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Background The aim of the present study was to investigate the antidiarrheal effect of Berberis heteropoda Schrenk roots (BHS), which are used by Chinese minorities to treat diarrhea, through regulation of intestinal flora and related signaling pathways. Methods Wistar rats were randomly divided into 6 groups: Control group (Con), Model group (Mod), three BHS groups (BHS-L (0.65 g/kg), BHS-M (1.955 g/kg), BHS-H (5.86 g/kg) and Bifidobacterium group (Bif). The model of diarrhea-based irritable bowel syndrome (D-IBS) was induced by intragastric administration combined with restraint stress. The CRD method was used to determine the AWR score and the Bristol fecal score. Quantification of the intestinal bacteria groups in feces was performed using colony counting on plates. The mRNA expression levels of Gpr41, Gpr43, TLR2, TLR4, and nuclear protein κB were determined by qRT-PCR, and the relative abundances of intestinal flora in the intestinal contents were determined by high-throughput gene sequencing ratios. Results Oral administration of BHS (L, M and H) significantly reduced the AWR score and the Bristol fecal score, significantly relieved diarrhea in D-IBS rats, reduced the number of Enterococci and Enterobacteria in feces, increased the number of Bifidobacteria and Lactobacilli, and upregulated the expression of SCFA in plasma. qRT-PCR analysis showed that the expression of TLR2, TLR4, Gpr41, Gpr43 and NF-κB in the BHS groups was downregulated. D-IBS rats reduced the abundance and diversity of intestinal flora and BHS (L, M and H) regulated the abundance and diversity of their intestinal flora. Conclusion The above data suggest that BHS potentially alleviates diarrhea, intestinal flora disorder and intestinal inflammation in D-IBS rats by regulating the immunological pathways. BHS is a promising agent in the treatment of D-IBS.

Berberis integerrima commonly known as "barberry" belongs to the Berberidaceae family and has been used as a medicinal plant in Iranian traditional medicine.Our aim in this study was to investigate the effects of barberry consumption on blood pressure (BP).Eighty-four medicated hypertensive patients were selected and randomly allocated to barberry and placebo groups. The barberry group received 10 g/day dried purple-black barberry powder, once daily, for 2-months. Systolic, diastolic, and mean arterial BP was assessed through 24-h ambulatory BP monitoring before and after 2-month treatment. The estimation of sodium and potassium intake was done through measurement of sodium and potassium in 24-h urinary samples. Plasma and urinary nitrite, and nitrate (NOx) levels, as well as plasma angiotensin-converting enzyme (ACE) activity, were also determined.Seventy-eight participants with an average age of 54.12 ± 10.32 years and BMI of 27.93 ± 2.22 kg/mIn patients treated with antihypertensive drugs, daily consumption of purple-black barberry can be effective in improving systolic BP control.

ABSTRCT Ethnopharmacological relevance Berberis dictyophylla F., a famous Tibetan medicine, has been used to prevent and treat diabetic retinopathy (DR) for thousands of years in clinic. However, its underlying mechanisms remain unclear. Aim of the study The present study was designed to probe the synergistic protection and involved mechanisms of berberine, magnoflorine and berbamine from Berberis dictyophylla F. on the spontaneous retinal damage of db/db mice. Materials and methods The 14-week spontaneous model of DR in db/db mice were randomly divided into eight groups: model group, calcium dobesilate (CaDob, 0.23 g/kg) group and groups 1–6 (different proportional three active ingredients from Berberis dictyophylla F.). All mice were intragastrically administrated for a continuous 12 weeks. Body weight and fasting blood glucose (FBG) were recorded and measured. Hematoxylin-eosin and periodic acid–Schiff (PAS) stainings were employed to evaluate the pathological changes and abnormal angiogenesis of the retina. ELISA was performed to assess the levels of IL-6, HIF-1α and VEGF in the serum. Immunofluorescent staining was applied to detect the protein levels of CD31, VEGF, p-p38, p-JNK, p-ERK and NF-κB in retina. In addition, mRNA expression levels of VEGF, Bax and Bcl-2 in the retina were monitored by qRT-PCR analysis. Results Treatment with different proportional three active ingredients exerted no significant effect on the weight, but decreased the FBG, increased the number of retinal ganglionic cells and restored internal limiting membrane. The results of PAS staining demonstrated that the drug treatment decreased the ratio of endothelial cells to pericytes while thinned the basal membrane of retinal vessels. Moreover, these different proportional active ingredients can markedly downregulate the protein levels of retinal CD31 and VEGF, and serum HIF-1α and VEGF. The gene expression of retinal VEGF was also suppressed. The levels of retinal p-p38, p-JNK and p-ERK proteins were decreased by drug treatment. Finally, drug treatment reversed the proinflammatory factors of retinal NF-κB and serum IL-6, and proapoptotic Bax gene expression, while increased antiapoptotic Bcl-2 gene expression. Conclusions These results indicated that DR in db/db mice can be ameliorated by treatment with different proportional three active ingredients from Berberis dictyophylla F. The potential vascular protection mechanisms may be involved in inhibiting the phosphorylation of the MAPK signaling pathway, thus decreasing inflammatory and apoptotic events.

