Comprehensive Analysis of Berberis aristata DC. Bark Extracts: In Vitro and In Silico Evaluation of Bioaccessibility and Safety.

Berberine (BER) is an alkaloid found, together with other protoberberinoids (PROTBERs), in several species used in medicines and food supplements. While some herbal preparations containing BER and PROTBERs, such as Berberis aristata DC. bark extracts, have shown promising potential for human health, their safety has not been fully assessed. Recently, the EFSA issued a call for data to deepen the pharmacokinetic and pharmacodynamic understanding of products containing BER and PROTBERs and to comprehensively assess their safety, especially when used in food supplements. In this context, new data were collected in this work by assessing: (i) the phytochemical profile of 16 different commercial B. aristata dry extracts, which are among the most widely used preparations containing BER and PROTBERs in Europe; (ii) the In Vitro and In Silico investigation of the pharmacokinetic properties of BER and PROTBERs; (iii) the In Vitro cytotoxicity of selected extracts in different human cell lines, including tests on hepatic cells in the presence of CYP450 substrates; (iv) the effects of the extracts on cancer cell migration; and (v) the In Vitro molecular effects of extracts in non-cancer human cells. Results showed that commercial B. aristata extracts contain BER as the main constituent, with jatrorrhizine as main secondary PROTBER. BER and jatrorrhizine were found to have a good bioaccessibility rate, but they interact with P-gp. B. aristata extracts showed limited cytotoxicity and minimal interaction with CYP450 substrates. Furthermore, tested extracts demonstrated inhibition of cancer cell migration and were devoid of any pro-tumoral effects in normal cells. Overall, our work provides a valuable overview to better elucidate important concerns regarding botanicals containing BER and PROTBERs.

Berberis integerrima bioactive molecules loaded in chitosan-based electrospun nanofibers for soybean oil oxidative protection.

Natural bioactive molecules such as phenolic acids and alkaloids play a crucial role in preserving the quality and safety of food products, particularly oils, by preventing oxidation. Berberis integerrima, a rich source of such antioxidants, has been explored in this study for its potential application in soybean oil preservation. Electrospun nanofibers, composed of polyvinyl alcohol and chitosan, were fabricated and loaded with an alcoholic extract of Berberis integerrima. The antioxidant activity of Berberis integerrima was evaluated, and the phenolic compounds contributing to its efficacy were identified and quantified. The physicochemical properties of the polyvinyl alcohol /chitosan/Berberis integerrima nanofibers, including morphology, crystallinity, functional groups, and thermal stability, were characterized. The results revealed that the polyvinyl alcohol/chitosan/Berberis integerrima nanofibers exhibited high antioxidant capacity and improved the stability of Berberis integerrima, indicating their potential as effective and biodegradable materials for food preservation. This study underscores the potential of harnessing natural antioxidants from Berberis integerrima in nanofibers to enhance the quality and safety of soybean oil.

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.

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.

Evaluation of the effectiveness of Berberis integerrima Bunge root extract combined with spearmint essential oil in the treatment of acne vulgaris: A randomized controlled clinical trial.

BACKGROUND: Acne vulgaris is one of the most common dermatological disorders. Berberis integerrima Bunge belongs to the Berberidaceae family. Several studies on different Berberis species in addition to B. integerrima have shown antimicrobial, antioxidant, and anti-inflammatory effects. Spearmint essential oil also has antioxidant, antibacterial, and anti-inflammatory activities. This study aimed to evaluate the clinical effectiveness of the topical combination of B. integerrima root extract and spearmint essential oil in the treatment of acne vulgaris. METHODS: Patients with mild to moderate facial acne who met the inclusion criteria were randomly assigned to either drug (B. integerrima extract/spearmint essential oil topical solution) or control (clindamycin 1% topical solution) groups. Each group applied the solution twice a day for 4 weeks. Before and at the end of the intervention, the number of lesions and mGAGS (Modified Global Acne Grading Scale) score were recorded. RESULTS: Thirty patients in each group of drug and control completed the study. Topical B.integerrima root extract/spearmint essential oil significantly reduced the number of lesions (27.33 ± 26.17 vs. 21.58 ± 21.10; p < 0.001) and mGAGS (18.76 ± 8.61 vs. 13.87 ± 8.14; p < 0.001) at the end of the intervention. However, there was no significant difference between the two groups regarding the number of lesions (p = 0.906) and mGAGS (p = 0.882). CONCLUSIONS: B. integerrima root extract combined with spearmint essential oil has significant anti-acne effects, comparable to topical antibiotic clindamycin. It could be considered as a potential treatment for acne vulgaris. However, more studies with larger sample sizes and longer durations are required to confirm this effect.

