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Genus Berberis is an excellent choice for research due to its history in traditional medicine, diverse pharmacological properties, and it has potential for drug discovery. This review presents information on the ethnobotany, pharmacological activities, and many phytochemicals identified from Berberis species. It examines the existing literature on the genus Berberis, drawn from online databases, including PubMed, Web of Science, Science Direct, Elsevier, and Google Scholar, etc encompassing the data from 1960 to 2023. This review focuses on the structural details of reported phytochemicals of Berberis species and pharmacological actions. Different extraction techniques were evaluated for extracts preparation. According to literature review, phytochemical analysis exhibited the presence of alkaloids, flavonoids, and phenolic compounds. A major bioactive alkaloid, berberine exhibits its main role in treatment of many gastric, infectious, and chronic disorders. This literature indicates that Berberis genus exhibits a variety of biological activities, i.e anti-inflammatory, cytotoxic, hepatoprotective, antimicrobial, antidiabetic and antioxidant activities and utilization of these effects in the treatment and management of various diseases, like diabetes, microbial infections, inflammation, liver disorders, and cancer. However, conventional medicines, validation of traditional uses, and in-depth phytochemical analysis are areas of research in genus Berberis., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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.

In the present study, magnesium nanoparticles (Mg NPs) were synthesized utilizing an aqueous extract of Berberis aristate rhizome and evaluated for antimicrobial and anti-inflammatory activity. Technofunctional properties of rhizome powder were evaluated and during thermal stability evaluation four stages of decomposition with a maximum delta Y value of 76.04 % was observed. Optimization of Mg NPs was carried out by employing eight different concentrations (C1-C8)   and the C4 showed maximum absorbance at 330 nm confirming the NPs synthesis. The Mg NPs showed the particle size of 62 nm, zeta potential of -24.7 mV and hexagonal mprphology. Potential inhibition against S. aureus and E. coli (76.78 ± 0.05% and 74.62 ± 0.17%)and anti-inflammatory activity ranging from 42.43 ± 0.07-82.92 ± 0.04% was observed for Mg NPs. Therefore, green synthesis of Mg NPs is a promising approach for the development ofbiological active NPs to cure microbial infections.

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., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 EC 50 FRAP = 0.1398 mg/mL, IC 50 ABTS = 0.0442 mg/mL, IC 50 DPPH = 0.2610 mg/mL compared to ascorbic acid (IC 50 = 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 (IC 50 < 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. ( 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 IC 50 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.

Being an important source of berberine, Berberis chitria Buch.-Ham. ex Lindl. (Berberidaceae) has high demand in pharmaceutical industries. Its populations are diminishing due to overexploitation, habitat loss, slow-growing nature, and climate change. It is important to develop propagation protocols to sustain its natural populations and ensure its survival in the future. Fertilizers play an essential role in the yield and productivity of different crops. Among others, urea is the most abundantly used fertilizer in crops. Its effects on the yield and survival of medicinal plants are poorly studied. However, it is known that applying urea for a long time affects the soil negatively. Due to these negative effects, alternative fertilizers such as graphene-based metal composite (GMC) are being tested for their efficiency. In the present study, for the first time, we tested the effects of urea and GMC on the germination and performance of B. chitria. GMC showed maximum germination at 30 ppm (75%) and urea at 15 ppm (79%). Findings reveal non-significant effects of GMC and urea on germination and performance of B. chitria, suggesting the use of GMC as an alternative fertilizer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Berberis lycium is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer's effect of berberine isolated from Berberis lycium., Methods: Root extract of B. lycium was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer's disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and β-secretase., Results: During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis. In vivo EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer's disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p<0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of β-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with β-secretase in docking studies. Binding energies for interaction of β-secretase with berberine and drug Rivastigmine is -7.0 kcal/mol and -5.8 kcal/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer's disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing β-secretase expression in the Alzheimer's disease model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ismail et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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., Competing Interests: Conflict of interest: The authors declare that there are no relevant financial or nonfinancial competing interests to report., (© TÜBİTAK.)

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-1β, 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.

