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Frontiers in Cellular and Infection... 2022With socioeconomic advances and improved living standards, metabolic syndrome has increasingly come into the attention. In recent decades, a growing number of studies... (Review)
Review
With socioeconomic advances and improved living standards, metabolic syndrome has increasingly come into the attention. In recent decades, a growing number of studies have shown that the gut microbiome and its metabolites are closely related to the occurrence and development of many metabolic diseases, and play an important role that cannot be ignored, for instance, obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease and others. The correlation between gut microbiota and metabolic disorder has been widely recognized. Metabolic disorder could cause imbalance in gut microbiota, and disturbance of gut microbiota could aggravate metabolic disorder as well. Berberine (BBR), as a natural ingredient, plays an important role in the treatment of metabolic disorder. Studies have shown that BBR can alleviate the pathological conditions of metabolic disorders, and the mechanism is related to the regulation of gut microbiota: gut microbiota could regulate the absorption and utilization of berberine in the body; meanwhile, the structure and function of gut microbiota also changed after intervention by berberine. Therefore, we summarize relevant mechanism research, including the expressions of nitroreductases-producing bacteria to promote the absorption and utilization of berberine, strengthening intestinal barrier function, ameliorating inflammation regulating bile acid signal pathway and axis of bacteria-gut-brain. The aim of our study is to clarify the therapeutic characteristics of berberine further and provide the theoretical basis for the regulation of metabolic disorder from the perspective of gut microbiota.
Topics: Bacteria; Berberine; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Humans; Non-alcoholic Fatty Liver Disease
PubMed: 36093200
DOI: 10.3389/fcimb.2022.854885 -
Archives of Virology Sep 2020Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a... (Review)
Review
Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a broad range of biological activity, including anticancer, anti-inflammatory and antiviral activity. BBR targets different steps in the viral life cycle and is thus a good candidate for use in novel antiviral drugs and therapies. It has been shown that BBR reduces virus replication and targets specific interactions between the virus and its host. BBR intercalates into DNA and inhibits DNA synthesis and reverse transcriptase activity. It inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodeficiency virus (HIV). This isoquinoline alkaloid has the ability to regulate the MEK-ERK, AMPK/mTOR, and NF-κB signaling pathways, which are necessary for viral replication. Furthermore, it has been reported that BBR supports the host immune response, thus leading to viral clearance. In this short review, we focus on the most recent studies on the antiviral properties of berberine and its derivatives, which might be promising agents to be considered in future studies in the fight against the current pandemic SARS-CoV-2, the virus that causes COVID-19.
Topics: Animals; Antiviral Agents; Berberine; Humans; Plant Extracts; Virus Diseases; Virus Replication; Viruses
PubMed: 32594322
DOI: 10.1007/s00705-020-04706-3 -
Redox Biology Jun 2023Nuclear factor (NF)-κB plays a pivotal role in the regulation of inflammatory response in macrophages. Berberine (BBR), which is an active constituent isolated from...
Nuclear factor (NF)-κB plays a pivotal role in the regulation of inflammatory response in macrophages. Berberine (BBR), which is an active constituent isolated from Coptis rhizome, possesses a prominent anti-inflammatory activity. Here we show that BBR changes the global acetylation landscape in LPS-induced protein acetylation of macrophages and reduces the acetylation of NF-κB subunit p65 at site Lys310(p65), leading to the inhibition of NF-κB translocation and transcriptional activity to suppress the expressions of inflammatory factors. BBR resists the inflammatory response in acute LPS-stimulated mice through downregulation of p65 acetylation in peritoneal macrophages. In obese mice, BBR alleviates the metabolic disorder and inflammation with the reduced acetylation of p65 in white adipose tissue. Furthermore, we demonstrate that BBR acts as a regulator of p65 by inhibiting the expression of p300 in macrophages. Our findings elucidate a new molecular mechanism for the anti-inflammatory effect of BBR via the p300/p65 axis.
Topics: Mice; Animals; NF-kappa B; Berberine; Transcription Factor RelA; Acetylation; Lipopolysaccharides; Macrophages; Anti-Inflammatory Agents
PubMed: 37086629
DOI: 10.1016/j.redox.2023.102704 -
International Journal of Biological... 2023Dietary fat intake is positively associated with elevated risk of colorectal cancer (CRC). Currently, clinical treatments remian inadequate bacause of the complex...