Ethnopharmacological relevance: Patagonia is the southernmost part of the South American continent including Chile and Argentina. Berries and wild fruits have been gathered by the native Patagonians as food and medicine for over 14,000 years. The economic potential of the native berries as health promoting and relevant sources of bioactive substances has become apparent with several studies in the last decades. Aim of study: This work aims to provide an insight into the ethnohistorical records of wild edible fruits from Patagonia starting with the archeobotanical studies to the contemporary use of the resources. The chemical and bioactivity studies on the native fruits are presented and discussed. Methodology: A search of electronic databases including Scopus, Scielo, Google Scholar, PubMed, ScienceDirect and SciFinder, as well as hand-search was carried out to perform an integrative review on the native Patagonian berries. Results: The use of native berries as food and medicine by the ancient hunter-gatherer societies can be traced back to the early occupation of Patagonia. The same species used in prehistoric times are still used as food by the contemporary population in this area. Chemical and bioactivity studies have reported remarkable activities in several of the native berries, including calafate (Berberis spp.), native strawberry (Fragaria chiloensis), currants (Ribes spp.), Patagonian raspberries (Rubus spp.) and maqui (Aristotelia chilensis) fruits. The increasing demand for maqui and calafate led to the selection of varieties for commercial production. The fruit constituents show strong antioxidant and inhibitory effect towards enzymes associated with metabolic syndrome, including α-amylase, α-glucosidase and lipase. Some berry constituents exert anti-inflammatory effects in vitro. The phytochemicals identified include a wide array of phenolics of different structural skeletons. Changes in composition and bioactivity after simulated gastric and intestinal digestion, as well as colonic fermentation, have been reported in some Patagonian species. Conclusions: Patagonian berries are a relevant source of bioactive compounds with several health promoting properties. The long tradition of use and the interest of the population for their consumption has led to the development of some of this fruits as new potential crops. The ethnobotanical evidence shows a shared knowledge among the different indigenous communities on plant uses according to the local resources, and an integration of the ancient knowledge into the contemporary society. Other species are being investigated to get a more complete picture of the food and medicinal plants from Patagonia. Fil: Schmeda Hirschmann, Guillermo. Universidad de Talca; Chile Fil: Jiménez Aspee, Felipe. Universidad de Talca; Chile Fil: Theoduloz, Cristina. Universidad de Talca; Chile Fil: Ladio, Ana Haydee. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Laboratorio de Ecotono; Argentina

Background The stem bark of Berberis kansuensis Schneid (BK) is a commonly used Tibetan medicine for the treatment of type 2 diabetes (T2D). However, its therapeutic mechanisms remain unclear. Aim of the study Our aim is to clarify the role of gut microbiota in the anti-diabetic activity of BK extract. Materials and methods High fat diet combined with low-dose streptozotocin (45 mg/kg) was used to establish a T2D rat model, and the body weight of rats was measured every five days. Fasting blood glucose (FBG), glycosylated serum protein (GSP), insulin resistance index (HOMA-IR), insulin sensitivity index (ISI), lipopolysaccharide (LPS), and three inflammatory factors (TNF-α, IL-1 β and IL-6) were measured to evaluate the anti-diabetic activity of BK. Moreover, pseudo-germ-free animals were prepared by oral administration of an antibiotic mixture (100 mg/kg neomycin, 100 mg/kg ampicillin and 50 mg/kg metronidazole) twice per day for 6 days to assess the role of gut microbiota. Gut microbiota analysis was performed through 16S rRNA high-throughput sequencing method. Results After 30 days of administration, BK extract could significantly decrease the levels of body weight, FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1β and IL-6, and increase ISI levels in T2D rats. However, when the gut microbiota of T2D rats was disturbed by antibiotics, BK could not improve HOMA-IR and ISI levels in T2D rats. The results indicated that the anti-diabetic effect of BK might depend on the gut microbiota. Moreover, sequencing of 16S rRNA genes demonstrated that BK could significantly improve the gut microbiota disorder of T2D rats. Specifically, BK increased the abundance of phyla Bacteroidetes and genera Akkermansia and the ratio of Bacteroides/Firmicutes, while reducing the abundance of phyla Proteobacteria and genera Collinella, [Ruminococcus]_gauvreauii_Group, Escherichia Shigella, Enterococcus, Fusobacterium, Holdemanella, and Prevotella_9 in T2D rats. Additionally, correlation analysis revealed that Akkermansia was positively correlated with ISI, while [Ruminococcus]_gauvreauii_Group, Collinella, Escherichia Shigella, Enterococcus, Fusobacterium, Holdemanella and Prevotella_9 were positively correlated with FBG, GSP, LPS, HOMA-IR, TNF-α, IL-1β, and IL-6. Conclusion BK extract has a good anti-diabetic effect on T2D rats. The mechanism by which this extract exerts its action is, at least partly, related to its regulation of gut microbiota.

