The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, emerging as a significant health issue on a global scale. Berberine exhibits potential for treating NAFLD, but clinical evidence remains inconclusive. This meta-analysis was conducted to assess the efficacy and safety of berberine for treating NAFLD. METHODS: This study was registered with PROSPERO (No. CRD42023462338). Identification of randomized controlled trials (RCTs) involved searching 6 databases covering the period from their initiation to 9 September 2023. The primary outcomes comprised liver function markers such as glutamyl transpeptidase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), lipid indices including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment for insulin resistance (HOMA-IR) and body mass index (BMI). Review Manager 5.4 and STATA 17.0 were applied for analysis. RESULTS: Among 10 RCTs involving 811 patients, berberine demonstrated significant reductions in various parameters: ALT (standardized mean difference (SMD) = - 0.72), 95% confidence interval (Cl) [- 1.01, - 0.44], P < 0.00001), AST (SMD = - 0.79, 95% CI [- 1.17, - 0.40], P < 0.0001), GGT (SMD = - 0.62, 95% CI [- 0.95, - 0.29], P = 0.0002), TG (SMD = - 0.59, 95% CI [- 0.86, - 0.31], P < 0.0001), TC(SMD = - 0.74, 95% CI [- 1.00, - 0.49], P < 0.00001), LDL-C (SMD = - 0.53, 95% CI [- 0.88, - 0.18], P = 0.003), HDL-C (SMD = - 0.51, 95% CI [- 0.12, 1.15], P = 0.11), HOMA-IR (SMD = - 1.56, 95% CI [- 2.54, - 0.58], P = 0.002), and BMI (SMD = - 0.58, 95% CI [- 0.77, - 0.38], P < 0.00001). Importantly, Berberine exhibited a favorable safety profile, with only mild gastrointestinal adverse events reported. CONCLUSION: This meta-analysis demonstrates berberine's efficacy in improving liver enzymes, lipid profile, and insulin sensitivity in NAFLD patients. These results indicate that berberine shows promise as an adjunct therapy for NAFLD. Trial registration The protocol was registered with PROSPERO (No. CRD42023462338). Registered on September 27, 2023.

Oral treatment with Berberine reduces peripheral nociception: Possible interaction with different nociceptive pathways activated by different allogeneic substances.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine was identified in extracts of Berberis ruscifolia Lam., a plant used in traditional medicine as an analgesic. Its presence may be involved in the reported pharmacological activity of this species. However, there is still a lack of scientific research concerning its analgesic activity in the peripheral nervous system. AIM OF THE STUDY: To investigate Berb-induced antinociception in the formalin test and to evaluate several pathways related to its pharmacological antinociceptive effects in chemical models of nociception in mice. MATERIALS AND METHODS: The antinociceptive activity of Berb was assessed by inducing the paw licking in mice with different allodynic agents. In the formalin test, the antiedematous and antithermal effect of Berb was evaluated simultaneously in the same experiment. Other nociceptive behavior produced by endogenous [prostaglandin E2 (PGE2), histamine (His), glutamate (Glu) or bradykinin (BK)] or exogenous [capsaicin (Caps) and cinnamaldehyde (Cin)] chemical stimuli, and activators as protein kinase A (PKA) and C (PKC), were also evaluated.The in vivo doses for p.o. were 3 and 30 mg/kg. RESULTS: Berb, at 30 mg/kg p.o., showed a significant inhibition of the nociceptive action in formalin in both phases being stronger at the inflammatory phase (59 ± 9%) and more active than Asp (positive control) considering the doses evaluated. Moreover, Berb inhibited the edema (34 ± 10%), but not the temperature in the formalin test. Regarding the different nociceptive signaling pathways evaluated, the most relevant data were that the administration of p.o. of Berb, at 30 mg/kg, caused significant inhibition of nociception induced by endogenous [His (72 ± 11%), PGE2 (78 ± 4%), and BK (51 ± 7%)], exogenous [Cap (68 ± 4%) and Cinn (57 ± 5%)] compounds, and activators of the PKA [(FSK (86 ± 3%)] and PKC [(PMA(86 ± 6%)] signaling pathway. Berb did not inhibit the nociceptive effect produced by Glu. CONCLUSION: The present study demonstrated, for the first time, the potential of Berb in several nociceptive tests, with the compound present in B. ruscifolia contributing to the analgesic effect reported for this species.

