Berberis vulgaris L. extract supplementation exerts regulatory effects on the lifespan and healthspan of Drosophila through its antioxidant activity depending on the sex.

Worldwide the aging population continues to increase, so the concept of healthy longevity medicine has become increasingly significant in modern society. Berberis vulgaris L. fruits serve as a functional food supplement with a high concentration of bioactive compounds, which offer numerous health-promoting benefits. The goal of this study was to investigate the geroprotective effect of Berberis vulgaris L. extract. Here we show that extract of Berberis vulgaris L. can, depending on concentrate, increases lifespan up to 6%, promote healthspan (stress resistance up to 35%, locomotor activity up to 25%, integrity of the intestinal barrier up to 12%, metabolic rate up to 5%) of Drosophila melanogaster (in vitro) and exhibits antioxidant (using red blood cell tests) and antiglycation activity (using glycation of bovine serum albumin) (in vitro). In addition to this, the extract does not exhibit cytotoxic properties in vitro, unlike the well-known polyphenolic compound quercetin. qRT-PCR has revealed the involvement of metabolic, heat shock response and lipid metabolism genes in the observed effects.

Chitosan/alginate scaffold enhanced with Berberis vulgaris extract for osteocyte differentiation of ovine fetal stem cells.

Designing biocompatible polymers using plant derivatives can be extremely useful in tissue engineering, nanomedicine, and many other fields of medicine. In this study, it was first looked into how chitosan/alginate scaffolds were made and characterized in the presence of berberine and barberry fruit extract. Second, the process of proliferation and differentiation of ovine fetal BM-MSCs (bone marrow-mesenchymal stem cells) was assessed on these scaffolds after BM-MSCs were extracted and confirmed by developing into osteocyte and adipose cells. To investigate the differentiation, treatment groups include (1) ovine fetal BM-MSCs were plated in Dulbecco's modified eagle medium culture medium with high glucose containing 10% fetal bovine serum and antibiotics (negative control), (2) ovine fetal BM-MSCs were plated in osteogenic differentiation medium (positive control group), (3) positive control group + barberry fruit extract, (4) positive control group + berberine, (5) ovine fetal BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate scaffold (hydrogel group), (6) ovine fetal BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate/barberry fruit extract scaffold (hydrogel group containing barberry fruit extract), and (7) ovine fetal BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate/berberine scaffold (hydrogel group containing berberine). Alkaline phosphatase (ALP) enzyme concentrations, mineralization rate using a calcium kit, and mineralization measurement by alizarin staining quantification were all found after 21 days of culture. In addition, real-time quantitative reverse transcription polymerase chain reaction was used to assess the expression of the ALP, COL1A2, and Runx2 genes. Days 5 and 7 had the lowest water absorption by the hydrogel scaffold containing barberry extract, which was significant in comparison to other groups (p < .05). Among the hydrogel scaffolds under study, the one containing barberry extract exhibited the lowest tensile strength, and this difference was statistically significant (p < .05). The chitosan/alginate hydrogel has the highest tensile strength of all of them. In comparison to the control and other treatment groups, the inclusion of berberine in the chitosan/alginate hydrogel significantly increased the expression of the ALP, Runx2, and COL1A2 genes (p < .05). The osteocyte differentiation of mesenchymal stem cells in in vitro settings appears to have been enhanced by the inclusion of berberine in the chitosan/alginate scaffold.

Anti-inflammatory, antioxidant, and immunomodulatory effects of Berberis vulgaris and its constituent berberine, experimental and clinical, a review.