Ethnopharmacological relevance “Zereshk-e-Saghir” (ZES), one of the traditional herbal medicines in old manuscripts of Persian hakims, has been used for the treatment of liver disorders. This current study is aimed to evaluate ZES effects on animal model to investigate its safety and hepatoprotective activity. Materials and methods ZES was prepared according to a traditional method by blending aqueous extracts of Berberis vulgaris L., with fine particles of other plants including Rosa damascene Mill, Cichorium intybus L., Cucumis sativus L., Portulaca oleracea L., Rheum palmatum L., and Nardostachys jatamansi DC.. The lethality of ZES was determined in male NMRI mice. Acute organ toxicity of ZES (750 and 1500 mg/kg for 15 days, orally) was evaluated by measuring the cell blood count, liver marker enzymes, creatinine, antioxidant status and histopathological examinations in rats. CCl4-induced liver toxicity was used to examine the hepatoprotective effects of the preparation. The rats were pretreated with 250, 500, 750 and 1500 mg/kg ZES by gavage for 15 days. At day 16, the rats were intraperitoneally injected 1 ml/kg CCl4 in olive oil. Forty-eight hours after CCl4 injection, the animals were sacrificed and their liver samples and blood were collected for determination of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase (ALT, AST, and ALP), histopathological examinations and antioxidant status. Results Treatment of the mice with a single dose of ZES up to 2 g/kg did not cause mortality. Treatment of the rats with doses of 750 and 1500 mg/kg for 15 days showed no significant hematotoxicity and hepatotoxicity. Treatment of the rats with ZES reduced the increased serum levels of ALT, AST, and ALP induced by CCl4 at the doses of 250, 500, and 750 mg/kg. This was almost confirmed by histopathological examinations. Pretreatment with ZES also decreased lipid peroxidation and maintained the levels of glutathione and total antioxidant capacity. Conclusions The present in vivo study revealed that the long term usage of ZES was safe for organs in laboratory animals. Meanwhile, prescribing the traditionally-recommended dose of ZES can be probably used against the liver injuries induced by xenobiotics. Further studies in other models of liver injuries are recommended for finding the exact hepatoprotective mechanism of ZES.

Ethnopharmacological relevance Berberis orthobotrys (BORM) is a medical plant with a long history in traditional usage for the treatment of wounds, cancer, gastrointestinal malady and several other diseases. Our previous studies identified the endemic Pakistani plant Berberis orthobotrys Bien. ex Aitch. as promising source for the treatment of breast cancer and osteosarcoma. Aim of the study The present study was aimed to evaluate the anti-cancer properties of 26 plant derived extracts and compounds including the methanolic root extract of Berberis orthobotrys (BORM) on pediatric alveolar rhabdomyosarcoma (RMA), which is known to develop drug resistance, metastatic invasion and potential tumor progression. Materials and methods The main anti-tumor activity of BORM was verified by focusing on morphological, cell structural and metabolic alterations via metabolic profiling, cell viability measurements, flow cytometry, western blotting and diverse microscopy-based methods using the human RMA cell line Rh30. Results Exposure of 25 µg/ml BORM exerts an influence on the cell stability, the degradation of oncosomes as well as the shutdown of the metabolic activity of RMA cells, primarily by downregulation of the energy metabolism. Therefore glycyl-aspartic acid and N-acetyl serine decreased moderately, and uracil increased intracellularly. On healthy, non-transformed muscle cells BORM revealed very low metabolic alterations and nearly no cytotoxic impact. Furthermore, BORM is also capable to reduce Rh30 cell migration (~50%) and proliferation (induced G2/M cycle arrest) as well as to initiate apoptosis confirmed by reduced Bcl-2, Bax and PCNA expression and induced PARP-1 cleavage. Conclusions The study provides the first evidence, that BORM treatment is effective against RMA cells with low side effects on healthy cells.

