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Frontiers in Cellular and Infection... 2020The gastrointestinal microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of several diseases. Berberine has... (Review)
Review
The gastrointestinal microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of several diseases. Berberine has been used to treat obesity, diabetes mellitus, atherosclerosis, and metabolic diseases in China. There are also clinical trials regarding berberine use in cardiovascular, gastrointestinal, and endocrine diseases. Berberine elicits clinical benefits at standard doses and has low toxicity. The mechanism underlying the role of berberine in lipid-lowering and insulin resistance is incompletely understood, but one of the possible mechanisms is related to its effect on the gastrointestinal microbiota. An extensive search in electronic databases (PubMed, Scopus, Embase, Web of Sciences, Science Direct) was used to identify the role of the gastrointestinal microbiota in the berberine treatment. The aim of this review was to summarize the pharmacologic effects of berberine on animals and humans by regulation of the gastrointestinal microbiota.
Topics: Animals; Atherosclerosis; Berberine; China; Gastrointestinal Microbiome; Humans; Insulin Resistance
PubMed: 33680978
DOI: 10.3389/fcimb.2020.588517 -
Toxins Nov 2020Berberine is a plant metabolite belonging to the group of isoquinoline alkaloids with strong biological and pharmacological activity. Currently, berberine is receiving... (Review)
Review
Berberine is a plant metabolite belonging to the group of isoquinoline alkaloids with strong biological and pharmacological activity. Currently, berberine is receiving considerable interest due to its anticancer activity based on many biochemical pathways, especially its proapoptotic and anti-inflammatory activity. Therefore, the growing number of papers on berberine demands summarizing the knowledge and research trends. The efficacy of berberine in breast and colon cancers seems to be the most promising aspect. Many papers focus on novel therapeutic strategies based on new formulations or search for new active derivatives. The activity of berberine is very important as regards sensitization and support of anticancer therapy in combination with well-known but in some cases inefficient therapeutics. Currently, the compound is being assessed in many important clinical trials and is one of the most promising and intensively examined natural agents.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Berberine; Cardiovascular Diseases; Drug Resistance; Humans; Mental Disorders; Metabolic Diseases; Neurodegenerative Diseases; Protective Agents
PubMed: 33198257
DOI: 10.3390/toxins12110713 -
Biomedicine & Pharmacotherapy =... Jul 2020This study provides a critical overview of experimental studies in vitro, in humans, and in animals that evaluated the efficacy of Berberine and its effect on management...
This study provides a critical overview of experimental studies in vitro, in humans, and in animals that evaluated the efficacy of Berberine and its effect on management of obesity and the related metabolic consequences. As a result of this review, we summarized the effects of Berberine in different models and the related mechanism of actions. In preclinical models, Berberine demonstrates that it affects gut microbiota by reducing diversity of microbes starting at a dosage of 100 mg/kg/day. Moreover, in animal models, Berberine explicates an action on glucose through the inhibition of α-glycosidase at a dose of 200 mh/kg/day. Berberine is also known to be effective against differentiation of adipocytes through a decrease in LXRs, PPARs, and SREBPs expression at 150 mg/kg/day. Other mechanism ascribed to Berberine are related to its inhibition of hepatic gluconeogenesis through the Phospheoenolpyruvate carboxykinase (PEPCK), Glucose-6-phosphate (G6Pase) and AMP-activated protein kinase (AMPK). Furthermore, Berberine (associated to Red Yeast Rice) is effective in decreasing lipid levels in rats, which consequently lowers the change of weight gain at dosage of 40 mg/kg to 380 mg/kg/day. All the above preclinical data are confirmed in human studies where Berberine can modulate the diversity of gut microbes at the dose of 500 mg/day. In addition, Berberine is found to have a beneficial impact on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans, an amelioration on glucose accumulation at 1.0 g daily dose was also observed. For all these reasons, this review gives an important good account of the impact of Berberine in obesity treatment and prevention.