Berberis vulgaris (B. vulgaris or barberry) is a medicinal plant that has been used for various purposes in traditional medicine. Berberine is one of the main alkaloids isolated from B. vulgaris and other plants. Both B. vulgaris and berberine have shown anti-inflammatory, antioxidant, and immunomodulatory effects in different experimental models and clinical trials. This review aims to summarize the current evidence on the mechanisms and applications of B. vulgaris and berberine in modulating inflammation, oxidative stress, and immune responses. The literature search was performed using PubMed, Scopus, and Google Scholar databases until August 2023. The results indicated that B. vulgaris and berberine could inhibit the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), interleukin 6 (IL-6), and interleukin-17 (IL-17), and enhance the expression of anti-inflammatory cytokines, such as interleukin 10 (IL-10) and transforming growth factor-ß (TGF-ß), in various cell types and tissues. B. vulgaris and berberine can also scavenge free radicals, increase antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and reduce lipid peroxidation and DNA damage. B. vulgaris and berberine have been reported to exert beneficial effects in several inflammatory, oxidative, and immune-related diseases, such as diabetes, obesity, cardiovascular diseases, neurodegenerative diseases, autoimmune diseases, allergic diseases, and infections. However, more studies are needed to elucidate the optimal doses, safety profiles, and potential interactions of B. vulgaris and berberine with other drugs or natural compounds.

Berberis vulgaris L. Root Extract as a Multi-Target Chemopreventive Agent against Colon Cancer Causing Apoptosis in Human Colon Adenocarcinoma Cell Lines.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of the chemopreventive action of the plant's methanolic root extract (BVR) against colon cancer cells. Studies were conducted in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3, 46.1, and 50.2 µg/mL for the LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of the cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. Nuclear double staining revealed the great proapoptotic BVR properties in HT-29 cells and subtle effect in LS180 cells. RT-qPCR with the relative quantification method showed significant changes in the expression of genes related to apoptosis in both the LS180 and HT-29 cells. The genes BCL2L1 (126.86-421.43%), BCL2L2 (240-286.02%), CASP3 (177.19-247.83%), and CASP9 (157.99-243.75%) had a significantly elevated expression, while BCL2 (25-52.03%) had a reduced expression compared to the untreated control. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93 ± 0.01, 122.92 ± 0.01, and 220.29 ± 0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+, and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62.60 ± 0.87% of enzyme inhibition. The chemical composition of BVR was determined using a UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). The results are very promising and encourage the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer, and were widely discussed alongside data from the literature.

Antioxidant and Cytotoxic Properties of Berberis vulgaris (L.) Stem Bark Dry Extract.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigated B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq tannic acid/100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq chlorogenic acid/100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC-HRMS/MS) and HPLC, and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods. Our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and berberine-berberine sulfate hydrate (BS)-investigated on Daphnia sp. revealed significant BS toxicity after 24 h, while BVE revealed considerable toxicity after 48 h and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated in different tumor cell lines after 24 and 48 h of treatments. The MTS assay evidenced dose- and time-dependent antiproliferative activity, which was higher for BS than BVE. The strongest diminution of tumor cell viability was recorded in the breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported in the normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected Berberis Species.

Berberis species have a long history of use in traditional Chinese medicine, Ayurvedic medicine, and Western herbal medicine. The aim of this study was the quantification of the main isoquinoline alkaloids in extracts obtained from various Berberis species by HPLC, in vitro and in silico determination of anti-cholinesterase activity, and in vitro and in vivo investigations of the cytotoxic activity of the investigated plant extracts and alkaloid standards. In particular, Berberis species whose activity had not been previously investigated were selected for the study. In the most investigated Berberis extracts, a high content of berberine and palmatine was determined. Alkaloid standards and most of the investigated plant extracts exhibit significant anti-cholinesterase activity. Molecular docking results confirmed that both alkaloids are more favourable for forming complexes with acetylcholinesterase compared to butyrylcholinesterase. The kinetic results obtained by HPLC-DAD indicated that berberine noncompetitively inhibited acetylcholinesterase, while butyrylcholinesterase was inhibited in a mixed mode. In turn, palmatine exhibited a mixed inhibition of acetylcholinesterase. The cytotoxic activity of berberine and palmatine standards and plant extracts were investigated against the human melanoma cell line (A375). The highest cytotoxicity was determined for extract obtained from Berberis pruinosa cortex. The cytotoxic properties of the extract were also determined in the in vivo investigations using the Danio rerio larvae xenograft model. The obtained results confirmed a significant effect of the Berberis pruinosa cortex extract on the number of cancer cells in a living organism. Our results showed that extracts obtained from Berberis species, especially the Berberis pruinosa cortex extract, can be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of neurodegenerative diseases and human melanoma.

