain unknown. Thus, our objective was to explore the effects and underlying mechanisms of ethanol extract of black mulberry (EEBM) in experimental atherosclerotic rats. Materials and methods The black mulberry fruit was extracted with acid ethanol and chromatographed on an AB-8 macroporous resin to obtain EEBM. Atherosclerotic rats were divided into five groups: normal, model, model plus simvastatin (5 mg/kg d·body weight), and model plus low-dose and high-dose EEBM groups (105 and 210 mg/kg d·body weight, respectively). Serum lipid profiles were measured by an automatic biochemistry analyser. The activities of anti-oxidative enzymes were determined using the chemical colorimetric method. Pathological changes in liver and arteries were examined by hematoxylin and eosin (H&E), and the intima-media thickness was measured. Results The high-dose EEBM group showed significantly reduced total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels, as well as atherogenic index. Furthermore, treatment with high-dose EEBM markedly decreased malondialdehyde content and enhanced anti-oxidative enzyme activities. Histopathological examination showed that EEBM attenuated hepatic steatosis and reduced intima-media thickness and arterial atherosclerotic lesions in atherosclerotic rats. These results suggest that EEBM suppressed atherosclerosis development in atherosclerotic rats by regulating lipid metabolism abnormalities, enhancing anti-oxidative activities, and reducing atherosclerotic lesions, which could be attributed to anthocyanins (23.75%), or the cooperative action of anthocyanins, polyphenols (2.95%), and flavonoids (0.94%). [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Spatholobi Caulis is a traditional blood-activating and stasis-dispelling herb medicine, which has been used to treat diseases related to blood stasis syndrome (BSS) by inhibiting platelet aggregation, stimulate hematopoiesis, etc. It has been demonstrated that pro-angiogenesis could improve BSS. However, the pro-angiogenic activity of Spatholobi Caulis was not well elucidated Aim of study To determine the potential pro-angiogenic activity of Spatholobi Caulis and elucidate its underlying mechanism. The active fractions of Spatholobi Caulis were further screened. Material and methods Gelatin precipitation and reversed-phase liquid chromatography (RPLC) were used to purify the methanol extracts of Spatholobi Caulis , respectively. The RPLC was also used to prepare fractions. Total flavonoids of purified methanol extracts of Spatholobi Caulis (PSC) were determined using ultraviolet spectrophotometry. The morphological observation of subintestinal vessel plexus (SIVs) and tyrosine kinase inhibitor II (VRI)-induced intersegmental blood vessels (ISVs) loss in transgenic zebrafish Tg(fli-1a: EGFP)y1 were selected to evaluate the pro-angiogenic activity of PSC in vivo. Cell proliferation by MTT assay and cell migration assay were used to evaluate the pro-angiogenesis effect of PSC in human umbilical vein endothelial cells (HUVECs) in vitro . Both zebrafish and HUVECs were used in screening active fractions of PSC. The mechanism of PSC promoting angiogenesis were studied by real-time PCR in zebrafish and western blotting in HUVECs. Results Co-treatment PSC dramatically rescued VRI-induced ISVs loss in zebrafish embryos in a dose-dependent manner and 80% of the defective vascular recovered at the concentration of 30 μg/ml compared with VRI-only group. PSC also concentration-dependently increased average sprouting number and diameter of SIVs in zebrafish embryo. Real-time PCR assay proved that PSC significantly restored the down regulation of VEGFRs including Flt-1, Kdr and Kdrl induced by VRI in zebrafish (P<0.001). Furthermore, PSC not only promoted proliferation and migration of normal HUVECs but also ameliorated VRI-induced HUVECs cytotoxicity. Western blotting assay showed that co-treatment of PSC increased the expression of VEGFRs and phosphorylation of MAPKs which decreased by VRI treatment. In addition, quality evaluation experiments showed that the content of total flavonoids of PSC reached 56.36% and the main pro-angiogenic fractions of PSC were F3, F4 and F5 both in zebrafish and HUVECs. Conclusions Our data demonstrated that PSC presented pro-angiogenic activity both in zebrafish and HUVECs, and principal pro-angiogenic active components were likely flavonoids. Thus, the current study provided evidence for the clinical usage of Spatholobi Caulis in promoting blood circulation and removing stasis in traditional Chinese medicine (TCM). [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Complications of type 2 diabetes (T2D) include stroke, which is a cerebrovascular disturbance characterized by reduced blood flow in the brain, leading to death or physical disability. Chinese herbal medicine (CHM) has been widely used in ancient China for the treatment of diabetes and stroke by supplementing Qi and activating blood