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Molecules (Basel, Switzerland) Dec 2021Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer... (Review)
Review
Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial-mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.
Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Berberine; Cell Cycle; Cell Proliferation; Humans; Neoplasms
PubMed: 34885950
DOI: 10.3390/molecules26237368 -
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 -
Nutrients Aug 2022The incidence of Non-Alcoholic Fatty Liver Disease (NAFLD) has been rapidly increasing during the last decade. It is a relevant health problem that affects 25% of the... (Review)
Review
The incidence of Non-Alcoholic Fatty Liver Disease (NAFLD) has been rapidly increasing during the last decade. It is a relevant health problem that affects 25% of the general population. NAFLD involves an extensive array of clinical conditions. So far, no approved pharmacological therapy for NAFLD has been developed. Multiple bioactive compounds have been proposed to treat NAFLD. One of the most promising is Berberine (BBR). Its pleiotropic effect positively impacts various cardiometabolic aspects. In this review, we summarize NAFLD, its metabolic and cardiovascular complications, the hepatoprotective effects of BBR due to its broad spectrum of pharmacological effects, and the potential role of BBR in NAFLD therapy. BBR ameliorates NAFLD by affecting numerous abnormalities. It inhibits lipogenesis and gluconeogenesis, improves insulin resistance and lipid profile, and modulates gut microbiota. The exact mechanism underlying these effects is not yet entirely explained. A growing amount of evidence confirming the positive effects of BBR on multiple metabolic pathways, such as lipids and glucose metabolism, energy homeostasis, or gut microbiota modulation, allows us to speculate about the importance of this natural bioactive substance for NAFLD therapy.
Topics: Berberine; Gluconeogenesis; Humans; Insulin Resistance; Lipogenesis; Liver; Non-alcoholic Fatty Liver Disease
PubMed: 36079717
DOI: 10.3390/nu14173459 -
Nutrients Dec 2021Berberine is a natural alkaloid used to improve glycemia but displays poor bioavailability and increased rates of gastrointestinal distress at higher doses. Recently,... (Randomized Controlled Trial)
Randomized Controlled Trial
Berberine is a natural alkaloid used to improve glycemia but displays poor bioavailability and increased rates of gastrointestinal distress at higher doses. Recently, dihydroberberine has been developed to combat these challenges. This study was designed to determine the rate and extent to which berberine appeared in human plasma after oral ingestion of a 500 mg dose of berberine (B500) or 100 mg and 200 mg doses of dihydroberberine (D100 and D200). In a randomized, double-blind, crossover fashion, five males (26 ± 2.6 years; 184.2 ± 11.6 cm; 91.8 ± 10.1 kg; 17.1 ± 3.5% fat) completed a four-dose supplementation protocol of placebo (PLA), B500, D100, and D200. The day prior to their scheduled visit, participants ingested three separate doses with breakfast, lunch, and dinner. Participants fasted overnight (8-10 h) and consumed their fourth dose with a standardized test meal (30 g glucose solution, 3 slices white bread) after arrival. Venous blood samples were collected 0, 20, 40, 60, 90, and 120 minutes (min) after ingestion and analyzed for BBR, glucose, and insulin. Peak concentration (C) and area under the curve (AUC) were calculated for all variables. Baseline berberine levels were different between groups ( = 0.006), with pairwise comparisons indicating that baseline levels of PLA and B500 were different than D100. Berberine C tended to be different ( = 0.06) between all conditions. Specifically, the observed C for D100 (3.76 ± 1.4 ng/mL) was different than PLA (0.22 ± 0.18 ng/mL, = 0.005) and B500 (0.4 ± 0.17 ng/mL, = 0.005). C for