Novel Core-shell Bioceramic Silica-Berberis vulgaris: Synthesis and Characterization.

Enhancements in bioceramic mixtures represent a significant avenue for achieving superior mechanical and biological properties. Therefore, the present study aimed to extract active compounds from Berberis vulgaris stems and fruits collected from the Khorasan province, employing advanced analytical techniques such as GC-MS and FTIR to elucidate the composition of these extracts. The derived extracts were utilized to synthesize novel nanocomposites, denoted as SiO2-MPS-stem extract and SiO2-MPS-fruit extract. Comprehensive Characterization of these composites was conducted through SEM, EDX mapping, FTIR, and XRD analyses. The characterization measurements validated the successful coating of silica with the extracts, resulting in a core-shell nanostructure with particle sizes below 60 nm. These composites were incorporated into bioceramics for dental root fillings with an equal weight ratio. The bioceramic material was subjected to the same aforementioned characterization techniques, revealing that their sizes fell within the nanoscale range, not exceeding 70 nanometers. The results indicated a core-shell configuration for the nanomaterials, with the shell comprising the bioceramic component of bioceramic-SiO2-MPS-fruit extract and bioceramic-SiO2-MPS-stem extract.

Effects of berberine and barberry on selected inflammatory biomarkers in adults: A systematic review and dose-response meta-analysis of randomized clinical trials.

The previous meta-analysis showed an advantageous effect of berberine supplementation on interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and serum C-reactive protein (CRP) concentrations; however, it is unknown the dosage that this component influences inflammatory biomarkers. A comprehensive search was done in Scopus, PubMed, and Web of Science until September 2022 to find randomized controlled trials (RCT) that assessed the effects of berberine/barberry on IL-6, TNF-α, and CRP in adults but not trials without a control group. Studies bias was assessed using RoB 2. A random-effects model was performed to calculate the weighted mean difference (WMD). A dose-dependent effect was calculated. Eighteen clinical trials with 1600 participants were included in the current meta-analysis. These interventions significantly mitigate IL-6 levels (-1.18 pg/mL), TNF-α levels (-3.72 pg/mL), and CRP levels (-1.33 mg/L). In addition, the non-linear analysis showed a significant lowering effect of berberine/barberry on IL-6 and TNF-α levels in doses <1000 mg/day and less than 5 weeks of intervention. There are limitations to our findings, including low-quality studies and significant heterogeneity. These interventions might be considered adjunct therapy to managing inflammation status. However, more investigation and high-quality evidence must be conducted to obtain more comprehensive and generalizable results.

Direct Evidence Demonstrates that Puccinia striiformis f. sp. tritici Infects Susceptible Barberry to Complete Sexual Cycle in Autumn.

Wheat stripe rust is an airborne and destructive disease caused by a heteroecious rust fungus Puccinia striiformis f. sp. tritici (Pst). Studies have demonstrated that the rust pathogen accomplishes sexual reproduction on susceptible barberry under natural conditions in spring, whereas Pst infection on barberry is still in blank in other seasons. In late October 2016, aecial production on barberry shrubs were observed in Linzhi, Tibet, China. Therefore, experimental tests were conducted to verify the existence of sexual cycles of Pst in this season. By inoculating 52 aecial clusters from 30 rusted barberry leaves, four Pst samples, T1 to T4, were successfully recovered from the rusted barberry shrubs. Sixty-five single uredinium (SU) isolates were derived from the four Pst samples. Based on virulence tests on the Chinese differential hosts, T1 to T4 samples were unknown races and showed mixed reactions on some differentials. Twenty-one known races and 44 unknown races belonging to five race groups were identified among the 65 SU isolates. Meanwhile, the 65 SU isolates produced 26 various virulence patterns (VPs; called VP1-VP26) on 25 single Yr gene lines and 15 multilocus genotypes (MLGs) at nine simple sequence repeat marker loci. Clustering analysis showed similar lineage among subpopulations and different lineage between subpopulations. Linkage disequilibrium analysis indicated that the SU population was produced sexually. This study first reported that Pst infects susceptible barberry to complete sexual reproduction in autumn. The results update the knowledge of disease cycle and management of wheat stripe rust and contribute to the understanding of rust genetic diversity in Tibet.