circulation. Aim of the study This study aimed to investigate the frequencies and patterns of CHM treatment for stroke patients with T2D and the outcomes of long-term use in Taiwan. Materials and methods We identified 3079 stroke patients (ICD-9-CM: 430–438) with T2D. We allocated 618 stroke patients, matched for age, gender, and T2D-to-stroke duration, to both CHM and non-CHM groups. Chi-square test, conditional multivariable logistic regression, Kaplan-Meier method, and the log-rank test were used in this study. Results The CHM group was characterized by more cases of chronic obstructive pulmonary disease, ulcer disease, hyperlipidemia, tobacco use, and higher income. The cumulative survival probability was higher in the CHM group ( P <0.001, log rank test); after adjusting for comorbidities, income, and urbanization level, this group also exhibited a lower mortality hazard ratio (0.37, 95% confidence interval [0.25–0.55]). Shu-Jing-Huo-Xue-Tang, Xue-Fu-Zhu-Yu-Tang, and Du-Huo-Ji-Sheng-Tang; and Dan-Shen, Niu-Xi, and Yan-Hu-Suo represented the top three formulas and herbs, respectively. Conclusion The use of CHM as adjunctive therapy may improve the overall survival (OS) of stroke patients with T2D. The list of the comprehensive herbal medicines that they used might be useful in future large-scale, randomized clinical investigations of agent effectiveness, safety, and potential interactions with conventional treatments in stroke patients with T2D. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Dipsacus asper Wall. ex C.B. Clarke (DA) is an effectively traditional Chinese medicine for treating osteoporosis and bone fracture. Until now, studies on pharmacological mechanism of DA mostly centered on cell and gene level, little is known about its metabolic signatures. The aim of this study is to investigate the anti-osteoporosis effects of crude and wine-processed DA by global and untargeted metabolic profiling of rats serum, liver and kidney derived from sham, model and treated groups. Method A total of 25 female Wistar rats were divided into five groups: sham group, model group, E2, crude and wine-processed DA treated group. The treatment rats were orally administered 17 β -estradiol, crude and wine-processed DA extract at a therapeutic dose once daily throughout the experimental period, while sham group and model group were orally gavaged approximately volume of saline solution. After 16 weeks, all serum, liver and kidney samples of five groups were collected and their metabolomic alterations were monitored by gas chromatography–mass spectrometry (GC–MS). The resulting dataset was analyzed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The identification of all potential biomarkers was performed using reference standard or NIST library. Moreover, clinical chemistry and biomechanical analysis were also performed to ensure the success of the osteoporosis model and to validate the anti-osteoporosis effect of crude and wine-processed DA. Results Clear separation trend among sham, model and treatment group was observed in PCA score plot. The anti-osteoporosis effect of DA and wine-processed DA can be indicated in PLS-DA score plots. A total of 80 and 74 metabolite biomarkers were identified for DA and wine-processed DA treated groups, respectively. Pathway analysis revealed that phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, methane metabolism, glycine, serine and threonine metabolism, galactose metabolism were the major intervened pathways. Compared with model group, levels of all biomarkers were gradually restored to normal after administration of DA and wine-processed DA. Conclusion The anti-osteoporosis effect of DA and wine-processed DA has been reliably confirmed by the metabolomics approach. The osteoporosis might be prevented by DA and wine-processed DA via intervening amino acid metabolism, carbohydrate metabolism and energy metabolism in vivo in rats. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Cutaneous and mucocutaneous leishmaniasis are neglected tropical diseases that occur in all intertropical regions of the world. Amazonian populations have developed an abundant knowledge of the disease and its remedies. Therefore, we undertook to review traditional antileishmanial plants in Amazonia and have developed new tools to analyze this somewhat dispersed information. Material and methods A literature review of traditional remedies for cutaneous/mucocutaneous leishmaniasis in the Amazon was conducted and the data obtained was used to calculate distribution indexes designed to highlight the most relevant uses in Amazonia. The cultural distribution index represents the distribution rate of a given taxon among different cultural groups and was calculated as the ratio of the number of groups using the taxon to the total number of groups cited. The geographical distribution index allowed us to quantify spatial distribution of a taxon’s uses in Amazonia and was calculated