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.

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.

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.

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.

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.

Buccal spray of standardized Berberis aristata extract causes tumour regression, chemoprotection and downregulation of inflammatory mediators in oral cancer hamster model.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberis aristata (BA) has been described in Ayurveda in formulations for treating conditions related to the buccal cavity, including tumours and inflammation. Oral cancer (OC) is a major global health problem with high rates of recurrence and metastasis. Natural product based therapies are being explored as safer therapeutic strategies for OC. AIM OF THE STUDY: Evaluating the potential of standardized BA extract loaded buccal spray formulation in OC. MATERIAL AND METHODS: BA stem bark extract was prepared using sonication and standardized with respect to Berberine. The standardized extract was characterized and formulated as a buccal spray (SBAE-BS) using hydroxyl propyl methyl cellulose K15M, polyethylglycol 400, Miglyol®812N and ethanol. The SBAE-BS was characterized and evaluated in vitro in KB cell line and in vivo in OC hamster model. RESULTS: The SBAE-BS had pH, viscosity, mucoadhesive strength and BBR content corresponding to 6.8, 25.9 cP, 345 dyne/cm2 and 0.6 mg/mL respectively. In vitro cytotoxicity of SBAE-BS was comparable to 5 fluorouracil (5FU). In hamsters, SBAE-BS treatment lead to tumour regression (p = 0.0345), improved body weights (p < 0.0001), no organ toxicity, downregulation of inflammatory mediators and improved survival outcomes as compared to standard systemic 5FU. CONCLUSION: Thus, SBAE-BS showed cytotoxic and chemo-protective effects in the OC hamster model, evidencing its ethnopharmacological use and demonstrating translational potential to be developed as therapy for OC.

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.

Total phenolic, monomeric anthocyanin content and antioxidant activity of Berberis commutata Eichler fruits / Contenido fenólico total, antocianinas monoméricas y actividad antioxidante de los frutos de Berberis commutata Eichler

Background: Berberis commutata Eichler is a berry that grows in the Peruvian Andes and has been consumed in the Andes of South America since ancient times. The edible fruits have an intense purple color and are rich in anthocyanins and phenolic compounds that are available from February until May each year. The color of the fruits is a soft purple dye for natural fibers, and many birds use them as food. Objective: This study quantified the total phenolic, monomeric anthocyanin content and antioxidant activity of Berberis commutata Eichler berries. Methods: The total phenolic content was determined by the Folin-Ciocalteu colorimetric assay. Monomeric anthocyanin content was determined by the method is pH differential, and the antioxidant activity was measured using the Brand-Williams method. Results: The total phenolic content was 7,490 ± 0.85 mg GAE/100g, and the monomeric anthocyanin content was 70 ± 0.03 mg/100g. The antioxidant activity of the berries showed a tendency to increase with B. commutata extract concentration; an EC50 of 0.91 mg/mL was calculated, indicating a high antioxidant power. Conclusion: Our results showed that B. commutata E. has both high total phenolic content and monomeric anthocyanins comparable to other superfruits and high antioxidant activity, which means that it is possible to use this berberis species as a functional food.

Introducción: Berberis commutata Eichleres una baya que crece en los Andes peruanos. Los frutos comestibles tienen un intenso color púrpura rico en antocianinas y componentes fenólicos que están disponibles desde febrero hasta mayo de cada año. El color de sus frutos se utiliza como un suave colorante púrpura para las fibras naturales y muchas aves los utilizan como alimento. Sin embargo, desde la antigüedad los frutos de esta especie han sido consumidas en los Andes de Sudamérica. Objetivo: Este estudio cuantificó el contenido fenólico total, antocianinas monoméricas y la actividad antioxidante usando el método del radical DPPH de las bayas de Berberis commutata Eichler. Método: El contenido fenólico total se midió a través del ensayo colorimétrico de Folin-Ciocalteu, el contenido de antocianinas monoméricas se determinó mediante el método del pH diferencial y la actividad antioxidante se midió con el método de Brand-Williams. Resultados: El contenido fenólico total fue de 7,490 ± 0.85 mg GAE/100g y el contenido de antocianinas monoméricas fue de 70 ± 0.03 mg/100g. La actividad antioxidante de las bayas mostró una tendencia a aumentar con la concentración del extracto de B. commutata, se calculó un EC50 de 0.91 mg/mL que indica un alto poder antioxidante. Conclusión: Nuestros resultados mostraron que B. commutata E. tiene tanto un alto contenido fenólico total, así como antocianinas monoméricas comparables con otras superfrutas y una elevada actividad antioxidante, lo que significa que es posible utilizar esta especie de berberis como alimento funcional.

