Non-random medicinal plants selection in the Kichwa community of the Ecuadorian Amazon Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): Daniela M. Robles Arias, Daniela Cevallos, Orou G. Gaoue, Maria G. Fadiman, Tobin Hindle Abstract The non-random selection of medicinal plants theory, which predicts taxonomical biases in ethnopharmacopeias, indirectly demonstrates that traditional medicinal systems are rational and based in part on the therapeutic efficacy of plants. This theory suggests that because members of a taxonomical group share similar characteristics, some groups will be over-utilized in pharmacopeias, while other groups bereft of therapeutic potential will be under-utilized medicinally. Empirical evidence fo this theory comes from studies that used data collected at the national level which may lead to the overestimation of medicinal plant list given that some parts of the country (e.g., protected areas) can be unavailable for medicinal plant collection. Similarly, because medicinal plant importance and knowledge can be gender-specific and depends on the degree of exposure of a community, failure to account for gender and community experience can limit our understanding of non-random selection of medicinal plants. In this study, we used the negative binomial model and an examination of studentized residuals to demonstrate that a Kichwa community in the Ecuadorian Amazon over-utilized different sets of medicinal plant families depending on the gender of the informants or the experience of the community. We showed that utilizing local data instead of nationwide data reveals new over-utilized families. Seven of the nine most over-utilized medicinal plant families we found were previously reported in different biogeographical regions. The other two families are novel reports. Overall, our study proposes a novel method to uncover the intracultural heterogeneity of traditional knowledge and people non-random selection of medicinal plants at the local level. Graphical abstract

Hypericum olympicum L. recovers DNA damage and prevents MMP–9 activation induced by UVB in human dermal fibroblasts Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): İnci Kurt-Celep, Engin Celep, Selin Akyüz, Yiğit İnan, Timur Hakan Barak, Galip Akaydın, Dilek Telci, Erdem Yesilada Abstract Ethnopharmacological relevance Hypericum olympicum L. (Hypericaceae) flowering aerial parts has been utilized in Turkish folk medicine as a remedy against inflamed skin problems. Aim of the study This study was designed to state the effect of H. olympicum on dermatological problems. For this purpose effect of the plant extract on the DNA strand break and matrix metalloproteinase (MMP)–9 activity of human dermal fibroblast (HDFs) cells irradiated with UVB as well as antioxidant activity potential were studied. Materials and methods The methanolic extract of Hypericum olympicum (HOM) was prepared by maceration at room temperature. DNA damage and increased MMP–9 activity in HDFs were induced by UVB irradiation. The cell viability was measured by water–soluble tetrazolium salt (WST)–1 assay. The effects on DNA strand break was investigated by single gel electrophoresis (commonly known as Comet assay), while MMP–9 activity was observed by gelatin zymography assay. In vitro antioxidant tests were performed to indicate the effect on reactive oxygen species (ROS). The major metabolites were identified and their concentrations were measured by high performance thin layer chromatography (HPTLC). Results HOM was found to recover DNA damage dose–dependently. The enzymatic activity of MMP–9 was inhibited almost 100% by the treatment of 1.5 mg/mL of the extract. It also enhanced cell proliferation in those cells, and also it was shown to possess antioxidant activity. The major metabolites of HOM were identified as chlorogenic acid and quercetin glycosides (rutin, hyperoside, isoquercitrin). Conclusion Experimental studies have proven the traditional use of Hypericum olympicum in inflamed skin problems acting by inhibition of the inflammatory pathway and recovery of DNA damage induced experimentally. Graphical abstract