Efficacy and safety of berberine for premature ventricular contractions: a meta-analysis and systematic review of randomized controlled trials.

CONTEXT: Berberine is a potential drug that can effectively treat cardiovascular diseases, including premature ventricular contractions (PVCs). OBJECTIVE: This study was conducted to assess the efficacy and safety of berberine for PVCs. METHODS: The literature was searched using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang, and Chinese Biomedical Literature Database (CBM) for randomized controlled trials (RCTs) from inception to October 1, 2022. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to assess the quality of evidence. RESULTS: Ten RCTs with 896 participants were included in the meta-analysis. The results showed that compared to antiarrhythmic drugs (AD), berberine (BE) combined with AD had a higher effective rate (RR = 1.26; 95% CI:1.12, 1.42; p = 0.0001) with no significant incidence of adverse reactions (RR = 0.93; 95% CI:0.33, 2.57; p = 0.88), and BE alone had no significant difference in effective rate (RR = 0.91; 95% CI:0.77, 1.07; p = 0.23), and a lower incidence of adverse reactions (RR = 0.38; 95% CI:0.15, 0.97; p = 0.04) and recurrence rate (RR = 0.40; 95% CI:0.18, 0.88; p = 0.02). CONCLUSIONS: The results suggest that BE is an effective and safe adjunctive method for PVCs. In addition, BE is recommended for patients with PVCs who had severe adverse reactions after administrating AD as an alternative therapy.

Pilot study on the efficacy and safety of berberine in people with metabolic syndrome and human immunodeficiency virus infection.

BACKGROUND: Antiretroviral therapy has increased the life expectancy of people living with HIV. However, this increase is not free of comorbidities, and metabolic syndrome is one of the most prevalent. Berberine is an alkaloid nutraceutical that has been shown to ameliorate metabolic disorders such as prediabetes, polycystic ovary syndrome, and non-alcoholic fatty liver disease. However, it has not been tested in HIV infection. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of berberine in improving metabolic syndrome. METHODS AND RESULTS: In this double-blind, placebo-controlled trial, adults living with HIV under virological suppression and metabolic syndrome received either berberine 500 mg TID or placebo for 20 weeks. The primary outcomes were a composite of weight reduction, insulin resistance decrease, and lipid profile improvement. A total of 43 participants were randomized (22 in the berberine group and 21 in the placebo group); 36 participants completed the follow-up and were analyzed. The berberine group showed a reduction in weight and body mass index, lower insulin resistance, and a reduction in TNF-alpha. The control group had higher total cholesterol, c-LDL, and IL-6 concentration. CONCLUSION: In people living with HIV under virological suppression, berberine was safe and improves clinical and biochemical components of metabolic syndrome. However, further studies with more participants and longer intervention periods need to be explored.

Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: Berberine is a nutraceutical that can improve lipid metabolism. Berberine may also affect sex hormones and exert sex-specific lipid-modifying effects, which have been overlooked. This study aimed to comprehensively review the efficacy and safety of berberine in adults for the treatment of dyslipidemia with consideration of potential sex disparity. Data Sources We searched Medline, Embase, Wanfang, CNKI, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to 13 December 2022. No language restrictions were applied. This study was registered in PROSPERO (CRD42021293218) prior to completing the literature search. Study Selection Two blinded reviewers assessed studies for inclusion. Eligible studies were randomized controlled trials in adults that compared berberine versus placebo, and measured blood lipids or lipoproteins. Data Extraction and Synthesis Data extraction was performed by two blinded reviewers using a structured form in Covidence. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials. Mean differences (MD) were estimated using inverse variance weighting with random effects models for lipid outcomes using R. Adverse events (AEs) were described narratively. Main Outcomes Primary outcomes were low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein B. Secondary outcomes were gastrointestinal and muscle-related AEs. RESULTS: Eighteen studies (n = 1788 participants), conducted mainly in mainland China and Hong Kong (15 studies [83%]), were included with treatment durations ranging from 4 to 24 weeks. Berberine reduced LDL cholesterol (- 0.46 mmol/L, 95% CI - 0.62 to - 0.30, 14 studies, n = 1447), total cholesterol (- 0.48 mmol/L, 95% CI - 0.63 to - 0.33, 17 studies, n = 1637), triglycerides (- 0.34 mmol/L, 95% CI - 0.46 to - 0.23, 18 studies, n = 1661) and apolipoprotein B (- 0.25 g/L, 95% CI - 0.40 to - 0.11, 2 studies, n = 127). Berberine increased HDL cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.11, 15 studies, n = 1471). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (- 0.07 mmol/L, 95% CI - 0.16 to 0.02). Among 16 studies that reported AEs, no serious AEs were reported for berberine. Gastrointestinal AEs were reported in 12 studies and tended to be more frequent in participants allocated to berberine versus placebo (2-23% vs 2-15%). CONCLUSIONS: Berberine produces small reductions in LDL cholesterol, triglycerides, and apolipoprotein B, with potential sex-specific effects on HDL cholesterol. Large-scale trials that consider sex disparity and assess clinical outcomes are required.

Berberine is found naturally in barberry and goldenthread, plants which have long been used in traditional herbal medicine in Asia. Nowadays berberine is used as a purified product and is easy to purchase as a nutraceutical supplement or non-prescription drug. People with dyslipidemia, a medical condition often known as 'high cholesterol', may prefer treatment with a nutraceutical such as berberine to reduce blood cholesterol. In recent years, many studies have contrasted the effects of taking berberine with an inactive placebo. This study aimed to combine all the available randomized controlled trials that assessed berberine's effects on blood lipids and lipoproteins. We included 18 studies that used berberine doses of 900­1500 mg/day, the majority of which were conducted in mainland China and Hong Kong. We found that on average berberine can modestly reduce low-density lipoprotein (LDL) cholesterol by 0.5 mmol/L (18 mg/dL) and triglycerides by 0.3 mmol/L (30 mg/dL). Berberine also increases high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (2 mg/dL). Interestingly, women may obtain a greater increase in HDL cholesterol than men. The short-term use of berberine appears to be safe. No study participants treated with berberine experienced a serious adverse event. However, berberine may occasionally cause constipation, diarrhea, or nausea. Larger high-quality studies are still needed to determine the long-term effects of berberine for dyslipidemia.

Berberine and health outcomes: An umbrella review.

Berberine is a plant extract widely used in clinical practice. This review aimed to summarize and to grade the available evidence on the association between berberine consumption and health-related outcomes. The PubMed, Cochrane Library, and Embase databases were searched for meta-analyses of randomized controlled trials (RCTs) assessing the efficacy and safety of berberine from inception to June 30, 2022. The AMSTAR-2 and GRADE system were used to assess the methodological quality and evidence level of the included meta-analyses. A total of 11 eligible meta-analyses were identified from 235 publications, which were published in peer-reviewed journals between 2013 and 2022. The results revealed that berberine significantly affects blood glucose levels, insulin resistance, blood lipids, body parameters and composition, inflammatory markers, colorectal adenomas, and Helicobacter pylori infections as compared to controls. Common side effects of berberine consumption include gastrointestinal symptoms, such as constipation and diarrhea. Berberine is a safe medicinal plant ingredient that improves various clinical outcomes; however, there is a need for improvement of methodological quality in published meta-analyses. Additionally, the clinical effects of berberine need to be confirmed in high-quality RCTs.