Virulence Phenotyping and Molecular Genotyping Reveal High Diversity Within and Strong Gene Flow Between the Puccinia striiformis f. sp. tritici Populations Collected from Barberry and Wheat in Shaanxi Province of China.

Emergence of new Puccinia striiformis f. sp. tritici races that overcome resistance of wheat cultivars is a challenging issue for wheat production. Although sexual reproduction of the fungus on barberry plants under field conditions in the spring in China has been reported, the diversity of the pathogen on barberry plants and the relationship to the population in wheat fields have not been determined. In the present study, two P. striiformis f. sp. tritici populations collected in western Shaanxi Province in May 2016, one from barberry plants (103 isolates) and the other from nearby wheat crops (107 isolates), were phenotyped for virulence and genotyped with simple sequence repeat (SSR) markers. The phenotypic and genotypic data of the two populations were compared to determine their relationships. A total of 120 races, including 29 previously known races (seven were shared by the two populations) and 91 new races (35 from barberry and 56 from wheat), were identified. Similarly, a total of 132 multilocus genotypes, including 51 only from barberry, 77 only from wheat, and four from both, were detected using the SSR markers. Analyses of molecular variance identified high (93%) genetic variance within populations and low but still significant variance (7%) between the populations. Nonparametric multivariate discriminant analysis of principal components and STRUCTURE analysis showed that the two populations had a close relationship with little genetic differentiation (FST = 0.038) and strong gene flow (Nm = 6.34, P = 0.001) between them. Although the analysis of linkage disequilibrium indicated clonal populations, the isolation of P. striiformis f. sp. tritici from barberry plants and the high genetic diversities in the barberry and wheat populations suggest that barberry plants provide aeciospores to infect wheat crops in the area. The information is useful for understanding stripe rust epidemiology and management of the disease.

Magnoflorine from Berberis vulgaris Roots-Impact on Hippocampal Neurons in Mice after Short-Term Exposure.

In search of novel potential drug candidates that could be used as treatments or prophylactics for memory impairment, an aporphine alkaloid magnoflorine (MAG) isolated from the root of Berberis vulgaris was proven to exhibit beneficial anti-amnestic properties. Its effects on immunoreactivity to parvalbumin in the mouse hippocampus were assessed together with a study on its safety and concentration in the brain and plasma. For this purpose, four experimental groups were created: the MAG10 group-treated with 10 mg MAG/kg b.w. i.p., the MAG20 group-treated with 20 mg MAG/kg b.w. i.p., the MAG50 group-treated with 50 mg MAG/kg b.w. i.p., and a control group-injected with saline i.p. at a volume corresponding to their weight. Our results indicated that the hippocampal fields CA1-CA3 were characterized by an elevated number of parvalbumin-immunoreactive neurons (PV-IR) and nerve fibers in mice at the doses of 10 and 20 mg/kg b.w. (i.p.). No significant changes to the levels of IL-1ß, IL-6 or TNF-α were observed for the above two doses; however, the administration of 50 mg/kg b.w. i.p. caused a statistically significant elevation of IL-6, IL-1beta plasma levels and an insignificant raise in the TNF-alpha value. The HPLC-MS analysis showed that the alkaloid's content in the brain structures in the group treated with 50 mg/kg b.w. did not increase proportionally with the administered dose. The obtained results show that MAG is able to influence the immunoreactivity to PV-IR in hippocampal neurons and might act as a neuroprotective compound.

Determination of Hypoglycemic, Hypolipidemic and Nephroprotective Effects of Berberis Calliobotrys in Alloxan-Induced Diabetic Rats.