Ethnoveterinary knowledge of farmers in bilingual regions of Switzerland – is there potential to extend veterinary options to reduce antimicrobial use? Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): Doréane Mertenat, Maja Dal Cero, Christan R. Vogl, Silvia Ivemeyer, Beat Meier, Ariane Maeschli, Matthias Hamburger, Michael Walkenhorst Abstract Ethnopharmacological relevance In the pre-antibiotic era, a broad spectrum of medicinal plants was used to treat livestock. This knowledge was neglected in European veterinary medicine for decades but kept alive by farmers. Emergence of multidrug resistant bacterial strains requires a severely restricted use of antibiotics in veterinary medicine. We conducted a survey on the ethnoveterinary knowledge of farmers in the bilingual (French and German speaking) Western region of Switzerland, namely the cantons of Fribourg, Neuchâtel and Jura, and in the French speaking part of the canton of Bern. Aim of the study To find out whether differences exist in plants used by farmers in French speaking and bilingual regions of Switzerland as compared to our earlier studies conducted in Switzerland. Additional focus was on plants that are used in diseases which commonly are treated with antimicrobials, on plants used in skin afflictions, and on plants used in animal species such as horses, for which the range of veterinary medicinal products is limited. Material and methods We conducted in 2015 semistructured interviews with 62 dialog partners, mainly cattle keeping farmers but also 18 horse keeping farmers. Of these, 41 were native French (FNS) and 21 native German speakers (GNS). Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers satisfaction) were collected. Results A total of 345 homemade remedies were reported, of which 240 contained only one plant species (Homemade Single Species Herbal Remedy Reports; HSHR). A total of 289 use reports (UR) were mentioned for the 240 HSHR, and they comprised 77 plant species belonging to 41 botanical families. Of these, 35 plant species were solely reported from FNS, 20 from GNS, and 22 from both. Taking into account earlier ethnoveterinary studies conducted in Switzerland only 10 (FNS) and 6 (GNS) plant species connected with 7% of FNS and GNS UR respectively were “unique” to the respective language group. The majority of the UR (219) was for treatment of cattle, while 38 UR were intended to treat horses. The most UR were for treatment of gastrointestinal and skin diseases. The most frequently mentioned plants were Linum usitatissimum L., Coffea L., Matricaria chamomilla L., Camellia sinensis (L.) Kuntze, and Quercus robur L. for gastrointestinal diseases, and Calendula officinalis L., Hypericum perforatum L. and Sanicula europaea L. for skin afflictions. Conclusion No clear differences were found between the medicinal plants used by French native speakers and German native speakers. Several of the reported plants seem to be justified to widen the spectrum of veterinary therapeutic options in gastrointestinal and dermatological disorders in cattle and horses, and to reduce, at least to a certain degree, the need for antibiotic treatments. Our findings may help to strengthen the role of medicinal plants in veterinary research and practice, and to consider them as a further measure in official strategies for lowering the use of antibiotics. Graphical abstract

Paeonia lactiflora root extract suppresses cancer cachexia by down-regulating muscular NF-κB signalling and muscle-specific E3 ubiquitin ligases in cancer-bearing mice Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): Taehyun Bae, Jaewoong Jang, Hyunji Lee, Jaewon Song, Seyeon Chae, Minwoo Park, Chang-Gue Son, Seokmin Yoon, Yoosik Yoon Abstract Ethnopharmacological relevance The dried root of Paeonia lactiflora Pall. (Radix Paeoniae) has been traditionally used to treat various inflammatory diseases in many Asian countries. Aim of the study Cancer cachexia is a catabolic syndrome driven by inflammation and characterised by a loss of skeletal muscle. This study aimed to assess the effects of an ethanolic extract of Radix Paeoniae (RP) on cancer cachexia and elucidate its mechanism of action. Material and methods The anti-cachexic effect and mechanism of RP were examined in mouse models of cancer cachexia established in C57BL/6 mice by subcutaneously injecting Lewis lung carcinoma or