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.

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.

Antioxidant, Antibacterial, and Antifungal Activities of the Ethanolic Extract Obtained from Berberis vulgaris Roots and Leaves.

This work assessed the phenolic and flavonoid components and their antioxidant, antifungal, and antibacterial effects in the ethanolic extract of barberry leaf and roots. The antibactericidal activity of root and leaf extracts against pathogenic bacteria was tested using agar diffusion and microdilution broth production for the lowest inhibitory concentration (MIC). Berberis vulgaris root and leaf extracts inhibited Staphylococcus aureus ATCC9973, Escherichia coli HB101, Staphylococcus enteritis, and Escherichia coli Cip812. The disc assay technique was used to assess the bactericidal activity of the extracts versus both pathogenic Gram-positive and Gram-negative strains. Hydro alcoholic extract was more effective against bacterial than fungal strains. The results showed that Berberis vulgaris leaf and roots extract had similar antifungal activities. Berberis vulgaris root extract inhibited the mycelial growth of Penicillium verrucosum, Fusarium proliferatum, Aspergillus ochraceous, Aspergillus niger, and Aspergillus flavus. Berberis vulgaris root extract has excellent antioxidant, antibacterial, and antifungal effects. Berberis vulgaris exhibited antimicrobial activity in vitro, and MIC showed that Berberis vulgaris parts efficiently affected pathogens in vitro. In conclusion, both Berberis vulgaris roots and leaves have considerable antibacterial activity and can be used as a source of antibacterial, antioxidant, and bioactive compounds to benefit human health.

Metabolic profile and antioxidant capacity of five Berberis leaves species: A comprehensive study to determine their potential as natural food or ingredient.

A comprehensive study of bioactive compounds was carried out in the leaves of the main Berberis species growing in Chile (Berberis microphylla, Berberis darwinii, Berberis empetrifolia, Berberis trigona, and the introduced Berberis vulgaris). We identified 117 compounds, by a detailed analysis of each molecule, including phenolic acids, alkaloids, flavonols, and other compounds, using high-performance liquid chromatography and high-resolution mass spectrometry. Quantitative analysis of main compound was also included for all species. Hydroxycinnamic acid derivatives were the main compounds in all the studied leaves, with the highest concentration in Berberis microphylla. Quercetin derivatives were the most relevant flavonols in all species, except in Berberis vulgaris, in which isorhamnetin-3-rutinoside was the most concentrated. The fatty acid profile, determined by gas chromatography mass spectrometry revealed the presence of linoleic and linolenic acids in all species studied. Berberis vulgaris showed higher levels of these fatty acids. The antioxidant capacity, explored by three in vitro methods, showed high values for all studied Berberis species. The obtained levels are higher than those of other prominent foods. The findings will inform novel approaches for the valorization of these leaves as natural food or ingredient.

Comparative studies of anticancer, antimicrobial, antidiabetic, antioxidant activities of Daphne oleoides and Berberis baluchistanica extracts native to Pakistan.

To investigate in vitro anticancer, antimicrobial, antioxidant and in vivo hypoglycaemic effects of crude methanolic extracts (CMEs) of Berberis baluchistanica and Daphne oleoides. MTT assay for cytotoxicity on HeLa and NIH cells, disc diffusion protocols for antimicrobial and DPPH assay for antioxidant potential were applied. In vivo hypoglycaemic effect was investigated on Alloxan-induced diabetic rabbits. D. oleoides CME exhibited moderate cytotoxic behaviour against HeLa cells (IC50 77.87µg/mL) whereas B. baluchistanica CME was found deficient (IC50 170.02µg/mL). P. aeruginosa was susceptible to both CMEs. M. luteus and B. subtilis was prone to the bactericidal effects of D. oleoides and B. baluchistanica CMEs respectively. D. oleoides CME inhibited more than 80% S. cerevisiae and 60% C. glabrata colonies. B. baluchistanica CME showed significant antioxidant activity (IC50 52.86µg/ml) than D. oleoides CME (IC50 87.30µg/ml) and standard resveratrol (IC50 109.46µg/ml). B. baluchistanica CME showed superior antidiabetic effect (135.75 mg/dl ±0.53) as compared to D. oleoides CME (191.50 mg/dl ± 0.48) but less antidiabetic effect than metformin hydrochloride (standard). All the above potentials exhibited by D. oleoides and B. baluchistanica CMEs propose further investigations to isolate and purify responsible biologically active lead molecule(s) with diverse capabilities.