D200 (12.0 ± 10.1 ng/mL) tended ( = 0.06) to be different than B500. No difference in C was found between D100 and D200 ( = 0.11). Significant differences in berberine AUC were found between D100 (284.4 ± 115.9 ng/mL × 120 min) and PLA (20.2 ± 16.2 ng/mL × 120 min, = 0.007) and between D100 and B500 (42.3 ± 17.6 ng/mL × 120 min, = 0.04). Significant differences in D100 BBR AUC (284.4 ± 115.9 ng/mL×120 min) were found between PLA (20.2 ± 16.2 ng/mL × 120 min, = 0.042) and B500 (42.3 ± 17.6 ng/mL × 120 min, = 0.045). Berberine AUC values between D100 and D200 tended ( = 0.073) to be different. No significant differences in the levels of glucose ( = 0.97) and insulin ( = 0.24) were observed across the study protocol. These results provide preliminary evidence that four doses of a 100 mg dose of dihydroberberine and 200 mg dose of dihydroberberine produce significantly greater concentrations of plasma berberine across of two-hour measurement window when compared to a 500 mg dose of berberine or a placebo. The lack of observed changes in glucose and insulin were likely due to the short duration of supplementation and insulin responsive nature of study participants. Follow-up efficacy studies on glucose and insulin changes should be completed to assess the impact of berberine and dihydroberberine supplementation in overweight, glucose intolerant populations.
Topics: Adolescent; Adult; Area Under Curve; Berberine; Biological Availability; Blood Glucose; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Gastrointestinal Absorption; Healthy Volunteers; Humans; Insulin; Kinetics; Male; Meals; Middle Aged; Pilot Projects; Postprandial Period; Young Adult
PubMed: 35010998
DOI: 10.3390/nu14010124 -
Biomedicine & Pharmacotherapy =... Jan 2021The increased incidence of metabolic diseases (e.g., diabetes and obesity) has seriously affected human health and life safety worldwide. It is of great significance to... (Review)
Review
The increased incidence of metabolic diseases (e.g., diabetes and obesity) has seriously affected human health and life safety worldwide. It is of great significance to find effective drugs from natural compounds to treat metabolic diseases. Berberine (BBR), an important quaternary benzylisoquinoline alkaloid, exists in many traditional medicinal plants. In recent years, BBR has received widespread attention due to its good potential in the treatment of metabolic diseases. In order to promote the basic research and clinical application of BBR, this review provides a timely and comprehensive summary of the pharmacological and clinical advances of BBR in the treatment of five metabolic diseases, including type 2 diabetes mellitus, obesity, non-alcoholic fatty liver disease, hyperlipidemia, and gout. Both animal and clinical studies have proved that BBR has good therapeutic effects on these five metabolic diseases. The therapeutic effects of BBR are based on regulating various metabolic aspects and pathophysiological procedures. For example, it can promote insulin secretion, improve insulin resistance, inhibit lipogenesis, alleviate adipose tissue fibrosis, reduce hepatic steatosis, and improve gut microbiota disorders. Collectively, BBR may be a good and promising drug candidate for the treatment of metabolic diseases. More studies, especially clinical trials, are needed to further confirm its molecular mechanisms and targets. In addition, large-scale, long-term and multi-center clinical trials are necessary to evaluate the efficacy and safety of BBR in the treatment of these metabolic diseases.
Topics: Animals; Berberine; Biological Availability; Energy Metabolism; Humans; Metabolic Diseases; Signal Transduction; Treatment Outcome
PubMed: 33186794
DOI: 10.1016/j.biopha.2020.110984 -
Theranostics 2019Elevated levels of plasma free fatty acid (FFA) and disturbed mitochondrial dynamics play crucial roles in the pathogenesis of diabetic kidney disease (DKD). However,...