Efficacy and safety of berberine for several cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Berberine has been widely used for the adjuvant therapy of several cardiovascular diseases (CVDs). However, evidence for its efficacy remains controversial. PURPOSE: This study aimed to evaluate the efficacy and safety of berberine in CVDs. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We searched ten electronic databases for articles from inception to December 23, 2022. RCTs comparing berberine alone or combined with statins versus statins or routine for CVDs were included. Meta-analysis was performed according to the Cochrane Handbook. RESULTS: Forty-four RCTs were included with 4606 patients. There were no differences between berberine alone and routine or statins in improving total cholesterol (TC) (SMD, 0.43; 95% CI, -0.39 to 1.24; p = 0.30; I2 = 95%), triglyceride (TG) (SMD, -0.14; 95% CI, -0.49 to 0.21; p = 0.44; I2 = 76%), low-density lipoprotein cholesterol (LDL-C) (SMD, 0.69; 95% CI, -0.23 to 1.60; p = 0.14; I2 = 96%), high-density lipoprotein cholesterol (HDL-C) (SMD, 0.55; 95% CI, -0.48 to 1.57; p = 0.30; I2 = 96%), and Crouse score levels. Berberine alone significantly reduced National Institute of Health Stroke Scale (NIHSS) score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intima-media thickness (IMT) levels than routine therapy. Berberine plus statins significantly reduced TC, TG, LDL-C, NIHSS score, hs-CRP, TNF-α, IMT, Crouse score, and number of unstable plaques levels than routine or statins. However, no differences were found between groups in improving HDL-C and IL-6 levels. There were no significant differences between groups in the incidence of adverse reactions. CONCLUSION: This study suggests that berberine may be a promising alternative for CVDs with no serious adverse reactions. However, our results may be limited by the quality of existing research. High-quality RCTs are needed to provide more convinced evidence.

Efficacy and safety of triple therapy containing berberine hydrochloride, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori.

OBJECTIVE: To estimate the effectiveness and safety of triple therapy containing berberine, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori (H. pylori). METHODS: This prospective, randomized controlled, open-label, noninferiority trial included treatment-naive patients with H. pylori infection who were randomly allocated at a ratio of 1:1 into the berberine triple therapy group (berberine hydrochloride 300 mg thrice daily, amoxicillin 1 g twice daily, and rabeprazole 10 mg twice daily) or standard bismuth-containing quadruple therapy group (amoxicillin 1 g twice daily, rabeprazole 10 mg twice daily, clarithromycin 500 mg twice daily, and bismuth tartrate 200 mg twice daily) for 14 days. Negative 13 C/14 C-urea breath test at 4 weeks after completion of the therapy was regarded as successful eradication. RESULTS: Altogether 262 and 262 patients received berberine triple therapy and bismuth-containing quadruple therapy, respectively. Both intention-to-treat (79.8% vs 80.9%, P = 0.742) and per-protocol analyses (83.6% and 85.1%, P = 0.636) showed comparable eradication rate between the two groups, indicating a noninferior eradication rate (the lower limit of the 95% confidence interval over -10% [-7.9% and -7.87%, respectively]). Adverse events more commonly occurred in the bismuth-containing quadruple-therapy group (8.8% vs 16.0%, P = 0.012), while patient compliance and symptom improvement of the two regimens were comparable. CONCLUSION: Triple therapy containing berberine, amoxicillin and rabeprazole is noninferior to bismuth-containing quadruple therapy in the initial treatment for H. pylori eradication.

Effects of treatment with monacolin K, berberine and coenzyme Q10 on lipid metabolism in patients with moderate cardiovascular risk.

OBJECTIVE: The use of nutritional supplements to treat hypercholesterolemia is gradually increasing, however further studies on their efficacy and safety are required. PATIENTS AND METHODS: The present clinical trial included patients with moderate hypercholesterolemia and cardiovascular risk who were treated either with a nutraceutical preparation containing 3.75mg of monacolin K, 515mg of berberine and 50mg of coenzyme Q10 per tablet (Lipok®) or with a placebo. The clinical and laboratory variables were analyzed at baseline and at three and six months. None of the patients was diabetic, and none was being treated with lipid-lowering drugs or with any other nutritional supplements affecting lipid metabolism. RESULTS: In patients of the intervention group and of the placebo group, baseline LDL-C was 134.7mg/dL (14.4) and 138.7mg/dL (15.2), respectively. At three months after treatment start, LDL-C had decreased by 26.1mg/dL (-32.4 to 19.7) and increased by 4.5mg/dL (-1.5 to 10.5) in the respective groups. In the intervention group, a similar decrease in non-HDL-C and total cholesterol was observed, while no significant changes were observed in either group for HDL-C, triglycerides and lipoprotein(a). A good tolerance and safety profile was observed. CONCLUSION: In conclusion, this study demonstrates that the combination of monacolin K, berberine and coenzyme Q10 is effective and safe for treating hypercholesterolemia in patients with a moderate degree of excess LDL-C and cardiovascular risk.