Introduction: The root bark of Berberis aristata has been utilized by indigenous peoples for wound treatment for centuries. The mature root barks are crushed into a paste and applied to the wound's surface., Objective: The focus of this research is to analyse the wound healing activities of an ethanolic extract of Berberis aristata, as well as to use molecular docking to establish the likely mechanism of the potent phytochemical. There is no scientific evidence to support the usage of root bark extract of Berberis aristata., Methods: The Herbal ointment, which comprises (1%, 2%, and 4% w/w) ethanolic extract of root bark, was developed to test the wound healing ability of incision and excision wounds, and the molecular mechanism was established using Auto-Dock software., Results: Epithelization stage, wound index, % wound contraction area, hydroxyproline content, DNA estimate, and histopathological assessments were performed on the incision wound model. Tensile strength was assessed in an excision wound model. TLC was used to identify the samples after successive extractions with different solvents based on polarity., Conclusion: Berberine and tetrahydropalmatine were major active phytoconstituent found in root barks of Berberis aristata as secondary metabolites. Animals treated with 4% w/w formulation demonstrated considerable wound contraction, epithelization time, and wound index in the excision model. In contrast, to control and standardize the concentrations of hydroxyproline, total amino acids, and DNA in recovering tissue were higher. At 4% w/w extract formulation, the parameters studied indicated a substantial result. Berberine and tetrahydropalmatine, active metabolites which are present in the ethanolic extract of Berberis aristata, were found to be responsible for wound healing. Based on ligand interactions, the findings verified Berberis aristata ethnomedicinal claim in a wound healing capacity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Since ancient times the medicinal plants have been under use as food and potential therapeutic agent for the management of overall health and the use of all plant parts including fruits, seeds, is well reported in the literature. One such plant is Berberis aristata which is rich in vitamins, minerals, and various phytochemicals amongst which Berberine is the principal bioactive compound with a range of reported health benefits, and some of the commercial formulations like Rasaut, Darvyadi Leha are being used for the treatments of jaundice, malaria, typhoid fever, inflammation, eye infection, diarrhea, wound healing, etc. The hepatoprotective, antidiabetic, antitumor, anti-cancerous, properties are the recent additions to its functional importance. Berberine has significant bioactivities in the treatments of different diseases. Besides its remarkable applications, the berberine has low efficacy due to its low solubility in water, poor absorption, and low bioavailability. This problem can be solved by using some techniques like Nanotechnology which has been found to increase its solubility in water, bioavailability, and absorption and hence provide a better delivery system of berberine. This review illuminates the therapeutic applications of the plant Berberis aristata , scientific validation to its traditional uses, role of berberine in the treatment of various diseases through its different bioactivities, major flaws in berberine treatment, and the role of nanotechnology in minimizing those flaws and increasing its overall efficacy.Key teaching pointsPlant Berberis aristata has been used since ancient times for the treatment of various ailments like jaundice, hepatitis, fever, bleeding, inflammation, diarrhea, malaria, skin and eye infections, chronic rheumatism, and urinary disorders.Berberine is the major and most significant phytochemical among numerous phytochemicals present in plant Berberis aristata.Berberine has significantly shown many potent effect against emerging diseases like cancer and diabetes. Besides that, it has also shown antioxidant, anti-inflamation, antimicrobial, hepatoprotective, and anti-gastrointestinal disorder properties.Berberine can be very effective in overcoming the demerits of berberine treatment like poor aqueous solubility, low bioavailability, and poor absorption in the human body in the treatment of various diseases.

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 - β -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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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 IC 50 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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Berberis integerrima commonly known as "barberry" belongs to the Berberidaceae family and has been used as a medicinal plant in Iranian traditional medicine., Aim of the Study: Our aim in this study was to investigate the effects of barberry consumption on blood pressure (BP)., Materials and Methods: 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., Results: Seventy-eight participants with an average age of 54.12 ± 10.32 years and BMI of 27.93 ± 2.22 kg/m 2 completed the study. There was no significant difference in body weight, physical activity, and the 24-h urinary sodium and potassium excretion between the two groups before and after the study. After adjusting for baseline values and changes in sodium intake, systolic, and mean arterial BP decreased significantly in the barberry group compared to the placebo group (p = 0.015 and p = 0.008, respectively). Plasma NOx levels and ACE activity were not different between the two groups, but urinary NOx was increased significantly in the barberry group compared to the placebo group (p = 0.008)., Conclusions: In patients treated with antihypertensive drugs, daily consumption of purple-black barberry can be effective in improving systolic BP control., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Antioxidants are materials that scavenge or remove free radicals from living systems. The oxidation process ends in the production of free radicals. These free radicals are the chief birthplace of cancerous cells. Antioxidizing agents remove free radical intermediates by terminating oxidation processes by being oxidized themselves. On the other hand, infectious diseases affect the world on a large scale. To fight these diseases several synthetic compounds have been used. Plant based medications play important role in this regard. So, the current research aimed to investigate the antibacterial and antioxidant effect of Berberis lycium Royle root bark (BLR) extract. Berberis lycium Royle was used for phytochemical analysis and also as antimicrobial and antioxidant agents. The antimicrobial activity was evaluated by the agar well diffusion method. Current study revealed that BLR was rich in phytochemicals and toxic against tested pathogenic bacteria. BLR showed the highest activity against S. pyogenes (13.3±0.8 mm). The lowest antibacterial activity was reported against E. coli (0±0 mm). In case of minimum inhibitory concentration, it was observed that BLR with 10 μg/mL concentration showed the highest activity while 2.5 μg/mL of BLR showed the least inhibitory activity. The highest In vitro antioxidant activity was recorded as 65% at 100 µg/mL. In case of in vivo antioxidant activity level of CAT, GSH and SOD were decreased while that of MDA was enhanced in groups treated with CCl4 as compared to the control group. BLR extract treatment reversed all these changes significantly. Current results indicate that BLR is effective against bacterial pathogens and also has antioxidant potential.

Wild fruits have increasingly been investigated as part of recent searches for food products with a high antioxidant activity. In this study, wild edible berberis Berberis vulgaris collected from three different provinces (Jilin, Heilongjiang, and Liaoning) were investigated for their phenolic contents, organic acid contents, mineral contents, antioxidant activity as well as their antimicrobial potential against a range of common food borne pathogens. In addition, a physiochemical and mineral analysis of the fruits was also performed. The methanol extracts of berberis fruit collected from Jilin province were highly active against all the studied food borne bacterial pathogens, i.e., S. aureus and L. monocytogenes , E. coli , P. fluorescens , V. parahaemolyticus , and A. caviae while the berberis extracts from Heilongjiang and Liaoning showed activity only against Gram-negative bacteria. The phenolic content and antioxidant activity were determined by the HPLC separation method and β-carotene bleaching methods, respectively. Four organic acids such as malic acid, citric acid, tartaric acid, and succinic acid were identified while a variety of phenolic compounds were detected among which catechin, chlorogenic acid, and gallic acid were found to be the predominant phenolic compounds in all three of berberis fruit samples. The berberis fruit from Jilin was found to be superior to the Heilongjiang and Liaoning fruit regarding desired physiochemical analysis; however, there were no significant differences in the mineral contents among the three samples. Overall, the berberis fruit from Jilin was ranked as the best in term of the nutritional, physiochemical, antimicrobial, and antioxidant properties. This study confirms the various useful characteristics and features of berberis at a molecular level that can be used as a sustainable source for their potential nutritional applications for making functional foods in different food industries.