Elevated levels of plasma free fatty acid (FFA) and disturbed mitochondrial dynamics play crucial roles in the pathogenesis of diabetic kidney disease (DKD). However, the mechanisms by which FFA leads to mitochondrial damage in glomerular podocytes of DKD and the effects of Berberine (BBR) on podocytes are not fully understood. : Using the db/db diabetic mice model and cultured mouse podocytes, we investigated the molecular mechanism of FFA-induced disturbance of mitochondrial dynamics in podocytes and testified the effects of BBR on regulating mitochondrial dysfunction, podocyte apoptosis and glomerulopathy in the progression of DKD. : Intragastric administration of BBR for 8 weeks in db/db mice significantly reversed glucose and lipid metabolism disorders, podocyte damage, basement membrane thickening, mesangial expansion and glomerulosclerosis. BBR strongly inhibited podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation and dysfunction both and . Mechanistically, BBR could stabilize mitochondrial morphology in podocytes via abolishing palmitic acid (PA)-induced activation of dynamin-related protein 1 (Drp1). : Our study demonstrated for the first time that BBR may have a previously unrecognized role in protecting glomerulus and podocytes via positively regulating Drp1-mediated mitochondrial dynamics. It might serve as a novel therapeutic drug for the treatment of DKD.
Topics: Animals; Apoptosis; Berberine; Cells, Cultured; Diabetic Nephropathies; Dynamins; Fatty Acids; Mice; Mice, Inbred NOD; Mitochondria; Mitochondrial Dynamics; Podocytes; Treatment Outcome
PubMed: 31037132
DOI: 10.7150/thno.30640 -
Biological Research Jul 2019Berberine (BBR), a compound extracted from a variety of medicinal herbs, has been shown multiple pharmacological effects against cancer cells of different origins....
BACKGROUND
Berberine (BBR), a compound extracted from a variety of medicinal herbs, has been shown multiple pharmacological effects against cancer cells of different origins. Cisplatin (DDP) is known as an effective chemotherapeutic agent against cancer by inducing DNA damage and cell apoptosis. However, the effect of the combined used of BBR and DDP on cell necroptosis in ovarian cancer has not been reported.
METHODS
OVCAR3 and three patient-derived primary ovarian cancer cell lines (POCCLs) were chosen as the experimental objects. To determine the potential anti-cancer activity of BBR and DDP in combination, we firstly treated OVCAR3 and POCCLs cells with BBR and/or DDP. The cell viability of OVCAR3 and POCCLs with treatment of BBR or DDP for different hours was measured by CCK-8 assay. Flow cytometry was used to analyze cell cycle distribution and changes in apoptotic cells after treatment with BBR and/or DDP. The morphological changes of OVCAR3 cells were observed by using Transmission electron microscopy (TEM) analysis. Proliferation, apoptosis and necroptosis related markers of OVCAR3 and POCCLs with treatment of BBR or DDP were measured by RT-qPCR, western blotting and immunofluorescence assay.
RESULTS
Our results demonstrated that BBR significantly inhibited the proliferation of OVCAR3 and primary ovarian cancer cells in a dose- and time-dependent manner. The combination treatment of BBR and DDP had a prominent inhibitory effect on cancer cell growth and induced G0/G1 cell cycle arrest. TEM revealed that the majority of cells after BBR or DDP treatment had an increasing tendency of typical apoptotic and necrotic cell death morphology. Besides, BBR and DDP inhibited the expression of PCNA and Ki67 and enhanced the expression and activation of Caspase-3, Caspase-8, RIPK3 and MLKL.
CONCLUSION
This study proposed that the combination therapy of BBR and DDP markedly enhanced more ovarian cancer cell death by inducing apoptosis and necroptosis, which may improve the anticancer effect of chemotherapy drugs. The apoptosis involved the caspase-dependent pathway, while the necroptosis involved the activation of the RIPK3-MLKL pathway. We hope our findings might provide a new insight for the potential of BBR as a therapeutic agent in the treatment of ovarian cancer.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Berberine; Caspases; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Female; Humans; Necrosis; Ovarian Neoplasms
PubMed: 31319879
DOI: 10.1186/s40659-019-0243-6 -
Aging Cell Jan 2020Although aging and senescence have been extensively studied in the past few decades, however, there is lack of clinical treatment available for anti-aging. This study...