geometrically by measuring the average distance between the points where uses have been reported and the barycenter of those points. The general distribution index was defined as an arithmetic combination of the previous two and provides information on both cultural and spatial criteria. Results 475 use reports, concerning 291 botanical species belonging to 83 families have been gathered depicted from 29 sources. Uses concern 34 cultural groups. While the use of some taxa appears to be Pan-Amazonian, some others are clearly restricted to small geographical regions. Particular attention has been paid to the recipes and beliefs surrounding treatments. Topical application of the remedies dominated the other means of administration and this deserves particular attention as the main treatments against Neotropical leishmaniasis are painful systemic injections. The data set was analyzed using the previously defined distribution indexes and the most relevant taxa were further discussed from a phytochemical and pharmacological point of view. Conclusions The Amazonian biodiversity and cultural heritage host a fantastic amount of data whose systematic investigation should allow a better large-scale understanding of the dynamics of traditional therapies and the consequent discovery of therapeutic solutions for neglected diseases. Distribution indices are indeed powerful tools for emphasizing the most relevant treatments against a given disease and should be very useful in the meta-analysis of other regional pharmacopeia. This focus on renowned remedies that have not yet benefitted from extended laboratory studies, could stimulate future research on new treatments of natural origin for leishmaniasis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Many patients with gastric cancer seek traditional medicine consultations in Asian countries. This study aimed to investigate the prescription of Chinese herbal medicine (CHM) and its benefits for the patients with gastric cancer in Taiwan. Methods From the Registry for Catastrophic Illness Patients Database, we included all patients with gastric cancer whose age at diagnosis was ≥18 from 1997 to 2010 in Taiwan. We used 1:1 frequency matching by age, sex, Charlson comorbidity score, treatment and index year to compare the CHM users and non-CHM users. We used the Cox regression model to compare the hazard ratios (HR) for the risk of mortality and the Kaplan–Meier curve for the survival time. Results There was a total of 1333 patients in the CHM-cohort and 44786 patients in the non-CHM cohort. After matching, we compared 962 newly diagnosed CHM users and 962 non-CHM users. Adjusted HRs (aHR) were higher among patients of above 60-year-old group, with a Charlson Comorbidity Index score ≥2 before the index date, and those who need surgery combined with chemotherapy or radiotherapy. CHM users had a lower HR of mortality risk (adjusted HR: 0.55, 95% CI: 0.48–0.62). Compared to the non-CHM users, the aHR among CHM-users is 0.37 (95% CI:0.2–0.67) for those who used CHM more than 180 days annually. The Kaplan–Meier curve revealed that the survival probability was higher for complementary CHM-users. Bai-Hua-She-She-Cao (Herba Hedyotidis Diffusae) was the most commonly used single herb and Xiang-Sha-Liu-Jun-Zi-Tang was the most commonly used herbal formula among CHM prescriptions. Conclusions Complementary CHM improves the overall survival among patients with gastric cancer in Taiwan. Further ethnopharmacological investigations and clinical trials are required to validate the efficacy and safety. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The root of Saussurea costus ( Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD. Materials and methods HaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively. After lesions developed, we topically applied 1,3-butylen glycol (vehicle; control), SC (30%), TOL (30%), or SC (15%)+TOL (15%) to the skin lesions for 5 weeks. The normal-control was not exposed to DNCB. The skin thickness, mast cell infiltration, serum immunoglobulin E (IgE) and IgG1 and gene expressions of interleukin (IL)−4, IL-13, and IFN-γ in the dorsal skin and HaCaT cells were measured. Results Chlorogenic acid (129.6±10.2 μg/g) for SC and catechin and apigenin (93.4±13.2 and 16.9±1.3 μg/g, respectively) for TOL were used as indicator compounds for the strength of the extracts. SC+TOL decreased the expression of protease-activated receptor-2 and ICAM-1 and the release of TNF-α and IL-6 in HaCaT cells activated by 3 μg/mL house mite extracts in comparison to either of SC or TOL alone. In Nc/Nga mice challenged with DNCB, SC+TOL synergistically attenuated clinical symptoms of AD such as erythema, hemorrhage, edema, excoriation and dryness in the dorsal skin better than either SC or TOL alone. Histological analysis of the dorsal skin also showed that SC+TOL treatment significantly and additively decreased the inflammatory cellular infiltrate, including mast cells and eosinophils in comparison to either of SC or TOL. SC+TOL also decreased serum IgE and IgG1 levels and the expression of IFN-γ, IL-4, and IL-13 mRNA in dorsal skin in DNCB-treated Nc/Nga mice. Conclusion SC+TOL relieved the symptoms of AD by reducing pro-inflammatory activity and over-activated immune responses. These data suggest that SC+TOL may be an effective alternative intervention for the management of AD. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The aim of this study was to collect and document information concerning the medicinal plants used by indigenous people and traditional healers in the south of Kerman Province, Iran. Materials and methods Overall, 64 informants between the ages of 30 and 89 were interviewed about the modes of application and consumption of medicinal plants in the region. Quantitative analysis was conducted that included informant consensus factor (ICF), use value (UV), relative frequency of citation (RFC) and cultural importance index (CI). Results and discussion In the current study, a total of 115 medicinal plants in 41 families were reported in the south of the Kerman region. Apiaceae, Asteraceae and Lamiaceae (with 14 species each) were the families with the most medicinal plants. The most frequently used plant parts were leaves at 26.17% and aerial parts (23.49%). Decoction (53%), liniment (23%) and infusion (9%) were the most common preparation methods. The highest UVs were obtained from the following medicinal plants: Amygdalus eburnea Spach, Genista tinctoria L., Calotropis procera (Aiton) Dryand., Fortuynia garcinii (Burm.f.) Shuttlew. and Cerasus mahaleb (L.) Mill. The ICF results indicated that cold-flu and fever were the most common diseases (0.67) in the south of Kerman. Conclusion Based on the current study, the south of Kerman has many potential medicinal plants, and these plants should be the focus of future research. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The roots, stem and leaves of Morinda lucida are used in some African countries as treatment against different types of fevers including yellow fever, malaria, trypanosomiasis and feverish conditions during child birth. Aim of the study To determine the in vitro cell toxicity and anti-malarial activity of the extracts of stem bark of M. lucida and to identify the secondary metabolites in the extract that may be responsible for this activity. Materials and methods The cell toxicity studies of crude extract [dichloromethane (DCM): Methanol (MeOH) in a ratio of1:1 (v/v)] as well as compounds isolated from the same extract were carried out using human cervix adenocarcinoma cells (HeLa cells); while the anti-malarial activities of the same samples were performed against Plasmodium falciparum strain 3D7 using the parasite lactate dehydrogenase (pLDH) assay. The isolation of the active compounds was carried out using chromatographic techniques (column and thin layer chromatography) where as mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR) as well as 1D- and 2D- nuclear magnetic resonance (NMR) analyses were employed in the characterisation and identification of the isolated secondary metabolites. Results The pLDH and cell toxicity assays for the crude extract and the fractions of M. lucida indicated that some fractions reduced the malaria parasite viability by approximately 50% at 100 μg/mL and they were not significantly cytotoxic. An IC 50 done on the crude extract gave a value of 25 μg/mL. The % cell viability for the crude extract in cell toxicity assay remained at 100%. Seven chemical constituents i.e. asperuloside ( 1 ), asperulosidic acid ( 2 ), stigmasterol ( 3a ), β-sitosterol ( 3b ), cycloartenol ( 3c ), campesterol ( 3d ) and 5,15-O-dimethylmorindol ( 4 ) were isolated from the DCM-MeOH extract of stem bark. The isolated compounds tested were not that active by themselves individually at 20 μM but their activities were increased when the isolated compounds were combined. As seen when compounds 2, 3 and 4 (% viability: 93, 123 and 101 respectively) were combined yielding an IC 50 value of 17 μM. Furthermore, this is the first report of compounds 1, 2, 3c, 3d and 4 isolated from M. lucida . Conclusion The crude extract completely suppressed the growth of P. falciparum . This indicates that the crude extract contains many compounds that might be acting in synergy. The observed activity of the crude extract and the samples containing a mixture of different compounds support the traditional use of M. lucida for the treatment of malaria. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Toads belonging to genus Rhinella are used in Paraguayan traditional medicine to treat cancer and skin infections. Aim of the study The objective of the study was to determine the composition of venoms obtained from three different Paraguayan Rhinella species, to establish the constituents of a preparation sold in the capital city of Paraguay to treat cancer as containing the toad as ingredient, to establish the effect of the most active Rhinella schneideri venom on the cell cycle using human breast cancer cells and to assess the antiprotozoal activity of the venoms. Methods The venom obtained from the toads parotid glands was analyzed by HPLC-MS-MS. The preparation sold in the capital city of Paraguay to treat cancer that is advertised as made using the toad was analyzed by HPLC-MS-MS. The effect of the R. schneideri venom and the preparation was investigated on human breast cancer cells. The antiprotozoal activity was evaluated on Leishmania braziliensis , L . infantum and murine macrophages. Results From the venoms of R. ornata , R. schneideri and R. scitula , some 40 compounds were identified by spectroscopic and spectrometric means. Several minor constituents are reported for the first time. The preparation sold as made from the toad did not contained bufadienolides or compounds that can be associated with the toad but plant compounds, mainly phenolics and flavonoids. The venom showed activity on human breast cancer cells and modified the cell cycle proliferation. The antiprotozoal effect was higher for the R. schneideri venom and can be related to the composition and relative ratio of constituents compared with R. ornata and R. scitula . Conclusions The preparation sold in the capital city of Paraguay as containing the toad venom, used popularly to treat cancer did not contain the toad venom constituents. Consistent with this, this preparation was inactive on proliferation of human breast cancer cells. In contrast, the toad venoms of Rhinella species altered the cell cycle progression, affecting the proliferation of malignant cells. The findings suggest that care should be taken with the providers of the preparation and that the crude drug present a strong activity towards human breast cancer cell lines. The antiprotozoal effect of the R. schneideri venom was moderate while the venom of R. ornata was devoid of activity and that of R. scitula was active at very high concentration. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The root extract of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) is traditionally used in the management of pain and fever. However, little scientific data exists in literature to support its use. Aim of study The present study evaluated the anti-nociceptive and antipyretic properties of the hydroethanolic extract of the roots of Albizia zygia in animal models. Materials and methods The analgesic effects were investigated in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (tail-immersion test) and mechanical (carrageenan-induced hyperalgesia) pain models. Possible mechanisms of anti-nociception were also assessed with antagonists in the formalin test. The anti-pyretic effect was evaluated using the baker yeast-induced pyrexia model in young rats. Results The extract (30–300 mg/kg, p.o .) and positive controls, diclofenac (3–30 mg/kg, i.p.) and morphine (1–10 mg/kg, i.p.), significantly (at least P <0.01) attenuated acetic acid-induced visceral pain, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical hyperalgesia in animals. The anti-nociceptive effect of the extract was reversed (at least P <0.05) by the pre-emptive administration of naloxone and atropine; the administration of theophylline, however, exhibited no significant ( P >0.05) inhibition of anti-nociception. The extract (30–300 mg/kg, p.o ) and paracetamol (15–150 mg/kg, p.o. ) both reversed yeast-induced pyrexia in rats with ED 50 values of 48.59±2.59 and 26.19±1.33 mg/kg respectively. Conclusion The findings indicate that the extract possesses significant anti-nociceptive and antipyretic effects which justify its traditional use in the management of pain and fever. Also, anti-nociceptive effect of the extract involves opioidergic and muscarinic cholinergic mechanisms. [ABSTRACT FROM AUTHOR]

Introduction and background In recent decades diabetes mellitus has become a considerable health problem in countries like Sri Lanka and results in an increasing economic burden hampering the social and economic development of these countries. About 60% to 70% of the rural population in Sri Lanka rely on indigenous medicinal systems as their main source for primary health care. Siddha (Tamil) Medicine is one of the four Sri Lankan traditional medicinal systems and it is practised mostly in the eastern and northern provinces of Sri Lanka where the majority of Tamils reside. Aim The foundation of this study is a documentation of plant species recorded in historical and modern Sri Lankan Siddha Medical documents used to treat diabetes. Based on the systematic documentation and analysis of Siddha concepts about diabetes and its signs and preparations used to treat diabetes in Sri Lankan Siddha Medicine, the plant species included in these preparations (excluding globally or very widely used, very well studied species) were evaluated in terms of the current state-of-the-art