Ethnopharmacological relevance The highlands of Northern Balochistan are the hot spots of medicinal and endemic plant in Pakistan. These plants are still commonly used for medicinal purposes by local people in their daily lives. This study first documented the information about the medicinal uses of endemic species of Balochistan-province Pakistan. Materials and methods A survey was performed using open ended questionnaires, free listening and personal observations with 152 informants (54% female, 46% male). In addition, the use value (MUV), use report (UR), fidelity level (FL), frequency citation (FC), relative frequency citation (RFC), family importance value (FIV) of species were determined and the informant consensus factor (ICF) was calculated for the medicinal plants included in the study. Results A total of 24 endemic plants belonging to 19 genera and 14 families were used by the local inhabitants to treat 12 categories of various diseases. The most common families of endemic plant species as depicted by its number of species (6 species) and FIV (9.9) was Fabaceae as the dominant family. The endemic plant species comprised perennial herbs (30%), annual herbs (25%), shrubs (29%) and under shrubs (16% each), no endemic tree species was reported in the study area. The highest number of species were used in the treatment of gastrointestinal diseases (12 species). The main route of administration is oral injection (62%) while the most frequently used form of external administration of herbal medicine was paste (5.4%) and the most commonly applied methods of preparation are powder (48.2%). Highest use report were calculated for Allium baluchistanicum and Viola makranica, (8 UR each), and least use report were calculated for two species Heliotropium remotiflorum and Tetracme stocksii (1 UR for each). Use values of the recorded plant species have been calculated which showed a highest use value of (0.73) for A. baluchistanicum and (0.56) for Berberis baluchistanica while the lowest UVs were attained for T. stocksii (0.13). Highest RFC value were calculated for Achillea millefolium (0.19) and least RFC were calculated for Blepharis sindica (0.02). The endemic species with 100% fidelity level was calculated for two plant species i.e. Seriphidium quettense and B. baluchistanica. Conclusions The Balochistan is rich in endemic and other medicinal plants, still needs more exploration and study. Thus, it is important to document and reconstitute the remainders of the ancient medical practices which exist in Balochistan and other areas of the world, and preserve this knowledge for future generations. The endemic species which are used in traditional medicine in the region lacks phototherapeutic evidence. It is necessary to perform phytochemical or pharmacological studies to explore the potential of plants used for medicinal purposes. Overgrazing, urbanization and unsustainable harvesting of such rare and endemic medicinal plants in this region is facing severe threats of extinction. It is thus recommended that cultivation techniques be formulated, especially for the most important endemic plant medicinal species of the region.

Ethnopharmacological relevance The aim of this study was to document the medicinal uses of plants in district Mastung of Balochistan province, Pakistan. The ethnobotanical results contain quantitative information on medicinal plants diversity documented for the first time in the area. Materials and methods The information was collected through semi-structured interviews, rapid appraisal approach, open ended questionnaire and personal observations. Results were analyzed using quantitative indices of information consent factor (ICF), fidelity level (FL), use value (UV), frequency citation (FC) and relative frequency citation (RFC). Results In total of 102 plant species belonging to 47 families were reported for the medicinal purposes. Asteraceae was found to be dominant family in terms of species in the area with 11 species. The whole plant and leaves were noted as most frequently used parts (24%). Decoction (31% with 40 species) was the most commonly used preparation method. Highest ICF value (1) was recorded for antidote category. 100% fidelity level was found for four plant species i.e. Achillea welhemsii, Caralluma tuberculata , Citrullus colocynthis, and Seripidium quettense. The highest use value was reported for the Acroptilon repens (0.5) while highest RFC value was calculated for Berberis balochistanica and Citrullus colocynthis (0.18). Highest use report was calculated for Caralluma tuberculata , Citrullus colocynthis , Malva neglecta and Mentha longifolia with five use reports for each. Conclusions The area is rich in medicinal plants and these plants are still commonly used for medicinal purposes among the people in their daily lives. However, there is a gradual loss of traditional knowledge about these plants in new generation. This study provides basis for the conservation of the local flora, its use as food and medicine. It also provides various socio-economic dimensions associated with the common people.