Dietary fat intake is positively associated with elevated risk of colorectal cancer (CRC). Currently, clinical treatments remian inadequate bacause of the complex pathogenesis of CRC induced by a high-fat diet (HFD). Mechanistically, imbalances in gut microbiota are associated with HFD-associated colorectal tumourigenesis. Therefore, we investigated the anti-tumor activity of berberine (BBR) in modulating the dysregulated gut microbiota and related metabolites by preforming 16S rDNA sequencing and liquid chromatography/mass spectrometry. As expected, BBR treatment significantly decreased the number of colonic polyps, ameliorated gut barrier disruption, and inhibited colon inflammation and related oncogenic pathways in AOM/DSS-induced CRC model mice fed with an HFD. Furthermore, BBR alleviated gut microbiota dysbiosis and increased the abundance of beneficial gut microorganisms, including and , in HFD-fed CRC mice. In addition, metabolomics analysis demonstrated significantly altered the glycerophospholipid metabolism during the progression of HFD-associated CRC in mice, whereas BBR treatment reverted these changes in glycerophospholipid metabolites, particularly lysophosphatidylcholine (LPC), which was confirmed to promote CRC cell proliferation and ameliorate cell junction impairment. Notably, BBR had no clear anti-tumor effects on HFD-fed CRC model mice with gut microbiota depletion, whereas transplantation of BBR-treated gut microbiota to gut microbiota-depleted CRC mice recapitulated the inhibitory effects of BBR on colorectal tumourigenesis and LPC levels. This study demonstrated that BBR inhibited HFD-associated CRC directly through modulating gut microbiota-regulated LPC levels, thereby providing a promising microbiota-modulating therapeutic strategy for the clinical prevention and treatment of Western diet-associated CRC.
Topics: Animals; Mice; Berberine; Diet, High-Fat; Lysophosphatidylcholines; Gastrointestinal Microbiome; Colorectal Neoplasms; Carcinogenesis; Mice, Inbred C57BL
PubMed: 37151876
DOI: 10.7150/ijbs.81824 -
BMC Biology Dec 2022Inflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract, and have complications such as colorectal...
BACKGROUND
Inflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract, and have complications such as colorectal cancer and inflammation in other organs. The current treatments for IBDs, which affect 0.3% of the global population, mainly target immune cells and inflammatory cytokines with a success rate of less than 40%.
RESULTS
Here we show that berberine, a natural plant product, is more effective than the frontline drug sulfasalazine in treating DSS (dextran sulfate sodium)-induced colitis in mice, and that berberine not only suppresses macrophage and granulocyte activation but also promotes epithelial restitution by activating Lgr5 intestinal stem cells (ISCs). Mechanistically, berberine increases the expression of Wnt genes in resident mesenchymal stromal cells, an ISC niche, and inhibiting Wnt secretion diminishes the therapeutic effects of berberine. We further show that berberine controls the expression of many circadian rhythm genes in stromal cells, which in turn regulate the expression of Wnt molecules.
CONCLUSIONS
Our findings suggest that berberine acts on the resident stromal cells and ISCs to promote epithelial repair in experimental colitis and that Wnt-β-Catenin signaling may be a potential target for colitis treatment.
Topics: Mice; Animals; Berberine; Dextran Sulfate; Disease Models, Animal; Colitis; Stem Cells; Receptors, G-Protein-Coupled; Inflammation; Intestinal Mucosa
PubMed: 36528592
DOI: 10.1186/s12915-022-01492-z -
Journal of Natural Medicines Mar 2020It has been reported that Sanoshashinto (SanHuangXieXinTang, ), which is composed of Rhei Rhizoma, Scutellariae Radix, and Coptidis Rhizoma, exhibits vasorelaxant...
It has been reported that Sanoshashinto (SanHuangXieXinTang, ), which is composed of Rhei Rhizoma, Scutellariae Radix, and Coptidis Rhizoma, exhibits vasorelaxant effects in vitro and lowers blood pressure of patients. Based on this discovery, in this study, a mixture containing those three materials and combinations of them were extracted with methanol, and the extracts were fractionated into different parts. Effects of all extracts and fractions on high concentration of potassium chloride (High K)- or noradrenaline (NA)-induced contractions of isolated rat aortic rings or helical strips were examined. Qualitative and quantitative HPLC analyses of the extracts and the fractions revealed that the contents of baicalin and berberine in Sanoshashinto methanol extract (SHXXTM) were higher than those of the other constituents. All pharmacological and HPLC data were analyzed by principal component analysis (PCA) software and the results indicated that baicalin, berberine, palmatine, baicalein, and wogonoside contributed significantly to the pharmacological activity. Furthermore, spontaneously hypertensive rats (SHRs) that were orally given SHXXTM or a baicalin-berberine combination showed significantly reduced increase in the rate of systolic blood pressure (SBP) compared to the control group. These findings suggested that Sanoshashinto has significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine, which were the principal constituents of Scutellariae Radix and Coptidis Rhizoma, were the main antihypertensive constituents in Sanoshashinto. It was speculated that baicalin and berberine produced vasorelaxant effects by activating the NO/cGMP pathway and that the BK channel and the DAG/PKC/CPI-17 pathway were also involved.