MC38 colon carcinoma cells. Skeletal muscle tissues were analysed by RNAseq, real-time quantitative reverse transcription PCR, western blotting, and immunofluorescence microscopy. Megestrol acetate, which is recommended for the treatment of cachexia in cancer patients, was used as the comparator treatment in this study. Results In lung and colon cancer-bearing mice, RP significantly restored food intake and muscle mass, along with muscle function measured by grip strength and treadmill running time. In the skeletal muscle tissue of the cancer-bearing mice, RP suppressed NF-κB signalling and reduced inflammatory cytokines, including TNF-α, IL-6, and IL-1β; it also down-regulated the muscle-specific E3 ubiquitin ligases MuRF1 and MAFbx. Conclusion RP restored skeletal muscle function and mass in cancer-bearing mice by down-regulating the muscular NF-κB signalling pathway and muscle-specific E3 ubiquitin ligases. Our study indicates that RP is a potential candidate for development as a therapeutic agent against cancer cachexia. Graphical abstract

Antihypertensive and antidiabetic activities of Erythrina senegalensis DC (Fabaceae) stem bark aqueous extract on diabetic hypertensive rats Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): Danielle Claude Bilanda, Ronald à Goufani Bidingha, Paul Désiré Djomeni Dzeufiet, Yannick Bekono Fouda, Rodrigue Fifen Ngapout, Yannick Tcheutchoua, Pascal Emmanuel Owona, Steven Collins Njonte Wouamba, Lucie Tanfack Tatchou, Théophile Dimo, Pierre Kamtchouing Abstract Ethnopharmacological relevance Erythrina senegalensis is traditionally used in Cameroon for its relaxing and hypoglycemic properties in the treatment of cardiovascular diseases and diabetes. Aim of the study High blood pressure and diabetes mellitus are frequently linked. These pathologies represent major risk factors for cardiovascular and renal diseases. The present study was designed to evaluate the antidiabetic and antihypertensive activity of the stem bark of Erythrina senegalensis aqueous extract in male hypertensive diabetic rats (HDR). Materials and methods Hypertension and diabetes were induced by oral administration of sucrose (15%) and ethanol (40°) at doses of 1.5 g/kg and 5 g/kg respectively for 30 days, followed by an intravenous injection of streptozotocin (STZ; 40 mg/kg). A control group of 5 rats received distilled water (10 mL/kg) followed by intravenous injection of 0.9% NaCl (1 mL/100 g). HDR were divided into 4 groups of 5 rats each according to their blood glucose level and continued to receive ethanol in association with: distilled water (10 mL/kg); group I, metformin (200 mg/kg)+nifedipine (10 mg/kg); group II, plant extract (100 and 200 mg/kg) group IV and V, respectively for 28 days. At the end of the treatment, hemodynamic parameters were recorded by the direct method. Animals were sacrificed; blood and organs (aorta, heart, liver, and kidneys) were collected for biochemical and histological analysis. Phytochemistry and HPLC–DAD–HRESI-MS were used to determine the major compounds of the extract. Results The administration of sucrose, alcohol, and STZ resulted in a significant increase in blood glucose, hemodynamic parameters, and body weight loss. A significant decrease in pancreatic islets size, nitrite, GSH, SOD and catalase activity was observed in HDR. There was also a significant increase in serum triglycerides, total cholesterol, creatinine, bilirubin, and transaminases activity in HDR. The aqueous extract of E. senegalensis, as well as the metformin + nifedipine combination, significantly improved all these parameters. HPLC coupled to both diode array and mass spectrometry detectors revealed the presence of 15 compounds and 11 of them were identified. Conclusion These results suggest that the aqueous extract of E. senegalensis possess antihypertensive, hypoglycemic, hypolipidemic, cardiomodulator and antioxidant properties involved in the improvement of the metabolic disorders found in HDR. This may be due at least in part to the presence of Erysenegalensein (D, O, N, E), Warangalone, senegalensin and 6,8-diprenylgenistein identified in the extract. Graphical abstract