Although aging and senescence have been extensively studied in the past few decades, however, there is lack of clinical treatment available for anti-aging. This study presents the effects of berberine (BBR) on the aging process resulting in a promising extension of lifespan in model organisms. BBR extended the replicative lifespan, improved the morphology, and boosted rejuvenation markers of replicative senescence in human fetal lung diploid fibroblasts (2BS and WI38). BBR also rescued senescent cells with late population doubling (PD). Furthermore, the senescence-associated β-galactosidase (SA-β-gal)-positive cell rates of late PD cells grown in the BBR-containing medium were ~72% lower than those of control cells, and its morphology resembled that of young cells. Mechanistically, BBR improved cell growth and proliferation by promoting entry of cell cycles from the G or G phase to S/G -M phase. Most importantly, BBR extended the lifespan of chemotherapy-treated mice and naturally aged mice by ~52% and ~16.49%, respectively. The residual lifespan of the naturally aged mice was extended by 80%, from 85.5 days to 154 days. The oral administration of BBR in mice resulted in significantly improved health span, fur density, and behavioral activity. Therefore, BBR may be an ideal candidate for the development of an anti-aging medicine.
Topics: Animals; Berberine; Cellular Senescence; Cyclins; Genes, p16; Humans; Male; Medicine, Chinese Traditional; Mice
PubMed: 31773901
DOI: 10.1111/acel.13060 -
Genomics, Proteomics & Bioinformatics Dec 2020Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes...
Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes mellitus. However, the main limitation of its wider application is ingredient complexity of this formula. Thus, it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action. Here, we compared the effects of GQD and berberine, a hypothetical key active pharmaceutical ingredient of GQD, on a diabetic rat model by comprehensive analyses of gut microbiota, short-chain fatty acids, proinflammatory cytokines, and ileum transcriptomics. Our results show that berberine and GQD had similar effects on lowering blood glucose levels, modulating gut microbiota, inducing ileal gene expression, as well as relieving systemic and local inflammation. As expected, both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria, including Faecalibacterium and Roseburia, thereby attenuating intestinal inflammation and lowering glucose. Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD. Moreover, concentration of serum proinflammatory cytokines and expression of immune-related genes, including Nfkb1, Stat1, and Ifnrg1, in pancreatic islets were significantly reduced after treatment. Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota. The strategy employed would facilitate further standardization and widespread application of TCM in many diseases.
Topics: Animals; Berberine; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Gastrointestinal Microbiome; Hypoglycemic Agents; Rats
PubMed: 33359679
DOI: 10.1016/j.gpb.2019.09.007 -
Oxidative Medicine and Cellular... 2021is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of , has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta-analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM.
METHODS
Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2-hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), along with inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine.
RESULTS
Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c (MD = -0.73; 95% CI (-0.97, -0.51)), FPG (MD = -0.86, 95% CI (-1.10, -0.62)), and 2hPG (MD = -1.26, 95% CI (-1.64, -0.89)). Improved insulin resistance was assessed by lowering FINS (MD = -2.05, 95% CI (-2.62, -1.48)), HOMA-IR (MD = -0.71, 95% CI (-1.03, -0.39)), and BMI (MD = -1.07, 95% CI (-1.76, -0.37)). Lipid metabolisms were also ameliorated via the reduction of TG (MD = -0.5, 95% CI (-0.61, -0.39)), TC (MD = 0.64, 95% CI (-0.78, -0.49)), and LDL (MD = 0.86, 95% CI (-1.06, -0.65)) and the upregulation of HDL (MD = 0.17, 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor.
CONCLUSION
There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.
Topics: Berberine; Diabetes Mellitus, Type 2; Humans; Randomized Controlled Trials as Topic
PubMed: 34956436
DOI: 10.1155/2021/2074610