Background: The plant Berberis aristata is traditionally used and scientifically validated for treating obesity and hyperlipidemia. It is also traditionally used to treat gynecological abnormalities. Therefore, the present study was designed to evaluate the therapeutic potential of Berberis aristata for obesity-related reproductive changes and chemically characterize it., Methods: High-fat diet was given to 36 female rats for six weeks to induce obesity and infertility. These obese rats were treated with 10 mg/kg orlistat or the plant extract at 125-500 mg/kg for 45 days., Results: The GC-MS analysis of the plant extract included fructose, thymic acid and other hydrocarbons. The plant extract revealed a remarkable free radical scavenging activity. The treated animals exhibited a decrease in total cholesterol and triglycerides (p<0.001), insulin and leptin levels (p<0.05), visceral fat, and body weight while increasing the estradiol level at 500 mg/kg dose of the plant extract as compared with untreated animals as demonstrated from the histology of the ovary. Oxidative stress biomarkers such as superoxide dismutase, nitric oxide, malondialdehyde and reduced glutathione were significantly (p<0.01-0.001) ameliorated in treated rats., Conclusion: B. aristata exhibited substantial potential against obesity-inducedreproductive damage in female rats by reducing oxidative stress and resistance to leptin and insulin., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Interest in medicinal plants and fruits has increased in recent years due to people beginning to consume natural foods. This study aims to investigate the total phenolic flavonoid content, antioxidant activity, condensed tannin content, oil content, and fatty acid compositions of five local breeds of Berberis spp. from Bayburt, Turkey, and their antioxidant and antimicrobial activities. The fatty acid composition of samples was performed with gas chromatography-mass spectrometry (GC-MS), and the total fatty acid content of samples was between 6.12% and 8.60%. The main fatty acids in Berberis spp. samples were α-linolenic acid (32.85-37.88%) and linoleic acid (30.98-34.28%) followed by oleic acid (12.85-19.56%). Two antioxidant assays produced similar results, demonstrating that extracts of wild B. vulgaris L. had the highest ferric reducing antioxidant power (FRAP) (621.02 μmol FeSO 4 .7H 2 O/g) and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (0.10 SC 50 mg/mL) values. According to principal component analysis (PCA), four components were determined. In addition, two main groups were determined according to hierarchical cluster analysis (HCA), and wild and culture of B. vulgaris L. were in different subgroups. This is the first original report about the fatty acid composition and oil content of Berberis spp. grown in Bayburt, Turkey. The obtained results indicate that B. integerrima Bunge and B. vulgaris , which have especially remarkable fatty acid content, antioxidant, and antimicrobial activity, could be potential sources for these properties in different areas of use.

Palmatine (PLT) is a natural isoquinoline alkaloid that belongs to the class of protoberberines and exhibits a wide spectrum of pharmacological and biological properties, including anti-cancer activity. The aim of our study was to isolate PLT from the roots of Berberis cretica and investigate its cytotoxic and anti-proliferative effects in vitro alone and in combination with doxorubicine (DOX) using human ER + /HER2 - breast cancer cell lines. The alkaloid was purified by column chromatography filled with silica gel NP and Sephadex LH-20 resin developed in the mixture of methanol: water (50:50 v / v ) that provided high-purity alkaloid for bioactivity studies. The purity of the alkaloid was confirmed by high resolution mass measurement and MS/MS fragmentation analysis in the HPLC-ESI-QTOF-MS/MS-based analysis. It was found that PLT treatment inhibited the viability and proliferation of breast cancer cells in a dose-dependent manner as demonstrated by MTT and BrdU assays. PLT showed a quite similar growth inhibition on breast cancer cells with IC 50 values ranging from 5.126 to 5.805 µg/mL. In contrast, growth of normal human breast epithelial cells was not affected by PLT. The growth inhibitory activity of PLT was related to the induction of apoptosis, as determined by Annexin V/PI staining. Moreover, PLT sensitized breast cancer cells to DOX. Isobolographic analysis revealed synergistic and additive interactions between studied agents. Our studies suggest that PLT can be a potential candidate agent for preventing and treating breast cancer.

In this study, zero-valent iron (GnZVI) was synthesized using barberry leaf extract (GnZVI@BLE). The physicochemical properties of the final products were characterized by FT-IR, SEM, TEM, and EDS techniques. The results of TEM analysis showed that the obtained iron zero-valent nanoparticles with a diameter between 20 and 40 nm and shell-core structures were successfully synthesized. The results of FT-IR confirmed the presence of various functional groups. The photocatalytic activity of synthesized nanoparticles was investigated by reduction of hexavalent chromium. Laboratory data showed that the presence of GnZVI@BLE as a nanocatalyst in the photocatalytic process could be reduction the hexavalent chromium (Cr (VI)). Photocatalytic data revealed that, when the dosage of nanoparticles was 0.675 g/L, the reduction efficiency of hexavalent chromium was 100%. The kinetics of the reaction follows a pseudo-second-order equation. The constant of reaction rate was 0.4 at pH 2 and 0.5 g/L concentration of GnZVI@BLE., (Copyright © 2021. Published by Elsevier Inc.)