Topics: Adipocytes; Berberine; Blood Glucose; Cholesterol; Gastrointestinal Microbiome; Gluconeogenesis; Humans; Insulin Resistance; Obesity; Weight Loss
PubMed: 32353823
DOI: 10.1016/j.biopha.2020.110137 -
Cell Cycle (Georgetown, Tex.) Nov 2022Sepsis is a systemic inflammatory condition caused by an unbalanced immunological response to infection, which affects numerous organs, including the intestines.... (Review)
Review
Sepsis is a systemic inflammatory condition caused by an unbalanced immunological response to infection, which affects numerous organs, including the intestines. Lipopolysaccharide (LPS; also known as endotoxin), a substance found in Gram-negative bacteria, plays a major role in sepsis and is mostly responsible for the disease's morbidity and mortality. Berberine is an isoquinoline alkaloid found in a variety of plant species that has anti-inflammatory properties. For many years, berberine has been used to treat intestinal inflammation and infection. Berberine has been reported to reduce LPS-induced intestinal damage. The potential pathways through which berberine protects against LPS-induced intestinal damage by inhibiting NF-κB, suppressing MAPK, modulating ApoM/S1P pathway, inhibiting COX-2, modulating Wnt/Beta-Catenin signaling pathway, and/or increasing ZIP14 expression are reviewed. LPS, lipopolysaccharide; TLR, Toll-like receptor; MD-2, myeloid differentiation factor 2; CD14, cluster of differentiation 14; LBP, lipopolysaccharide-binding protein; MYD88, myeloid differentiation primary response 88; NF-κB, nuclear factor kappa light-chain enhancer of activated B cells; MAPK, mitogen-activated protein kinase; IL, interleukin; TNFα, tumor necrosis factor-alpha; Caco-2, cyanocobalamin uptake by human colon adenocarcinoma cell line; MLCK, myosin light-chain kinase; TJ, tight junction; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; IBS, irritable bowel syndrome; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase (JNK; GVB, gut-vascular barrier; ApoM, apolipoprotein M; S1P, sphingosine-1-phosphate; VE-cadherin, vascular endothelial cadherin; AJ, adherens junction; PV1, plasmalemma vesicle-associated protein-1; HDL, high-density lipoprotein; Wnt, wingless-related integration site; Fzd, 7-span transmembrane protein Frizzled; LRP, low-density lipoprotein receptor-related protein; TEER, transendothelial/transepithelial electrical resistance; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; ZIP, Zrt-Irt-like protein; PPAR, peroxisome proliferator-activated receptors; p-PPAR, phosphorylated-peroxisome proliferator-activated receptors; ATF, activating transcription factors; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; SARA, subacute ruminal acidosis; IPEC-J2, porcine intestinal epithelial cells; ALI, acute lung injury; ARDS, acute respiratory distress syndrome.
Topics: Humans; Swine; Animals; Lipopolysaccharides; Berberine; NF-kappa B; Peroxisome Proliferator-Activated Receptors; Caco-2 Cells; Cyclooxygenase 2; Adenocarcinoma; Colonic Neoplasms; Sepsis; Intestines; Somatomedins
PubMed: 35852392
DOI: 10.1080/15384101.2022.2100682 -
Nature Communications Oct 2020Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a... (Randomized Controlled Trial)
Randomized Controlled Trial
Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).
Topics: Berberine; Diabetes Mellitus, Type 2; Female; Gastrointestinal Microbiome; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metagenome; Middle Aged; Placebos; Probiotics; Treatment Outcome
PubMed: 33024120
DOI: 10.1038/s41467-020-18414-8 -
Molecules (Basel, Switzerland) Jul 2022Cancer has been a serious public health problem. Berberine is a famous natural compound from medicinal herbs and shows many bioactivities, such as antioxidant,... (Review)
Review
Cancer has been a serious public health problem. Berberine is a famous natural compound from medicinal herbs and shows many bioactivities, such as antioxidant, anti-inflammatory, antidiabetic, anti-obesity, and antimicrobial activities. In addition, berberine shows anticancer effects on a variety of cancers, such as breast, lung, gastric, liver, colorectal, ovarian, cervical, and prostate cancers. The underlying mechanisms of action include inhibiting cancer cell proliferation, suppressing metastasis, inducing apoptosis, activating autophagy, regulating gut microbiota, and improving the effects of anticancer drugs. This paper summarizes effectiveness and mechanisms of berberine on different cancers and highlights the mechanisms of action. In addition, the nanotechnologies to improve bioavailability of berberine are included. Moreover, the side effects of berberine are also discussed. This paper is helpful for the prevention and treatment of cancers using berberine.