Topics: Animals; Antihypertensive Agents; Berberine; Blood Pressure; Drugs, Chinese Herbal; Flavonoids; Male; Menthol; Plant Extracts; Principal Component Analysis; Rats
PubMed: 31894475
DOI: 10.1007/s11418-019-01382-9 -
Pharmacological Research Jul 2023A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under...
A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16 S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC values of 4.14 ± 0.35 μM, 26.53 ± 3.12 μM and 11.62 ± 1.44 μM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.
Topics: Animals; Mice; Berberine; Cell Line, Tumor; Gastrointestinal Microbiome; Chromatography, Liquid; Tandem Mass Spectrometry; Hypoxia; Cell Hypoxia; Cell Proliferation; Hypoxia-Inducible Factor 1, alpha Subunit; Gene Expression Regulation, Neoplastic
PubMed: 37315824
DOI: 10.1016/j.phrs.2023.106817 -
Frontiers in Immunology 2022Berberine (BBR), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has a long history of treating dysentery in the clinic. Over the past two decades, the... (Review)
Review
Berberine (BBR), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has a long history of treating dysentery in the clinic. Over the past two decades, the polytrophic, pharmacological, and biochemical properties of BBR have been intensively studied. The key functions of BBR, including anti-inflammation, antibacterial, antioxidant, anti-obesity, and even antitumor, have been discovered. However, the underlying mechanisms of BBR-mediated regulation still need to be explored. Given that BBR is also a natural nutrition supplement, the modulatory effects of BBR on nutritional immune responses have attracted more attention from investigators. In this mini-review, we summarized the latest achievements of BBR on inflammation, gut microbes, macrophage polarization, and immune responses associated with their possible tools in the pathogenesis and therapy of ulcerative colitis and cancer in recent 5 years. We also discuss the therapeutic efficacy and anti-inflammatory actions of BBR to benefit future clinical applications.
Topics: Humans; Anti-Inflammatory Agents; Berberine; Colitis, Ulcerative; Drug Repositioning; Inflammation; Neoplasms; Medicine, Chinese Traditional
PubMed: 36561763
DOI: 10.3389/fimmu.2022.1083788 -
Nature Medicine Dec 2004We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients... (Clinical Trial)
Clinical Trial Comparative Study
We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs.
Topics: Animals; Anticholesteremic Agents; Berberine; Blotting, Northern; China; Cholesterol; Cholesterol, LDL; Cricetinae; DNA Primers; Flow Cytometry; Gene Expression Regulation; Humans; Hypercholesterolemia; Liver; Plasmids; Receptors, LDL; Regulatory Sequences, Nucleic Acid; Reverse Transcriptase Polymerase Chain Reaction; Triglycerides; Tumor Cells, Cultured
PubMed: 15531889
DOI: 10.1038/nm1135 -
Frontiers in Endocrinology 2022Type 2 diabetes mellitus (T2DM) and its complications are major public health problems that seriously affect the quality of human life. The modification of intestinal... (Review)
Review
Type 2 diabetes mellitus (T2DM) and its complications are major public health problems that seriously affect the quality of human life. The modification of intestinal microbiota has been widely recognized for the management of diabetes. The relationship between T2DM, intestinal microbiota, and active ingredient berberine (BBR) in intestinal microbiota was reviewed in this paper. First of all, the richness and functional changes of intestinal microbiota disrupt the intestinal environment through the destruction of the intestinal barrier and fermentation/degradation of pathogenic/protective metabolites, targeting the liver, pancreas, visceral adipose tissue (VAT), etc., to affect intestinal health, blood glucose, and lipids, insulin resistance and inflammation. Then, we focus on BBR, which protects the composition of intestinal microbiota, the changes of intestinal metabolites, and immune regulation disorder of the intestinal environment as the therapeutic mechanism as well as its current clinical trials. Further research can analyze the mechanism network of BBR to exert its therapeutic effect according to its multi-target compound action, to provide a theoretical basis for the use of different phytochemical components alone or in combination to prevent and treat T2DM or other metabolic diseases by regulating intestinal microbiota.
Topics: Humans; Berberine; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Blood Glucose; Insulin Resistance
PubMed: 36465656
DOI: 10.3389/fendo.2022.1074348