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in men over the age of 50. Clinical studies have suggested that chronic inflammation is associated with BPH pathoprogression. Berberine (BB) is a natural compound found in Berberis vulgaris , Coptis chinensis and Phellodendron amurense. Although several studies have documented that BB may be effective for inflammation, the effects of the oral administration of BB on BPH are not fully understood. The effects of BB on chronic prostatic inflammation were evaluated in a testosterone-induced BPH animal model. Orally administered BB alleviated the pathological alterations induced by BPH and significantly suppressed the expression of inflammatory markers while enhancing the expression of antioxidant factors. Furthermore, BB regulated the activation of macrophages via NF-κB signaling pathway inhibition in the BPH rat model. The effects and underlying signaling pathway of BB in RWPE-1 cells exposed to macrophage conditioned medium (CM) were also demonstrated in vitro . While CM stimulation induced prostatic cell proliferation and upregulated the expression of inflammatory factors, BB exerted anti-proliferation and anti-inflammatory effects in RWPE-1 cells. These findings propose that BB suppresses androgen-dependent BPH development by targeting NF-κB-mediated pro-inflammatory signaling.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Pyranoanthocyanins are anthocyanin-derived pigments with higher stability to pH and storage. However, their slow formation and scarcity in nature hinder their industrial application. Pyranoanthocyanin formation can be accelerated by selecting anthocyanin substitutions, cofactor concentrations, and temperature. Limited information is available on the impacts of the chemical structure of the cofactor and anthocyanin; therefore, we evaluated their impacts on pyranoanthocyanin formation efficiency under conditions reported as favorable for the reaction. Different cofactors were evaluated including pyruvic acid, acetone, and hydroxycinnamic acids ( p -coumaric, caffeic, ferulic, and sinapic acid) by incubating them with anthocyanins in a molar ratio of 1:30 (anthocyanin:cofactor), pH 3.1, and 45 °C. The impact of the anthocyanin aglycone was evaluated by incubating delphinidin, cyanidin, petunidin, or malvidin derivatives with the most efficient cofactor (caffeic acid) under identical conditions. Pigments were identified using UHPLC-PDA and tandem mass spectrometry, and pyranoanthocyanin formation was monitored for up to 72 h. Pyranoanthocyanin yields were the highest with caffeic acid (~17% at 72 h, p < 0.05). When comparing anthocyanins, malvidin-3- O -glycosides yielded twice as many pyranoanthocyanins after 24 h (~20%, p < 0.01) as cyanidin-3- O -glycosides. Petunidin- and delphinidin-3- O -glycosides yielded <2% pyranoanthocyanins. This study demonstrated the importance of anthocyanin and cofactor selection in pyranoanthocyanin production.

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]&#95;gauvreauii&#95;Group, Escherichia Shigella, Enterococcus, Fusobacterium, Holdemanella, and Prevotella&#95;9 in T2D rats. Additionally, correlation analysis revealed that Akkermansia was positively correlated with ISI, while [Ruminococcus]&#95;gauvreauii&#95;Group, Collinella, Escherichia Shigella, Enterococcus, Fusobacterium, Holdemanella and Prevotella&#95;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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

As isoquinoline alkaloid naturally occurs in Coptis and Berberis species, berberine (BER) has shown anti-oxidant, anti-tumour, anti-bacterial and hepatoprotective activities and beneficial effects against digestive, cardiovascular and neurological conditions. Also, BER antiinflammatory, pain-relieving and anti-cholinesterase activities were widely studied. The present overview discusses the analgesic effects of BER. Based on the literature, BER exerted pain-relieving activity against diabetic and chemotherapy-induced neuropathy, and sciatic nerve injury-induced pain via down-regulation of transient receptor potential vanilloid 1, suppression of NF-κB and modulation of μ and δ opioid receptors. Besides, BER could repress inflammatory markers tumour necrosis factor-α, interleukin-6 and IL-1β, as well as prostaglandin E2, inducible nitric oxide synthase and cyclooxygenase-2. The modulatory effects of BER on dopamine and N-methyl d-aspartate systems were also noted. Moreover, BER could induce Nrf2 expression but inhibits p38-MAPK and STAT3 phosphorylation. Noteworthy, anti-cholinesterase activity, which may potentially contribute to BER analgesic properties, warrants particular attention., (© 2020 John Wiley & Sons, Ltd.)