Many plants of the Berberis genus have been reported pharmacologically to possess anti-diabetic potential, and Berberis calliobotrys has been found to be an inhibitor of α-glucosidase, α-amylase and tyrosinase. Thus, this study investigated the hypoglycemic effects of Berberis calliobotrys methanol extract/fractions using in vitro and In vivo methods. Bovine serum albumin (BSA), BSA-methylglyoxal and BSA-glucose methods were used to assess anti-glycation activity in vitro, while in vivo hypoglycemic effects were determined by oral glucose tolerance test (OGTT). Moreover, the hypolipidemic and nephroprotective effects were studied and phenolics were detected using high performance liquid chromatography (HPLC). In vitro anti-glycation showed a significant reduction in glycated end-products formation at 1, 0.25 and 0.5 mg/mL. In vivo hypoglycemic effects were tested at 200, 400 and 600 mg/kg by measuring blood glucose, insulin, hemoglobin (Hb) and HbA1c. The synergistic effect of extract/fractions (600 mg/kg) with insulin exhibited a pronounced glucose reduction in alloxan diabetic rats. The oral glucose tolerance test (OGTT) demonstrated a decline in glucose concentration. Moreover, extract/fractions (600 mg/kg) exhibited an improved lipid profile, increased Hb, HbA1c levels and body weight for 30 days. Furthermore, diabetic animals significantly exhibited an upsurge in total protein, albumin and globulin levels, along with a significant improvement in urea and creatinine after extract/fractions administration for 42 days. Phytochemistry revealed alkaloids, tannins, glycosides, flavonoids, phenols, terpenoids and saponins. HPLC showed the presence of phenolics in ethyl acetate fraction that could be accountable for pharmacological actions. Therefore, it can be concluded that Berberis calliobotrys possesses strong hypoglycemic, hypolipidemic and nephroprotective effects, and could be a potential therapeutic agent for diabetes treatment.

Acetone extracts of Berberis vulgaris and Cornus mas L. induce apoptosis in MCF-7 breast cancer cells.

Background/aim: This study aimed to determine the proliferation and apoptotic effects of extracts from Cornus mas L. and Berberis vulgaris fruits on human breast cancer cells (MCF-7). Materials and methods: The Cornus mas L. and Berberis vulgaris fruits, which constitute the herbal material of the study, were turned into 80% acetone extract after washing. The total phenolic content in Berberis vulgaris fruit extracts was determined calorimetrically using Folin-Ciocalteu reagent. The spectrophotometric method was used to determine the total flavonoid amount of the extracts. In order to measure the antioxidant capacity of Cornus mas L. and Berberis vulgaris fruits and extracts, DPPH Radical Scavenging Power test and Cu (II) ion reducing antioxidant capacity method were applied. Cell viability rates were determined by the XTT method. Flow cytometric measurement was performed to examine the apoptotic role of the extracts in the cell by using the Annexin-V/7-AAD commercial kit. Results: According to the data, Berberis vulgaris fruit extract appeared more effective on MCF-7 breast cancer cells in both 24 and 48 hours of exposure. Analyses made to examine the phenolic component and antioxidant capacity properties of the fruits used in the study and the results we encountered when we exposed the cell were found to be compatible with each other. Annexin-V/7-AAD method showed that the apoptotic effects of the extracts in 48 hour exposures were more effective. Conclusion: It has been determined that Cornus mas L. and Berberis vulgaris fruits, which are rich in phenolic components with high flavonoid content and high antioxidant capacities, support the apoptosis of cancer cells.

[Mechanism of Berberis atrocarpa anthocyanin against Alzheimer's disease based on network pharmacology and experimental verification].

This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.

Isolation, derivatization, in-vitro, and in-silico studies of potent butyrylcholinesterase inhibitors from Berberis parkeriana Schneid.