about these species' pharmacology and effectiveness in order to lay a foundation for their further development. Method Historic and modern Sri Lankan university texts books in Tamil were used as sources for information on diabetes Siddha concepts and antidiabetic Sri Lankan Siddha Medicine preparations. Information on the known antidiabetic effects of extracts and compounds obtained from these species were used in order to assess the current state of the art of these species. Results and discussion Information of ingredients, preparation methods, amount of ingredients used, and dosages of 60 antidiabetic Sri Lankan Siddha Medicine preparations were obtained. Animal parts including marine organisms, inorganic substances, and plants are the three types of ingredients used. Overall 171 plant species in 73 families were documented. Senna auriculata (L.) Roxb. (Fabaceae) was identified as the most frequently cited species. Globally distributed and very well studied plants were excluded in the pharmacological and clinical literature review which includes 123 plant species. The majority (48%) of the plant species reviewed were studied up to in vivo level as the current maximum level of scientific evidence available. Followed by 41% of species have not been studied for antidiabetic activities or did not show antidiabetic activity. Moreover, 6% and 5% were studied up to in vitro and in clinical levels, respectively. The majority of the species were studied only in the models that represent type 1 diabetes. Conclusion This is the first study systematically assessing the importance of preparations and plants used in antidiabetic Sri Lankan Siddha Medicine preparations. Antidiabetic plants are a crucial health care resource in Sri Lankan Siddha Medicine. This study also identified a wide range of methodological problems in the studies conducted so far. More and better type 2 diabetes models should be employed in future studies. This comprehensive review creates the basis for a more systematic study of these local resources. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The plant Solanum xanthocarpum Schrad. & Wendl. (Solanaceae) is one of the members of the dashamula (ten roots) in Ayurvedic system of medicine. The stem and fruits are used as an antipyretic, antiasthmatic and is prescribed in skin infections and for relief in burning sensation in the feet accompanied by vesicular eruptions. Objective To scientifically validate the anti-psoriatic potential of Solanum xanthocarpum stem in Imiquimod-induced psoriatic mice model. Materials and methods Ethanolic stems extract of Solanum xanthocarpum (ESX) was first subjected to phytochemical screening and quantification of identified phytoconstituents, which was further standardized with the help of HPTLC using chlorogenic acid as a marker. The extract was then subjected to acute oral toxicity and skin irritability study for determining the safety profile of the extract. Imiquimod-induced psoriatic mouse model was then performed to check the efficacy of extract against psoriasis, where treatment was carried out for 15 days both topically (Gel at 2.5%, 5% and 10%) as well as orally (at 100, 200 and 400 mg/kg p.o.) and their Psoriasis Area Severity Index (PASI) was calculated. The study also included determination of levels of TNF-α, IL-1β, IL-6 and IL-17 in the animal tissues, which further included biochemical evaluations such as total collagen, hexosamine, hyaluronic acid DNA, protein antioxidant profiles such as lipid peroxidation, nitric oxide, superoxide dismutase and catalase along with histopathological studies of the tissues. Result ESX showed the presence of mainly phenols, tannins, flavonoids, alkaloids and carbohydrates, while chlorogenic acid was reported to be 3.49% w/w. The Imiquimod-induced psoriatic mouse model, depicted a potent anti-psoriatic activity of the extract both topical (10%) and oral (200 and 400 mg/kg p.o., as evident through PASI grading The effect was found to be more prominent in case of topically treated as compared to orally treated mice. The results also showed a significant inhibition in the expression of TNF-α, IL-1β, IL-6 and IL-17 in treated animal tissues and also showed significant restoration of the altered biochemical parameters along with reduced hyperkeratinisation as observed through histopathology. Conclusion The study scientifically justified the anti-psoriatic activity of the ESX, which may be attributed to inhibition in the expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-17. Further, the observed antioxidant, antimicrobial and cellular proliferative activities may act as a contributing factor in treatment of psoriasis, which may be attributed to the presence of chlorogenic acid along with other phytochemicals in combination. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Hawthorn ( Crataegus pinnatifida Bunge) leave have been used to treat cardiovascular diseases in China and Europe. Hawthorn leave flavonoids (HLF) are the main part of extraction. Whether hawthorn leave flavonoids could attenuate the development of atherosclerosis and the possible mechanism remain unknown. Materials and methods High-fat diet (HFD) mixed with HLF at concentrations of 5 mg/kg and 20 mg/kg were administered to apolipoprotein E (apoE) knock out mice. 16 weeks later, mouse serum was collected to determine the lipid profile while the mouse aorta dissected was prepared to measure the lesion area. Hepatic mRNA of genes involved in lipid metabolism were determined. Peritoneal macrophages were collected to study the impact of HLF on cholesterol efflux, formation of foam cell and the expression of ATP binding cassette transporter A1 (ABCA1). Besides, in vivo reverse cholesterol transport (RCT) was conducted. Results HLF attenuated the development of atherosclerosis that the mean atherosclerotic lesion area in en face aortas was reduced by 23.1% (P<0.05). In mice fed with 20 mg/kg HLF, Total cholesterol (TC) level was decreased by 18.6% and very low density lipoprotein cholesterol plus low density lipoprotein cholesterol (VLDLc+LDLc) level were decreased by 23.1% whereas high density lipoprotein cholesterol (HDLc) and triglyceride (TG) levels were similar compared to that of the control group. Peroxisome proliferator activated receptor alpha (PPARα) mRNA was increased by 31.2% (P<0.05) and 60.9% (P<0.05) in mice fed with 5 mg/kg and 20 mg/kg HLF respectively. Sterol regulatory element binding protein-1c (SREBP-1c) was decreased by 59.3% in the group of 20 mg/kg. Carnitine palmitoyl transferase 1 (CPT-1) mRNA level of 20 mg/kg group was induced 66.7% (P<0.05). Superoxide dismutase 1 and 2 (SOD1 and SOD2) mRNA were induced 25.4% (P<0.05) and 71.4% (P<0.05) while induced by 36.3% (P<0.05) and 73.2% (P<0.05) in group of 20 mg/kg. Glutathione peroxidase 3 (Gpx3) mRNA in the group of 20 mg/kg was induced by 96.7% (P<0.05). Hepatic hydroxymethylglutaryl CoA reductase (HMG-CoAR) expression was as same level as the control group while LDL receptor (LDLR) mRNA and protein were induced by 84.2% (P<0.05) and 98.8% (P<0.05) in group of 20 mg/kg. HLF inhibit the formation of foam cell by 27.9% (P<0.05) in the dosage of 25 μg/ml, and 33.3% (P<0.05) in the dosage of 50 μg/ml. HLF increased the reverse cholesterol transport (RCT) in vivo . Discussion and conclusion Hawthorn leave flavonoids can slow down the development of atherosclerosis in apoE knockout mice via induced expression of genes involved in antioxidant activities, inhibition of the foam cell formation and promotion of RCT in vivo , which implies the potential use in the prevention of atherosclerosis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The use of medicinal plants in Mexico has been documented since pre-Hispanic times. Nevertheless, the level of use of medicinal plants by health professionals in Mexico remains to be explored. Aim of the study To evaluate the use, acceptance and prescription of medicinal plants by health professionals in 9 of the states of Mexico. Materials and methods Direct and indirect interviews, regarding the use and acceptance of medicinal plants, with health professionals (n=1614), including nurses, physicians, pharmacists, and odontologists from nine states in Mexico were performed from January 2015 to July 2016. The interviews were analyzed with the factor the informant consensus (FIC). Results The information obtained indicated that 46% of those interviewed feel patients should not use medicinal plants as an alternative therapy. Moreover, 54% of health professionals, and 49% of the physicians have used medicinal plants as an alternative therapy for several diseases. Twenty eight percent of health professionals, and 26% of the physicians, have recommended or prescribed medicinal plants to their patients, whereas 73% of health professionals were in agreement with receiving academic information regarding the use and prescription of medicinal plants. A total of 77 plant species used for medicinal purposes, belonging to 40 botanical families were reported by the interviewed. The results of the FIC showed that the categories of diseases of the digestive system (FIC=0.901) and diseases of the respiratory system (FIC=0.898) had the greatest agreement. Conclusions This study shows that medicinal plants are used for primary health care in Mexico by health professionals. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Limonium brasiliense (Boiss.) Kuntze (Plumbaginaceae) is commonly known as “baicuru” or “guaicuru” and preparations of its dried rhizomes have been popularly used in the treatment of premenstrual syndrome and menstrual disorder, and as an antiseptic in genito-urinary infections. This study evaluated the potential antibacterial activity of rhizome extracts against multidrug–resistant bacterial strains using statistical mixture design. Materials and methods The statistical design of four components (water, methanol, acetone, and ethanol) produced 15 different extracts and also a confirmatory experiment, which was performed using water:acetone (3:7, v/v). The crude extracts and their ethyl-acetate fractions were tested against vancomycin–resistant Enterococcus faecium (VRE fm ), methicillin–resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae carbapenemase (KPC)–producing K. pneumoniae , all of which have been implicated in hospital and community–acquired infections. The dry residue, total polyphenol, gallocatechin and epigallocatechin contents of the extracts were also tested and statistical analysis was applied in order to define the fit models to predict the result of each parameter for any mixture of components. The principal component and hierarchical clustering analyses (PCA and HCA) of chromatographic data, as well as mass spectrometry (MS) analysis were performanced to determine the main compounds present in the extracts. Results The Gram-positive bacteria were susceptible to inhibition of bacterial growth, in special the ethyl-acetate fraction of ternary extracts from water:acetone:ethanol and methanol:acetone:ethanol against, respectively, VRE fm (MIC=19 µg/mL) and MRSA (MIC=39 µg/mL). On the other hand, moderate activity of the ethyl-acetate fractions from primary (except water), secondary and ternary extracts (MIC=625 µg/mL) was noted against KPC. The quadratic and special cubic models were significant for polyphenols and gallocatechin contents, respectively. Fit models to dry residue and epigallocatechin contents were not possible. PCA and HCA of the chromatographic fingerprints were disturbed by displacement retention time of some peaks, but the ultraviolet spectra indicated the homogeneous presence of flavan-3-ols characteristic of tannins. The MS confirmed the presence of gallic acid, gallocatechin, and epigallocatechin in extracts, and suggested the presence of monomers and dimers of B- and A-type prodelphinidins gallate, as well as a methyl gallate. Conclusion Our results showed the antibacterial potential of L . brasiliense extracts against multidrug–resistant Gram-positive bacteria, such as VRE fm and MRSA. The statistical design was a important tool to evaluate the biological activity by optimized form. The presence of some phenolic compounds was also demonstrated in extracts. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Among amphibians, 15 of the 47 species reported to be used in traditional medicines belong to the family Bufonidae, which demonstrates their potential in pharmacological and natural products research. For example, Asian and American tribes use the skin and the parotoid gland secretions of some common toads in the treatment of hemorrhages, bites and stings from venomous animals, skin and stomach disorders, as well as several types of cancers. Overarching objective In addition to reviewing the occurrence of chemical constituents present in the family Bufonidae, the cytotoxic and biomedical potential of the active compounds produced by different taxa are presented. Methodology Available information on bioactive compounds isolated from species of the family Bufonidae was obtained from ACS Publications, Google, Google Scholar, Pubmed, Sciendirect and Springer. Papers written in Chinese, English, German and Spanish were considered. Results Recent reports show more than 30% of amphibians are in decline and some of bufonid species are considered to be extinct. For centuries, bufonids have been used as traditional folk remedies to treat allergies, inflammation, cancer, infections and other ailments, highlighting their importance as a prolific source for novel drugs and therapies. Toxins and bioactive chemical constituents from skin and parotid gland secretions of bufonid species can be grouped in five families, the guanidine alkaloids isolated and characterized from Atelopus , the lipophilic alkaloids isolated from Melanophryniscus , the indole alkaloids and bufadienolides known to be synthesized by species of bufonids, and peptides and proteins isolated from the skin and gastrointestinal extracts of some common toads. Overall, the bioactive secretions of this family of anurans may have antimicrobial, protease inhibitor and anticancer properties, as well as being active at the neuromuscular level. Conclusion In this article, the traditional uses, toxicity and pharmacological potential of chemical compounds from bufonids have been summarized. In spite of being reported to be used to treat several diseases, neither extracts nor metabolites from bufonids have been tested in such illness like acne, osteoporosis, arthritis and other illnesses. However, the cytotoxicity of these metabolites needs to be evaluated on adequate animal models due to the limited conditions of in vitro assays. Novel qualitative and quantitative tools based on MS spectrometry and Nuclear Magnetic Resonance spectroscopy is now available to study the complex secretions of bufonids. [ABSTRACT FROM AUTHOR]