Berberis dictyophylla F. inhibits angiogenesis and apoptosis of diabetic retinopathy via suppressing HIF-1α/VEGF/DLL-4/Notch-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao Bopi (XBP, སྐྱེར་བའི་བར་ཤུན།), as a classical Tibetan medicinal plant in China, which derived from the stem bark of Berberis dictyophylla F., has the function of "clearing heat and decreasing mKhris-pa". And it traditionally is utilized to treat the diabetes mellitus and its complications, such as diabetic retinopathy (DR). However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The purpose of this study aimed to explore the microvascular protection of water extract of XBP against the spontaneous retinal damage of db/db mice. Meanwhile, the underlying mechanisms of XBP on angiogenesis and apoptosis were further interpreted. MATERIALS AND METHODS: We firstly used high-performance liquid chromatography to detected the representative chemical ingredients in the water extract of XBP. The DR model of db/db mice was then randomly divided into five groups: model group, calcium dobesilate (0.23 g/kg) group, and the water extract of XBP (0.375, 0.75 and 1.5 g/kg, respectively) groups. After 8 weeks of continuous administration, the parameters including body weight, fasting blood glucose, oral glucose tolerance test and insulin tolerance test were measured. The pathological changes and abnormal angiogenesis of the retina were detected by optical coherence tomography, HE, periodic acid-Schiff staining and transmission electron microscopy. Simultaneously, molecular docking was used to predict the potential connections between representative ingredients in XBP and angiogenesis/apoptosis-related proteins. The level of angiogenesis-related proteins and gene hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth (VEGF), delta-like ligand 4 (DLL-4) and Notch-1 were estimated by immunofluorescence analyses and real time-PCR. Further, TUNEL staining and immunofluorescence analyses were performed to investigate the apoptotic phenomenon and the expression of Bax, Bcl-2, Apaf-1, Cyto-c and cleaved caspase-3 and cleaved caspase-9 in the retina. RESULTS: Phytochemical analysis revealed that magnoflorine, jatrorrhizine, palmatine and berberine were principally representative ingredients in XBP. The results demonstrated that XBP effectively increased glucose tolerance and insulin sensitivity, whereas no effect on body weight of DR mice. Moreover, retinal thickening, pathological and retinal ultrastructure changes in DR mice were evidently ameliorated by XBP. The molecular docking results demonstrated that the main components of XBP and the protein of angiogenesis and apoptosis had a potential bind. XBP restrained the gene and protein levels of HIF-1α, VEGF, DLL-4 and Notch-1 in retina. Additionally, the TUNEL-positive cell rate and the down-regulated proteins of Bax, Apaf-1, Cyto-c, cleaved Caspase-3 and cleaved Caspase 9 and increased Bcl-2 level were revised by XBP. CONCLUSIONS: To sum up, the results suggested that XBP against DR could attribute to alleviating angiogenesis and apoptosis by suppressing the HIF-1α/VEGF/DLL-4/Notch-1 pathway. This evidence sheds a new light on the potential mechanisms of XBP in the treatment of DR.

Determination of antioxidant and bimolecular protective effect of Berberis calliobotrys Aitch. ex Koehne extracts and essential oil against H2O2 induced oxidative damage to pBR 322 DNA and RBCs.

We investigated the protective effect of fractions and essential oil from Berberis calliobotrys on H2O2 induced oxidative damage on pBR322 DNA. The crude plant material was extracted using 90% methanolic and liquid-liquid fractionation was accomplished. The essential oil analysis was performed using GC/MS. The FRAP and DPPH assays were performed to determine antioxidant activity. The DNA protection assay was performed using plasmid pBR 322 DNA. The essential oil analysis indicated presence of germacrene D (9.26%), stearic acid (7.50%), methyl tetradecanoate (6.36%) α-thujene (5.71%) and α-muurolol (5.30%) methyl eugenol (5.17%). In vitro analysis showed significant antioxidant activity of all tested extracts and essential oil. The extract showed significant effects at (1000 µg/mL) on pBR322 DNA. Finally it was concluded that Berberis calliobotrys possesses signifgant protective on effects pBR322 DNA and RBC cellular membrane.