Neurodegenerative diseases associated with memory disturbances are important health issues occurring due to a prolonged life span. This article presents the results of a study targeting the emergence of a drug candidate with antiamnesic properties. The effect of berberine (BBR), an isoquinoline alkaloid isolated from the overground parts of Berberis sibirica Pall., on memory and expression of parvalbumin in the mouse hippocampus proper were determined. High-purity BBR was isolated by centrifugal partition chromatography from a methanolic extract from B. sibirica by using a methyl- tert -butyl ether and water (1:1 v / v ) solvent system with 10 mmol/L of triethylamine and hydrochloric acid. In an in vivo study, we assessed the influence of the chronic administration of BBR on different stages of memory-related responses in mice. Our results indicated that the chronic administration of BBR in a higher dose (5 mg/kg) improves long-term memory acquisition in mice, as determined in the passive avoidance test. The hippocampal CA1-CA3 fields showed an increased number of parvalbumin-immunoreactive neurons (PV-IR) and nerve fibers as compared to the control. No significant changes in the dentate gyrus were observed between the groups. The HPLC-ESI-QTOF-MS/MS analysis of the biological material revealed the content of BBR as 363.4 ± 15.0 ng (4.11% of RSD) per brain, 15.06 ± 0.89 ng (5.91% of RSD) per hippocampus, and 54.45 ± 1.40 (4.05% of RSD) ng in 100 µL plasma. The study showed that BBR could be a factor influencing the expression of PV in hippocampal neurons. We speculate that BBR may modulate the level of Ca 2+ in neurons and thus potentially act as a neuroprotective factor against neuronal damages.

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora , on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight ( p < 0.01), amelioration of insulin-sensitivity ( p = 0.021), total cholesterol ( p = 0.014), low-density-lipoprotein-cholesterol ( p < 0.001), alanine-aminotransferase ( p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.

A novel pH-sensitive colorimetric film was prepared based on immobilizing red barberry anthocyanins (RBAs) within composite chitin nanofiber (CNF) and methylcellulose (MC) matrices. The incorporation of CNFs and RBAs improved their mechanical properties, moisture resistance, and UV-vis screening properties. Moreover, the RBAs could be used as colorimetric indicators to detect food spoilage because they are sensitive to changes in pH and ammonia gas production. The RBA-halochromic indicator changed from reddish/crimson → pink → yellow with increasing pH, and from pink → yellow with increasing ammonia vapor concentration. Furthermore, the smart films possessed good antioxidant and antimicrobial activity owing to the presence of the RBAs and CNFs. Finally, the validity of the indicator to monitor the freshness/spoilage of a model food (fish) was demonstrated. Overall, this study shows that active/smart films can be assembled from food grade ingredients that can protect and monitor the freshness of products, like meat and fish., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rheumatoid arthritis (RA) is an autoimmune disease associated with inflammation. In this trial, we aimed to investigate the Immunomodulatory effect of hydroalcoholic extract of black barberry on immune mediators in patients with active rheumatoid arthritis. In this randomized, double-blind, placebo-controlled clinical trial, 80 women with active RA were randomly assigned into two groups of two capsules, each containing 1,000 mg black barberry extract (n = 40) or maltodextrin placebo (n = 40) daily for 12 weeks. Demographic indices, physical activity, dietary intake, and disease activity were investigated using suitable questionnaires. Concentration of cytokines IL-2, IL-4, IL-10, and IL-17 in blood sample were measured using PBMC method. Statistical analysis was performed using SPSS (version 22). At baseline, there were no differences between the two groups in terms of demographic indices, physical activity, and dietary intake (p > .05). Black barberry supplementation reduced the severity of RA. It showed no significant effect on IL-2 and IL-4 cytokines (p > .05). IL-17 levels decreased significantly after the intervention within the black barberry group, while IL-10 had a significant increase in this group (p < .05). Barberry extract may reduce inflammatory and increase anti-inflammatory cytokines in RA, and stimulates the immune response by increasing Th2 production., (© 2020 John Wiley & Sons Ltd.)

Aims: Natural products still serves as a hope for some illnesses which modern medicine fails to cure. Many people, either knowing their effects or not, are using these herbal products. Treatment of chronic heart failure (CHF) is yet a complicated clinical challenge and there is need to improve or make new therapeutic targets. Finding new agents for CHF is an important subject in cardiovascular drug research. In this study, we evaluated the effects of ten herbals on treatment of CHF on isoproterenol-induced model., Methods and Results: Ninety-six male Wistar rats (16 weeks old) were used in 12 groups. Transthoracic echocardiography was performed on the rats for confirmation of CHF model by decreasing ejection fraction. After 4 weeks' treatment, hearts were removed and blood samples were collected in tubes to measure plasma levels of laboratory findings. Our results showed that the mean of ejection fraction in model rats was 51.82 ± 3.49 percent and all of our used natural products could significantly increase the ejection fraction (P < 0.01). The most effective herbals in improving the ejection fraction were Allium sativum (30.69 %), Peganum harmala (26.08 %) and Apium graveolens (24.09 %). The best results in decreasing NT-ProBNP, was obtained from Allium sativum, Peganum harmala and Berberis vulgaris respectively. Our results showed that none of natural products had toxic effect on renal and liver tissues., Conclusion: Our results showed that Allium sativum, Peganum harmala and Berberis vulgaris could significantly improve cardiac function by improvement of left ventricular remodeling, lowering hs-CRP and NT-ProBNP and echocardiographic indexes without liver or renal side effects., (Copyright © 2020. Published by Elsevier Masson SAS.)

Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. However, nephro, hepato, neuro cardio, and hematological toxicities associated with ifosfamide render its use limited. These side effects could range from organ failure to life-threatening situations. The present study aimed to evaluate the attenuating efficiency of Berberis vulgaris root extract (BvRE), a potent nephroprotective, hepatoprotective, and lipid-lowering agent, against ifosfamide-induced toxicities. The study design comprised eight groups of Swiss albino rats to assess different dose regimes of BvRE and ifosfamide. Biochemical analysis of serum (serum albumin, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, and triglycerides) along with complete blood count was performed. Kidney, liver, brain, and heart tissue homogenates were used to find malondialdehyde, catalase, and glutathione S-transferase levels in addition to the acetylcholinesterase of brain tissue. The results were further validated with the help of the histopathology of the selected organs. HeLa cells were used to assess the effect of BvRE on ifosfamide cytotoxicity in MTT assay. The results revealed that pre- and post-treatment regimens of BvRE, as well as the combination therapy exhibited marked protective effects against ifosfamide-induced nephro, hepato, neuro, and cardiotoxicity. Moreover, ifosfamide depicted a synergistic in vitro cytotoxic effect on HeLa cells in the presence of BvRE. These results corroborate that the combination therapy of ifosfamide with BvRE in cancer treatment can potentiate the anticancer effects of ifosfamide along with the amelioration of its conspicuous side effects.

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations., Objective: The present review is focussed to summarize and collect the updated review of information of Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis., Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, antiinflammatory both in vitro and in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A new pH-responsive color indicator film was prepared by blending barberry anthocyanin (BA) with methylcellulose (MC)/chitosan nanofiber (ChNF) composite film. The addition of ChNF and BA increased the mechanical and water barrier properties but reduced the UV-vis light transmittance of the composite film. Anthocyanin showed proper compatibility with the composite film. The color indicator film showed an apparent color change in response to pH changes and ammonia gas, being suitable for indicating the change in food pH, the formation of volatile nitrogen compounds, and food decay. The color indicator film changed clearly from reddish-pink to pale peach and finally to yellow when exposed to different pH buffers. However, in response to ammonia vapor, the color changed from pink to pale green and yellow. Besides, the color indicator film exhibited remarkable antioxidant activity. Therefore, the pH-sensing color indicator film can be used as a smart indicator for real-time freshness monitoring of meat and seafood products., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Magnoflorine (MGN) is a quaternary aporphine alkaloid that exhibits numerous therapeutic properties, including neuropsychopharmacological, anti-anxiety, immunomodulatory, anti-inflammatory, antioxidant, or antifungal activities. The aim of the present study was an investigation of the influence of MGN on viability, proliferation, induction of apoptosis, and cell cycle arrest in NCI-H1299 lung, MDA-MB-468 breast, T98G glioma, and TE671 rhabdomyosarcoma cancer cells. MGN was isolated from the roots of Berberis cretica L. by counter-current partition chromatography (CPC). Cell viability and proliferation assessments were performed by means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and 5-bromo-2'-deoxyuridine (BrDU) assays, respectively. The induction of apoptosis and cell cycle progression was measured using fluorescence-activated cell sorting analysis. MGN in high doses inhibits proliferation, induces apoptosis, and inhibits cell cycle in S/G2 phases in a dose-dependent manner. MGN seems to be a promising anti-cancer compound in therapy of some types of lung, breast, glioma, and rhabdomyosarcoma cancers, for which current standard therapies are limited or have severe strong side effects.

Human liver cancer has emerged as a serious health concern in the world, associated with poorly available therapies. The Berberis genus contains vital medicinal plants with miraculous healing properties and a wide range of bioactivities. In this study, different crude extracts of B. lycium Royle were prepared and screened against Human Hepatocarcinoma (HepG2) cell lines. The water/ethanolic extract of B. lycium Royle (BLE) exhibited significant antiproliferative activity against the HepG2 cancer cell line with an IC 50 value of 47  μ g/mL. The extract decreased the clonogenic potential of HepG2 cells in a dose-dependent manner. It induced apoptotic cell death in HepG2 cells that were confirmed by cytometric analysis and microscopic examination of cellular morphology through DAPI-stained cells. Biochemical evidence of apoptosis came from elevating the intracellular ROS level that was accompanied by the loss of mitochondrial membrane potential. The mechanism of apoptosis was further confirmed by gene expression analysis using RT-qPCR that revealed the decline in Bcl-2 independent of p53 mRNA and a rise in CDK1 while downregulating CDK5, CDK9, and CDK10 mRNA levels at 48 h of BLE treatment. The most active fraction was subjected to HPLC which indicated the presence of berberine (48  μ g/mL) and benzoic acid (15.8  μ g/mL) as major compounds in BLE and a trace amount of luteolin, rutin, and gallic acid. Our study highlighted the importance of the most active BLE extract as an excellent source of nutraceuticals against Human Hepatocarcinoma that can serve as an herbal natural cure against liver cancer., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Kiren Mustafa et al.)