Seven known isoquinoline alkaloids 1-7 were isolated from the root extracts of Berberis parkeriana Schneid. Nine new derivatives 8-16 of one of the isolated compounds, jatrorrhizine (7), were synthesized. All the isolated as well as derivatized compounds were evaluated for their in-vitro acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activity. Functionalized compounds selectively exhibited a potent-to-moderate activity with IC50 = 5.5 ± 0.3-124.5 ± 0.4 µM against butyrylcholinesterase enzyme. Among them, compound 15 was a potent BChE inhibitor (IC50 = 5.5 ± 0.3 µM), as compared to the standard drug galantamine hydrobromide (IC50 = 40.83 ± 0.37 µM). Active compounds were further subjected to kinetic, and molecular docking studies to predict their modes of inhibition, and interactions with the receptor (BChE), respectively. Enzyme kinetics studies showed that compounds 9 (IC50 = 25.3 ± 0.5 µM), and 14 (IC50 = 23.9 ± 0.5 µM) were non-competitive inhibitors, while compound 15 exhibited a competitive inhibition. In addition, these compounds were found to be non-cytotoxic against human fibroblast (BJ) cell line, except 9 (IC50 = 17.1 ± 1.0 µM), and 10 (IC50 = 18.4 ± 0.3 µM). Inhibition of cholinesterases is an important approach for development of drugs against Alzheimer's disease, and thus discoveries presented here deserve further investigation.

Novel green synthesis and characterization of a chemotherapeutic supplement by silver nanoparticles containing Berberis thunbergii leaf for the treatment of human pancreatic cancer.

In recent years, silver nanoparticles have been used as modern chemotherapeutic drugs to treat several cancers such as pancreatic, breast, prostate, and blood cancers. No previous reports demonstrated the in vitro anti-human pancreatic cancer effects of the novel chemotherapeutic drug formulated by silver nanoparticles containing Berberis thunbergii leaf (AgNPs). The synthesized AgNPs were characterized using different techniques including UV-vis. and FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy (SEM), and TEM. All techniques approved the synthesized silver nanoparticles. The SEM and TEM exhibited a uniform spherical morphology and an average size of about 15 nm for the biosynthesized nanoparticles, respectively. The 4-(dimethylamino)benzaldehyde,2,2-diphenyl-1- pikrilhydrazil (DPPH) test revealed similar antioxidant potentials for B. thunbergii leaf aqueous extract, AgNPs, and butylated hydroxytoluene. AgNPs inhibited half of the DPPH molecules in the concentration of 108 µg/mL. To survey the anti-human pancreatic cancer activities of AgNO3 , B. thunbergii leaf aqueous extract, and AgNPs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used on common human pancreatic cancer cell lines. AgNPs had very low cell viability and anti-human pancreatic cancer effects dose-dependently against PANC-1, AsPC-1, and MIA PaCa-2. The IC50 values of the AgNPs were 259, 268, and 141 µg/mL against PANC-1, AsPC-1, and MIA PaCa-2 cell lines, respectively. It is thought that the AgNPs obtained can be used as an anticancer drug for the diagnosis of pancreatic cancer in humans after acceptance of the above findings in clinical study trials.

Identification of Mahonia Species as Alternate Hosts for Puccinia striiformis f. sp. tritici and Determination of Existence of Sexual Propagation of the Rust Pathogen on Mahonia Under Natural Conditions in China.

Many Berberis species have been identified as alternate hosts for Puccinia striiformis f. sp. tritici. Importantly, susceptible Berberis species are determined to play an important role in the occurrence of sexual reproduction, generation of new races of the rust pathogen. However, little is known about Mahonia serving as alternate hosts for P. striiformis f. sp. tritici and their role to commence sexual reproduction of the rust fungus under natural conditions. Herein, three Mahonia species or subspecies, Mahonia fortunei, M. eurybracteata subsp. ganpinensis, and M. sheridaniana, were identified as alternate hosts for P. striiformis f. sp. tritici, and seven Mahonia species were highly resistant to the rust pathogen. We recovered seven samples of P. striiformis f. sp. tritici from naturally rusted Mahonia cardiophylla plants. Totally, 54 single uredinium (SU) isolates, derived from the seven samples, generated 20 different race types, including one known race type, and 19 new race types. SNP markers analysis showed that all SU isolates displayed high phenotype diversity (H = 0.32) with a high Shannon's information index (I = 0.49). Analysis of linkage disequilibrium indicated an insignificant rbarD value (rbarD = 0.003, P < 0.1). As a result, all SU isolates are sexually produced, suggesting that P. striiformis f. sp. tritici parasitizes susceptible Mahonia to complete sexual reproduction under natural conditions. The role of Mahonia in occurrence of wheat stripe rust are needed to study for management of the disease.