A network pharmacology approach to discover action mechanisms of Yangxinshi Tablet for improving energy metabolism in chronic ischemic heart failure Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): Ruo-ming Wu, Bing Jiang, Hui Li, Wen-Zhen Dang, Wei-Lian Bao, Hai-Dong Li, Guan Ye, Xiaoyan Shen Abstract Ethnopharmacological relevance Most cardiovascular diseases ultimately result in heart failure, an intractable problem in modern medicine. Yangxinshi tablet (YXS) is a Chinese medicine formula that is used clinically to treat coronary heart disease. However, the active compounds, potential targets, and pharmacological and molecular mechanism of its anti-heart failure activity remain unclear. Therefore, further investigation is required. Aim of study Active ingredients and potential targets of YXS for treating heart failure have been reported previously. However, the molecular functions or biological processes of YXS in energy metabolism have not been discovered. To date, no experimental study to validate the potential anti-heart failure mechanism of YXS. The aim of this study was to study the therapeutic effect of YXS on rats with chronic ischemic heart failure by evaluating rat cardiac function and exercise tolerance, and to explore its potential mechanism by network pharmacology, western blotting, quantitative RT-PCR and histological analysis. Materials and methods In this investigation, chronic ischemic heart failure rats were randomly assigned to five groups: control group (sham operation), model group (0.5% CMC-Na), trimetazidine group (positive control) and two YXS groups (low- and high-dose groups). Experimental rats were treated by gavage with 10 mg/kg/d (clinical equivalent dose) trimetazidine (TMZ), 500 mg/kg/d (clinical equivalent dose) YXS and 1000 mg/kg/d YXS, respectively, for 5 weeks. The cardiac functions of rats were detected by High-Resolution In Vivo Imaging System. We elucidated novel understanding of the active compounds of YXS in rat plasma and predicted the energy metabolism related targets and processes for heart failure. Then, we validated experimentally the targets and mechanism of YXS on these pathological processes in vivo. Results It was found that YXS was able to effectively improve cardiac LVIDs, LVEDV, LVESV and EF, decrease myocardial oxygen consumption and reduce myocardial infarct size in rats with chronic ischemic heart failure was similar to that of TMZ. We identified 63 major candidate targets for YXS that are closely to heart failure progression. Enrichment analysis revealed key targets for YXS associated to oxygen delivery, glucose utilization, and mitochondrial biogenesis. Meanwhile, we validated that YXS could promote the expression of downstream HIF-1α, PGC1α and GLUT4 by increasing phosphorylation of PI3K, Akt, mTOR, rpS6 and AMPK. The results show that YXS could activate related PI3K/Akt/mTOR/rpS6/HIF-1α and AMPK/PGC1α/GLUT4 signaling pathways in chronic ischemic heart failure rats. Further experiments demonstrated that YXS increased mitochondrial biogenesis in chronic ischemic heart failure rats and improved exercise tolerance Conclusion YXS treated chronic ischemic heart failure through activating its targets which play pivotal roles in oxygen delivery, glucose utilization and mitochondrial biogenesis to improve energy metabolism through a multi-component, multi-level, multi-target, multi-pathway and multi-mechanism approaches. Graphical abstract

In vitro differentiation induction of embryonal carcinoma stem cells into insulin-producing cells by Cichorium intybus L. leaf extract Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): M. Ebrahiminia, F. Esmaeili, L. Shabani Abstract Ethnopharmacological relevance Medicinal herb Cichorium intybus L. (chicory) has been used traditionally for the treatment of various diseases, including diabetes. One of the promising therapeutic options to treat diabetes is replacing the degenerative pancreatic β cells by stem cell-derived IPCs (insulin-producing cells). Aim of the study By the combination of cell therapy as a modern approach and traditional medicine, the current study was designed to evaluate the effects of chicory leaf extract (LE) on the differentiation potential of P19 EC cells (an embryonal carcinoma stem cell line) into IPCs. Materials and methods The plant (voucher no. 4567) were collected and