The dried stem bark of Berberis kansuensis C.K.Schneid. (Berberidaceae) was widely used to treat diabetes in traditional Tibetan medicine system. However, its anti-diabetic mechanisms have not been elucidated. In this study, 1 H-NMR-based metabolomics combined with biochemistry assay was applied to investigate the anti-diabetic activities as well as underlying mechanisms of B. kansuensis extract on type 2 diabetic rats. The results showed that after 30 days treatment with B. kansuensis extract, the levels of FBG, GSP, INS, TNF-α, IL-1β and IL-6 were significantly decreased in B. kansuensis group compared with the model group. Besides, a total of 28 metabolites were identified in rat serum by 1 H-NMR-based metabolomics method, 16 of which were significantly different in the normal group compared with the model group, and eight of them were significantly reversed after B. kansuensis intervention. Further analysis of metabolic pathways indicated that therapeutic effect of B. kansuensis might be predominantly related to their ability to improve glycolysis and gluconeogenesis, citric acid cycle, lipid metabolism, amino acid metabolism and choline metabolism. The results of both metabolomics and biochemical analysis indicated that B. kansuensis extract has a potential anti-diabetic effect on type 2 diabetic rats. Its therapeutic effect may be based on the ability of anti-inflammation, alleviating insulin resistance and restoring several disturbed metabolic pathways., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Cancer, even currently, is one of the main reasons for mortality and morbidity, worldwide. In recent years, a great deal of effort has been made to find efficient therapeutic strategies for cancer, however, particularly with regards to side effects and the possibility of complete remission. Berberine (BBR) is a nature-driven phytochemical component originated from different plant groups such as Berberis vulgaris, Berberis aquifolium, and Berberis aristata. BBR is a well-known nutraceutical because of its wide range of pharmacological activities including anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide. In addition, it exhibits inhibitory effects on multiple types of cancers. In this review, we have elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion., (© 2020 International Union of Biochemistry and Molecular Biology.)

Berberis laurina (Berberidaceae) is a well-known medicinal plant used in traditional medicine since ancient times; however, it is scarcely studied to a large-scale fingerprint. This work presents a broad-range fingerprints determination through high-resolution magical angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, a well-established flexible analytical method and one of most powerful "omics" platforms. It had been intended to describe a large range of chemical compositions in all plant parts. Beyond that, HR-MAS NMR allowed the direct investigation of botanical material (leaves, stems, and roots) in their natural, unaltered states, preventing molecular changes. The study revealed 17 metabolites, including caffeic acid, and berberine, a remarkable alkaloid from the genus Berberis L. The metabolic pattern changes of the leaves in the course of time were found to be seasonally dependent, probably due to the variability of seasonal and environmental trends. This metabolites overview is of great importance in understanding plant (bio)chemistry and mediating plant survival and is influenceable by interacting environmental means. Moreover, the study will be helpful in medicinal purposes, health sciences, crop evaluations, and genetic and biotechnological research.

Although Berberis plant species have been advocated as immune modulators, information regarding their mechanism(s) of action is limited. Therefore, in the present study we assessed the efficacy of Berberis lycium Royle fruit extract (BLFE) in the attenuation of lipopolysaccharide (LPS)-induced oxi-inflammatory aggravation and concanavalin A (Con-A)-induced proliferation in murine peritoneal macrophages and lymphocytes, respectively. BLFE strongly suppressed production of the oxidative and inflammatory effector molecules nitric oxide (NO), reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), inflammatory cytokines (TNF-α/IL-6/IL-1β/IFN-γ) as well as chemokines (MCP-1 and RANTES), with a concomitant enhancement in heme oxygenase-1 (HO-1) and IL-10 levels. Subsequent mechanistic analysis revealed that BLFE strongly inhibited the phosphorylation of IκBα as well as MAPKs such as extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun NH2-terminal kinase (JNK), thereby directly resulting in the suppression of nuclear factor-κB (NF-ĸB) and c-Jun activation, ultimately culminating in the observed attenuation of inflammatory molecules. Additionally, BLFE appeared to mitigate Con-A-induced proliferation of Tregs (CD3+ CD4+ CD25+) thereby suggesting its modulatory effects on adaptive immune cells. UPLC-DAD-ESI-QTOF-MS/MS of BLFE revealed the presence of major bioactive phenolics and alkaloids including chlorogenic acid, rutin, catechin and quercetin 3-D-galactoside, berberine and magnoflorine, which could have synergistically contributed to the above findings. Overall, this work provides evidence that BLFE may be effective in the mitigation of inflammatory disorders, especially those associated with NF-κB/MAPK activation.

Berberis lycium (family Berberidaceae) grows in district Sherani, Balochistan, Pakistan. It is used for the treatment of various disorders by the people of Balochistan. The present work was carried out to explore analgesic and neuropharamcological activities of crude methanolic extracts of B. lyceum. The analgesic activity was carried out by acetic acid induced writhing test and formalin test. Open field test, cage crossing test, rearing test, traction test and forced swimming test were carried out in neuropharmacological activities. The results reveal that crude methanolic extracts of B. lyceum showed significant (P&lt;0.05) analgesic activity in acetic acid induced pain as well as with formalin test. In neuropharmacological activities, crude methanolic extracts of B. lyceum showed significant (P&lt;0.05) central nervous system depressant activity and in forced swimming test it showed anxiolytic effects.

Berberis lycium Royle (Berberidaceae) is traditionally used for the treatment of diabetes mellitus. Present study was conducted to determine the antioxidant, antidiabetic and anti-inflammatory effects of aqueous and methanolic whole plant extracts. Total phenolic contents were determined by Folin-ciocalteu method whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl hydrazyl (DPPH) method. In vitro anti-diabetic activity was determined using alpha amylase assay. Acute hypoglycemic activity was investigated on normoglycemic rats. Sub-acute anti-diabetic effects were investigated in alloxan induced diabetic rats for 14 days. Methanolic extract exhibited 183.5±1 mg/g Gallic acid equivalent (GAE) phenolic contents. The methanolic extract exhibited an IC50 of 242µg/mL and 37.26 mg/mL in antioxidant and alpha amylase inhibitory assays respectively. Administration of methanolic extract in normoglycemic rats exhibited significant anti-hyperglycemic effect at 90 and 120 min. Methanolic extract (500 mg/kg extract) significantly reduced blood glucose at day 14. Methanolic extract (500 mg/kg) significantly reduced the concentration of tumor necrosis factor (TNF-α) and interleukin (IL-6) along with reduction in total cholesterol and triglyceride levels in diabetic rats. Administration of methanol extract also improved the hepatic markers. The study suggested that the methanolic extract possessed antidiabetic effect that might be attributed to its alpha amylase, antioxidant and anti-inflammatory potential.