Effect of Gut Microbiota on the Metabolism of Chemical Constituents of Berberis kansuensis Extract Based on UHPLC-Orbitrap-MS Technique.

The dried stem bark of Berberis kansuensis is a commonly used Tibetan herbal medicine for the treatment of diabetes. Its main chemical components are alkaloids, such as berberine, magnoflorine and jatrorrhizine. However, the role of gut microbiota in the in vivo metabolism of these chemical components has not been fully elucidated. In this study, an ultra-high performance liquid chromatography method coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap-MS) technology was applied to detect and identify prototype components and metabolites in rat intestinal contents and serum samples after oral administration of a B. kansuensis extract. A total of 16 prototype components and 40 metabolites were identified. The primary metabolic pathways of the chemical components from B. kansuensis extract were demethylation, desaturation, deglycosylation, reduction, hydroxylation, and other conjugation reactions including sulfation, glucuronidation, glycosidation, and methylation. By comparing the differences of metabolites between diabetic and pseudo-germ-free diabetic rats, we found that the metabolic transformation of some chemical components in B. kansuensis extract such as bufotenin, ferulic acid 4-O-ß-D-glucopyranoside, magnoflorine, and 8-oxyberberine, was affected by the gut microbiota. The results revealed that the gut microbiota can affect the metabolic transformation of chemical constituents in B. kansuensis extract. These findings can enhance our understanding of the active ingredients of B. kansuensis extract and the key role of the gut microbiota on them.

Development of Synergy-Based Combination of Methanolic Extract of Andrographis paniculata and Berberis aristata Against E. coli and S. aureus.

This study evaluates the antibacterial activity and phytochemical characterizations of Andrographis paniculata extract (APE) and Berberis aristata extract (BAE). The stem of Andrographis paniculata (AP) and root of Berberis aristata (BA) were extracted with methanol. The results confirmed that APE and BAE possess high phenolic and flavonoid content. The antioxidant activity of the APE and BAE showed an elevated potential to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals with IC50 of 95.03 µg/mL and 256.26 µg/mL, respectively. A total of 35 and 32 metabolites in APE and BAE, respectively, were identified through mass spectrometry analysis, whereas 17 and 12 metabolites in APE and BAE, respectively, were detected through high-performance thin-layer chromatography (HPTLC) fingerprinting profiling. Antibacterial activity of the extracts was performed by the well diffusion and microdilution method, and the findings showed that APE and BAE had antibacterial activities against E. coli and S. aureus. The growth curve and time-kill study showed that the extracts had a bacteriostatic effect. A combination study with the standard drug was carried out using the microdilution checkerboard method in which most of the combinations showed synergistic interactions. The findings of this study have shown that APE and BAE are good sources of antibacterial compounds and can be used for treating infectious diseases caused by E. coli and S. aureus.

Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review.

Barberry (Berberis vulgaris L.) is a medicinal plant and its main constituent is an isoquinoline alkaloid named berberine that has multiple pharmacological effects such as antioxidant, anti-microbial, antiinflammatory, anticancer, anti-diabetes, anti-dyslipidemia, and anti-obesity. However, it has restricted clinical uses due to its very poor solubility and bioavailability (less than 1%). It undergoes demethylenation, reduction, and cleavage of the dioxymethylene group in the first phase of metabolism. Its phase two reactions include glucuronidation, sulfation, and methylation. The liver is the main site for berberine distribution. Berberine could excrete in feces, urine, and bile. Fecal excretion of berberine (11-23%) is higher than urinary and biliary excretion routes. However, a major berberine metabolite is excreted in urine greater than in feces. Concomitant administration of berberine with other drugs such as metformin, cyclosporine A, digoxin, etc. may result in important interactions. Thus, in this review, we gathered and dissected any related animal and human research articles regarding the pharmacokinetic parameters of berberine including bioavailability, metabolism, distribution, excretion, and drug-drug interactions. Also, we discussed and gathered various animal and human studies regarding the developed products of berberine with better bioavailability and consequently, better therapeutic effects.