deposited in the herbarium of Shahrekord University. In vitro experiments were designed to compare the effects of various concentrations of LE on the differentiation potential of P19 EC cells. Results The differentiated cells showed morphological characteristics of pancreatic β cells. They could also synthesized and secreted insulin when exposed to glucose. Moreover, the cells expressed specific proteins and genes of mature pancreatic β cells. Conclusions In conclusion, LE as a natural herbal extract was efficiently able to induce the differentiation of P19 EC cells into the clusters similar to pancreatic islets with the molecular, cellular and functional characteristics of mature β cells. Graphical abstract

Improvement in mitochondrial function underlies the effects of ANNAO tablets on attenuating cerebral ischemia-reperfusion injuries Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): Yi Zhang, Mingyue Cao, Youming Wu, Jun Wang, Ji Zheng, Nasi Liu, Nan Yang, Yanyong Liu Abstract Ethnopharmacological relevance ANNAO tablets derive from Chinese classical prescriptions of Angong Niuhuang Pills with modified compositions, which have been singly or combined used for stoke associated neurological disorders. However the underlying mechanism is not yet well-defined, the present study investigated its anti-ischemic effects in rat middle cerebral artery occlusion (MCAO) model and focused on mitochondrial quality control. Materials and methods Rats were subjected to 2 h of brain ischemia followed by 1 day or up to 7 days of reperfusion. Vehicle, ANNAO tablets or Edaravone were given at 1h after the start of reperfusion for 1 day or successive 7 days in MCAO rats. For the behavior assessment, Longa test and modified Neurological Severity Scores (m NSS) test were performed. Following the behavioral assessment, we assessed the protein expressions related to mitochondrial function. Moreover, we also assessed the neuroprotective effects of ANNAO tablets by immunohistochemical analysis. Results Compared with sham rats, ANNAO tablets improved the behavioral performance and decreased the infarction volume in the MCAO rats. Western blotting results showed that ANNAO tablets altered the expression level of multiple proteins related to mitochondrial function, elevated the ratio of Bcl-2/Bax and inhibited the apoptosis. Additionally, ANNAO tablets increased the number of NeuN positive neurons. Conclusions The obtained data demonstrated that ANNAO tablets exhibited an obvious anti-cerebral ischemia-reperfusion effect, which could be attributed to the improvement of mitochondrial quality control. Graphical abstract

Dezhou donkey (Equus asinus) milk a potential treatment strategy for type 2 diabetes Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): Yan Li, Yumei Fan, Abdul Sami Shaikh, Zhendong Wang, Dongliang Wang, Haining Tan Abstract Ethnopharmacological relevance Donkey (Equus asinus) milk has become a medical and nutrient product since ancient times. In addition, donkey milk was regarded as a medicinal food and substitute product for infant formula in some ancient western countries. Chinese ancient medical books documented the medicinal value of donkey milk, using donkey milk to treat diabetes, cough and jaundice. Aim of the study To investigate the donkey milk’s components and anti-diabetic effect of donkey milk in vitro and in vivo and to study the molecular mechanism of donkey milk was an anti-diabetic medication. Materials and methods In this study, the gastrointestinal digested donkey milk was simulated in vitro and its products of protein digestion were analyzed by SDS-PAGE. We then performed cell viability assay, insulin secretion assay, animal experiments and ELISA assays to study the anti-diabetic effect of donkey milk in vitro and in vivo. Donkey milk’s anti-diabetic molecular mechanism and specific targets were detected by using quantitative real time PCR. Results Lysozyme (LZ) and α-lactalbumin (α-La) exhibited significantly lower digestibility and higher retention than the other components of donkey milk. In vitro, 500 μg/mL of donkey milk could improve damaged β-cells viability significantly (P < 0.0001). In vivo, the blood glucose and HOMA-IR of diabetic rats treated with donkey milk were 14.23 ± 5.18 mM and 74.94 ± 23.62, respectively, whereas the diabetic group were 22.18 ± 2.23 mM and 112.16 ± 18.44, respectively (P < 0.01). The SOD value of donkey milk group was 265.87 ± 21.29 U/L, while the SOD value of diabetic group was 193.20 ± 52.07 U/L (P < 0.05). These results indicated that the blood glucose was reduced, the ability of the body to eliminate free radicals was enhanced, antioxidant levels in the body was increased, insulin resistance was improved in type 2 diabetic rats after donkey milk powder fed for 4 weeks. Furthermore, donkey milk could treat diabetes through down-regulating phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6PC). Conclusions Donkey milk has played an important role in the treatment of type 2 diabetes, and contributed to the development of the donkey milk products. Graphical abstract

Melissa officinalis ssp. altissima extracts: A therapeutic approach targeting psoriasis in mice Publication date: 10 January 2020 Source: Journal of Ethnopharmacology, Volume 246 Author(s): Dimas Dimitris, Tomou Ekaterina-Michaela, Karamani Christina, Sfiniadakis Ioannis, Siakavella K. Ioanna, Liakopoulou Aggeliki, Hatziantoniou Sophia, Rallis Michael, Skaltsa Helen Abstract Ethnopharmacological relevance Melissa officinalis L., commonly known as lemon balm, is one of the most well known edible and medicinal plants of the Lamiaceae family. It is quoted in almost all known medical treatises, from Antiquity up to modern era, such as Corpus Hippocraticum, Dioscorides’ De Materia Medica and later on in medieval medical manuscripts and Pharmacopoeias. Actually, it is widely used as herbal medicine for the relief of mild symptoms of mental stress, to aid sleep and for symptomatic treatment of mild gastrointestinal complaints including bloating and flatulence. In Greece, the empirical physicians “vikoyiatroi” recommended the decoction of dry flowers and leaves to treat tracheobronchitis, hysteria, epilepsy, heart arrhythmias, as hypnotic and against skin disorders. Aim of the study The present study was conducted to investigate the potential beneficial effects in psoriasis in mice of M. officinalis ssp. altissima and to carry out the chemical analysis in order to reveal its main bioactive secondary metabolites. Materials and methods Non polar and polar extracts of M. officinalis ssp. altissima aerial parts were prepared by using dichloromethane and methanol, successively; in addition a decoction was made upon oral information by local users in Crete, where the plant was collected. All three preparations were chemically analyzed in order to isolate their main constituents. Chemical structures of all isolated compounds were determined by 1D, 2D-NMR and UV–Vis spectroscopy. Furthermore, the antioxidant potential of extracts and decoction was evaluated through DPPH radical scavenging capability. The in vivo in mice anti-psoriatic efficacy of all preparations was estimated through clinical and histopathological assessment and measurements of TEWL and hydration. Results The dichloromethane extract yielded ursolic acid, 2α-hydroxy-ursolic acid, pomolic acid, 3β-stearyloxy-urs-12-ene, oleanolic acid, noropacursane and campesterol; the methanol extract afforded rosmarinic acid and methyl rosmarinate, while from the decoction caffeic acid, 3-(3,4-dihydroxyphenyl)lactic acid and rosmarinic acid were isolated. The psoriasis evaluation, based on PASI score, photodocumentation and histopathological estimation showed that the decoction primarily and the dichloromethane extract secondly could significantly contribute to psoriasis treatment. The decoction seems able to reestablish skin physiology by decreasing dryness and enhancing skin barrier function. Moreover, the decoction showed the best antioxidant activity, while the dichloromethane extract the weakest. Conclusions The triterpene derivatives of the dichloromethane extract are likely to be responsible for its anti-psoriatic activity. The abundant polyphenolic load of the decoction contributes to its high antioxidant activity and the most effective results against psoriasis. The anti-psoriatic activity of the decoction confirmed the traditional use of this plant as antioxidant, wound healing and skin barrier repair agent. Graphical abstract