Objective: We performed a meta-analysis to evaluate the efficacy of barberry (Berberis vulgaris L.) supplementation on glycemic indices in adults., Methods: A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and ISI Web of Science from inception up to January 2020, to identify randomized controlled trials (RCTs) investigating the effect of barberry supplementation on glycemic markers including fasting blood sugar (FBS) concentrations, insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and glycosylated hemoglobin (HbA1c) percentage. The results of this meta-analysis were reported, based on the random effects model., Results: In total, 7 studies, comprising 452 participants, were included in the systematic review. The meta-analysis revealed that barberry significantly reduces insulin levels (Hedges's: -0.67; 95% CI: -1.31 to -0.03, P = 0.04, I 2 = 73.3%). However, no considerable changes was observed for FBS levels (WMD: -8.06 mg/dL; 95% CI: -20.46 to 4.33, P = 0.23, I 2 = 96.1%), HbA1c percentage (WMD: -0.83 %; 95% CI: -2.33 to 0.67, P = 0.27, I 2 = 88.3%), and HOMA-IR index (WMD: -0.55; 95% CI: -1.60 to 0.50, P = 0.30, I 2 = 99.4%)., Conclusion: The present study suggests that although barberry supplementation significantly improves insulin levels; however, other glycemic indices might not be affected. However, more high-quality RCTs with longer duration are needed to further clarify the effects of barberry on blood glucose control, especially among patients with diabetes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The ethanolic root extract of Berberis brevissima afforded a new bisbenzylisoquinoline alkaloid, 13-nitrochondrofoline ( 2 ), and two known bisbenzylisoquinoline alkaloids, chondrofoline ( 1 ) and curine ( 4 ). The acetylation of chondrofoline ( 1 ) gave O -acetylchondrofoline ( 3 ). The dimeric structures of 1 and 2 were studied through variable-temperature 1 H NMR spectroscopy at 25, 40, 60, and 80 °C and conformational analysis, using density functional theory employing the M06-2X functional and the 6-31G* basis set. The in vitro antitrypanosomal activity of compounds 1 , 2 , 3 , and 4 against Trypanosoma brucei showed significant potential with MIC values of 2.6, 2.2, 2.3, and 3.8 μM, respectively. Molecular docking evaluation of alkaloids 1 , 2 , 3 , and 4 against known T. brucei protein targets revealed T. brucei phosphodiesterase B1 to be the preferred target. The docking energies of the alkaloids with Tb6PGL (PDB 3EB9) ranged from -88.8 to -106.0 kJ/mol and was comparable to the cocrystallized ligand, citrate ( E dock = -78.3 kJ/mol). It seems reasonable that the curine alkaloids may compete with the natural substrates for these protein targets and serve as leads in designing and developing more potent and selective drugs against T. brucei .

Palmatine (PALM) and berberine (BERB) are widely identified isoquinoline alkaloids among the representatives of the Berberidaceae botanical family. The antiseizure activity of BERB was shown previously in experimental epilepsy models. We assessed the effect of PALM in a pentylenetetrazole (PTZ)-induced seizure assay in zebrafish, with BERB as an active reference compound. Both alkaloids were isolated from the methanolic root extract of Berberis sibirica by counter-current chromatography, and their ability to cross the blood-brain barrier was determined via quantitative structure-activity relationship assay. PALM exerted antiseizure activity, as confirmed by electroencephalographic analysis, and decreased c-fos and bdnf levels in PTZ-treated larvae. In a behavioral assay, PALM dose-dependently decreased PTZ-induced hyperlocomotion. The combination of PALM and BERB in ED 16 doses revealed hyperadditive activity towards PTZ-induced hyperlocomotion. Notably, we have indicated that both alkaloids may exert their anticonvulsant activity through different mechanisms of action. Additionally, the combination of both alkaloids in a 1:2.17 ratio (PALM: BERB) mimicked the activity of the pure extract, which indicates that these two active compounds are responsible for its anticonvulsive activity. In conclusion, our study reveals for the first time the anticonvulsant activity of PALM and suggests the combination of PALM and BERB may have higher therapeutic value than separate usage of these compounds.

Cloud and sediment formation is a major problem in juices and drinks. Barberry juice, as a functional and healthy product, is faced with the sedimentation problem, as an emerging issue. The present study was carried out to identify the sediment forming agents in barberry juice concentrate. The sediment was characterized by a range of different analytical techniques including FTIR, UV spectrophotometry, HPLC and LC-MS analysis. The findings of this research revealed that sugar derived organic acids, which were present in high amounts in barberry juice, were mainly responsible for sedimentation of barberry juice concentrate during cold storage. It was reported that such sugar derived acids with active carboxylic groups could cause instability in products rich in these compounds. The isolated sediment could re-crystalize at different juice concentrations with different shapes and sizes as affected by nucleation and crystal growth rates., (Copyright © 2019 Elsevier Ltd. All rights reserved.)