Ethnopharmacological relevance Traditionally Berberis aristata is employed for its supposed properties in treatment of joint pain and also used in alleviating symptoms of menopause. Aim of the study The aim of the present study is to evaluate the antiosteoporotic effect of Berberis aristata in ovariectomized (OVX) rats. Materials and methods Sprague–Dawley rats were divided into sham and OVX groups. The OVX rats were further divided into four groups, which received standard estrogen (0.0563 mg/kg) and 100, 300, and 500 mg/kg aqueous-methanol extract of Berberis aristata, daily for 42 days. The uterine weight, bone loss, ash content, biomechanical, biochemical and histopathological observation were carried out for antiosteoporotic activity. Results The experimental animals treated with Berberis aristata aqueous-methanol extract showed dose dependent activity. The significant increase in uterine weight, femur BMD, ash content and lumbar hardness were observed. In addition, increased levels of calcium and phosphorus in serum and significant decreased in urine were observed as compared to control OVX group. The histopathological results also confirm the protective effect of extract. Conclusion The present findings strongly suggest that Berberis aristata possess the potent antiosteoporosis activity in ovariectomized rats and substantiates the ethnic use in treatment of postmenopausal osteoporosis.

Aim of the study The present investigation is an attempt to find out ethnopharmacological application of medicinal plants to cure skin diseases and in folk cosmetics. Method We interviewed respondents in 30 remote sites of North-West Frontier Province by a structured interview form in the local language and respondents were queried for the type of herbal cure known to him. Results A total of 66 plant species belonging to 45 families have been recorded. Seventy-five medications for 15 skin diseases and cosmetics were documented. The mode of application was topical as well as oral administration. Water, milk, ghee, oil, eggs, sulphur and butter are used during administration of herbal remedies. About 15 plant species are known for their use to cure multiple skin diseases. Among these Berberis lyceum, Bergenia ciliata, Melia azedarach, Otostegia limbata, Phyla nodiflora, Prunus persica and Zingiber officinale constitutes major plants. The herbal cosmetics products range from face freshness, removal of ugly spots, hair care, and colouring of palm, feet, gums, and teeth. Conclusion Most of the reported species are wild and rare; this demands an urgent attention to conserve such vital resources so as to optimize their use in the primary health care system. Since most of the skin diseases are caused by bacteria, viruses and fungi in this context, phytochemical screening for active constituents, biological activities and clinical studies is of global importance.

Ethnopharmacological relevance Berberis aristata DC root is used in traditional medicine for a number of ailments including metabolic disorders. Aim of the study The aim of the present study was to explore the antihyperglycemic and antioxidant potential of 50% aqueous ethanolic root extract of Berberis aristata (BA) in alloxan induced diabetic rats. Materials and methods BA root extract (250 mg/kg) was administered to diabetic rats and standard drug glybenclamide (0.6 mg/kg) to group serving as positive control. Effect of extract on antioxidant and carbohydrate metabolism regulating enzymes of liver was studied in diabetic rats along with its safety parameters. Results The main constituents of root were identified as berberine, berbamine and palmatine through HPTLC. The extract besides being safe, lowered the blood glucose significantly without any hypoglycemic effect on their control counterparts. It increased CAT, SOD, GPx, GR activity significantly and reduced lipid peroxidation (41.6%) and protein carbonylation (30.15%). It also increased the glucokinase and glucose-6-phosphate dehydrogenase activities and decreased glucose-6-phosphatase activity in diabetic rats which play a critical role in glucose homeostasis. Conclusion Thus, the extract of Berberis sristata (root) has strong potential to regulate glucose homeostasis through decreased gluconeogenesis and oxidative stress.

Berberis vulgaris fruit (barberry) is known for its antiarrhythmic and sedative effects in Iranian traditional medicine. The effects of crude aqueous extract of barberry on rat arterial blood pressure and the contractile responses of isolated rat aortic rings and mesenteric bed to phenylephrine were investigated. We also examined effect of the extract on potassium currents recorded from cells in parabrachial nucleus and cerebellum rejoins of rat brain. Administration of the extract (0.05-1 mg/100 g body weight of rat) significantly reduced the mean arterial blood pressure and heart rate in anaesthetized normotensive and desoxycorticosteron acetate-induced hypertensive rats in a dose-dependent manner. Concentration-response curves for phenylephrine effects on isolated rat aortic rings and the isolated mesenteric beds in the presence of the extract were significantly shifted to the right. Application of the extract (1-50 microg/ml) shifted the activation threshold voltage to more negative potentials, leading to an enhancement in magnitude of the outward potassium current recorded from cells present in rat brain slices of parabrachial nucleus and cerebellum. This effect on potassium current may explain the sedative and neuroprotective effects of barberry. The present data support the hypothesis that the aqueous extract of barberry has beneficial effects on both cardiovascular and neural system suggesting a potential use for treatment of hypertension, tachycardia and some neuronal disorders, such as epilepsy and convulsion.