Topics: Antineoplastic Agents; Berberine; Gastrointestinal Microbiome; Humans; Male; Obesity; Plants, Medicinal
PubMed: 35889396
DOI: 10.3390/molecules27144523 -
Molecules (Basel, Switzerland) Dec 2022The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes.... (Review)
Review
The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes. Pancreatitis is characterized by inflammation of the pancreas leading to temporary or permanent pancreatic dysfunction. Inflammation and fibrosis caused by chronic pancreatitis exacerbate malignant transformation and significantly increase the risk of developing pancreatic cancer, the world's most aggressive cancer with a 5-year survival rate less than 10%. Berberine (BBR) is a naturally occurring plant-derived polyphenol present in a variety of herbal remedies used in traditional medicine to treat ulcers, infections, jaundice, and inflammation. The current review summarizes the existing in vitro and in vivo evidence on the effects of BBR against pancreatitis and pancreatic cancer with a focus on the signalling mechanisms underlying the effects of BBR.
Topics: Humans; Berberine; Pancreatitis; Pancreas; Pancreatic Neoplasms; Inflammation
PubMed: 36500723
DOI: 10.3390/molecules27238630 -
Reproductive Health Aug 2021Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis.
BACKGROUND
Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS.
METHODS
We identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed.
RESULTS
Twenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Myo-inositol + D-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: - 0.72 [95% CI (- 1.11)-(- 0.34)] to - 0.89 [95% CI (- 1.460)-(- 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events.
CONCLUSIONS
Ours is the first study to report that for women with PCOS, myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with D-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524.
Topics: Berberine; Clinical Decision-Making; Female; Humans; Hypoglycemic Agents; Inositol; Insulin; Insulin Resistance; Metabolome; Metformin; Network Meta-Analysis; Polycystic Ovary Syndrome; Thiazolidinediones; Uncertainty
PubMed: 34407851
DOI: 10.1186/s12978-021-01207-7 -
International Journal of Biological... 2022Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, and it has become one of the world-recognized medical problems as it is recurrent...
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, and it has become one of the world-recognized medical problems as it is recurrent and refractory. Berberine (BBR) is an effective drug for UC treatment. However, the underlying mechanism and targets remain obscure. In this study, we systematically investigated the therapeutic effect and its mechanism of BBR in ameliorating DSS-induced mouse colitis. Expectedly, the colon inflammation was significantly relieved by BBR, and microbiota depletion by antibiotic cocktail significantly reversed the therapeutic effect. Further studies showed that BBR can regulate the abundance and component of bacteria, reestablish the broken chemical and epithelial barriers. Meanwhile, BBR administration dramatically decreased ILC1 and Th17 cells, and increased Tregs as well as ILC3 in colonic tissue of DSS-induced mice, and it was able to regulate the expression of various immune factors at the mRNA level. Moreover, a proteomic study revealed that Wnt/β-catenin pathway was remarkably enhanced in colonic tissue of BBR-treated mice, and the therapeutic effect of BBR was disappeared after the intervention of Wnt pathway inhibitor FH535. These results substantially revealed that BBR restores DSS-induced colon inflammation in a microbiota-dependent manner, and BBR performs its protective roles in colon by maintaining the structure and function of the intestinal mucosal barrier, regulating the intestinal mucosal immune homeostasis and it works through the Wnt/β-catenin pathway. Importantly, these findings also provided the proof that BBR serves as a potential gut microbiota modulator and mucosal barrier protector for UC prevention and therapy.
Topics: Animals; Berberine; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Intestinal Mucosa; Mice; Proteomics; Wnt Signaling Pathway; beta Catenin
PubMed: 35280677
DOI: 10.7150/ijbs.65476 -
Journal of Translational Medicine Sep 2022Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR...
BACKGROUND
Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology.
METHODS
HLP hamster model was induced by high-fat diet. Hematoxylin-eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology.
RESULTS
The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP.
CONCLUSIONS
In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.
Topics: Animals; Berberine; Cricetinae; Humans; Hyperlipidemias; Lipidomics; Lipids; Network Pharmacology
PubMed: 36076294
DOI: 10.1186/s12967-022-03623-0