Berberine ameliorates DSS-induced intestinal mucosal barrier dysfunction through microbiota-dependence and Wnt/ß-catenin pathway.

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/ß-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/ß-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.

Efficacy and safety of berberine in preventing recurrence of colorectal adenomas: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine(BBR) is a kind of isoquinoline alkaloids extracted from the rhizomes of Coptis chinensis Franch., which was the main active ingredient. Accumulating evidence has shown that it has potential pharmacological effects in preventing the recurrence of colorectal adenomas. AIM OF THE STUDY: The roles of BBR in the overall recurrence of colorectal adenoma have still not been assessed because of the limitations of the available data and the restriction of a single study. Therefore, we evaluated the effectiveness and safety of BBR in preventing the recurrence of colorectal adenomas through a systematic review and meta-analysis of available data. MATERIALS AND METHODS: We searched four English databases (PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials (CENTRAL), Embase and Web of Science) and four Chinese language databases (Chinese Biomedicine (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP) and the WanFang Database) from their inception through October 2020. Meta-analysis was performed with RevMan5.3 software after data extraction and the quality of studies assessment. RESULTS: Three randomized controlled clinical trials were included with 1076 patients. Our results illustrated that 1-year and 2-year supplementation with BBR was associated with lower recurrence rate of colorectal adenoma (RR 0.69, 95% CI 0.57 to 0.84, p=0.0001; RR 0.75, 95% CI 0.64 to 0.88, p=0.0004). The relative risk of oral BBR for 1 year and 2 years is not comparable, for 2-year efficacy outcomes were assessed in all participants who had at least one colonoscopy with pathological evaluation after baseline (lots of participants completed the first colonoscopy but discontinued during the second follow-up interval.). Moreover, the results also suggest that BBR had more adverse events than placebo (RR 2.91, 95% CI 1.24 to 6.85, p=0.01). Through the full-text reading, no serious adverse events were observed, and constipation was the most common event which disappears once the drug is discontinued. CONCLUSION: Generally, the present study indicated that BBR has a comparable therapeutic effect on the prevention of colorectal adenomas recurrence. Adverse reactions are worthy of attention which requires additional studies to obtain a precise conclusion. PROSPERO REGISTRATION NO: CRD42020209135.

Adjunctive berberine reduces antipsychotic-associated weight gain and metabolic syndrome in patients with schizophrenia: a randomized controlled trial.

AIM: The aim of this study was to evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic-associated weight gain and metabolic syndrome. METHODS: One hundred thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome were recruited. They were randomly assigned to berberine (600 mg/d, n = 58) or placebo (n = 55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight. Secondary outcomes included body mass index, waist circumference, serum glucose and lipid profiles, and the severity of psychotic symptoms. RESULTS: Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD], -0.75; 95% CI, -1.42 to -0.07 [P = 0.031, d = 0.41]) and 12 weeks (MD, -1.08; 95% CI, -1.76 to -0.40 [P = 0.002, d = 0.59]). Patients who received berberine also showed statistically significant improvements in end point in body mass index (MD, -0.41; 95% CI, -0.65 to -0.17 [P = 0.001, d = 0.64]), total cholesterol (MD, -0.58; 95% CI, -0.74 to -0.41 [P < 0.001, d = 1.31]), low-density lipoprotein (MD, -0.52; 95% CI, -0.68 to -0.35 [P < 0.001, d = 1.19]), and glycated hemoglobin (MD, -0.09; 95% CI, -0.18 to 0 [P = 0.05, d = 0.37]). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo. CONCLUSION: The findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and metabolic syndrome.

A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes.

Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease -4.8% vs. -2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes.

Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial.

Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist-hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (-0.39 mmol/L, 95% confidence interval (CI) -0.70 to -0.08) and high-density lipoprotein cholesterol (-0.07 mmol/L, 95% CI -0.13 to -0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist-hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.

Efficacy and safety of berberine for dyslipidemia: study protocol for a randomized double-blind placebo-controlled trial.

BACKGROUND: Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease and a leading cause of death worldwide. The clinical utility of commonly used lipid-lowering drugs such as statins and fibrates is sometimes limited by the occurrence of various adverse reactions. Recently, berberine (BBR) has received increasing attention as a safer and more cost-effective option to manage dyslipidemia. Thus, a high-quality randomized controlled trial to evaluate the efficacy and safety of BBR in the treatment of dyslipidemia is deemed necessary. METHODS/DESIGN: This is a randomized, double-blind, and placebo-controlled clinical trial. A total of 118 patients with dyslipidemia will be enrolled in this study and randomized into two groups at a ratio of 1:1. BBR or placebo will be taken orally for 12 weeks. The primary outcome is the percentage of low-density lipoprotein cholesterol reduction at week 12. Other outcome measures include changes in other lipid profiles, high sensitivity C-reactive protein, blood pressure, body weight, Bristol Stool Chart, traditional Chinese medicine symptom form, adipokine profiles, and metagenomics of intestinal microbiota. Safety assessment includes general physical examination, blood and urine routine test, liver and kidney function test, and adverse events. DISCUSSION: This trial may provide high-quality evidence on the efficacy and safety of BBR for dyslipidemia. Importantly, the findings of this trial will help to identify patient and disease characteristics that may predict favorable outcomes of treatment with BBR and optimize its indication for clinical use. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900021361 . Registered on 17 February 2019.

Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence.

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.

Goldenseal (Hydrastis canadensis L.) and its active constituents: A critical review of their efficacy and toxicological issues.

Goldenseal (Hydrastis canadensis L.) is a medicinal plant widely used in various traditional systems of medicine and as a food supplement. It has been traditionally used by Native Americans as a coloring agent and as medicinal remedy for common diseases and conditions like wounds, digestive disorders, ulcers, skin and eye ailments, and cancer. Over the years, goldenseal has become a popular food supplement in the USA and other regions. The rhizome of this plant has been used for the treatment of a variety of diseases including, gastrointestinal disorders, ulcers, muscular debility, nervous prostration, constipation, skin and eye infections, cancer, among others. Berberine is one of the most bioactive alkaloid that has been identified in different parts of goldenseal. The goldenseal extract containing berberine showed numerous therapeutic effects such as antimicrobial, anti-inflammatory, hypolipidemic, hypoglycemic, antioxidant, neuroprotective (anti-Alzheimer's disease), cardioprotective, and gastrointestinal protective. Various research finding suggest the health promoting effects of goldenseal components and their extracts. However, few studies have also suggested the possible neurotoxic, hepatotoxic and phototoxic activities of goldenseal extract and its alkaloids. Thus, large randomized, double-blind clinical studies need to be conducted on goldenseal supplements and their main alkaloids to provide more evidence on the mechanisms responsible for the pharmaceutical activity, clinical efficacy and safety of these products. Thus, it is very important to review the scientific information about goldenseal to understand about the current scenario.

[Systematic review and Meta-analysis on efficacy and safety of berberine for dyslipidemia].

To evaluate the clinical efficacy and safety of berberine in the treatment of dyslipidemia. In this review, CNKI, WanFang, VIP, CBM, PubMed, Cochrane Library, EMbase, and Medline(OVID) were retrieved from database establishment to January, 2019 in any language. Randomized controlled trials(RCTs) of berberine with or without lipid-lowering drugs vs placebo, without drugs or lipid-lowering drugs only in treatment of dyslipidemia were collected. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. Then RevMan 5.3 software was used for Meta-analysis. A total of 25 trials were included, covering 3 042 cases, including 1 552 cases in the experimental group and 1 490 cases in the control group. The clinical heterogeneity of the included trials was relatively high, and the methodological quality of most trials was generally low, with bias in terms of random sequence generation, allocation hiding, blind method and result data. Interventions were divided into different subgroups for analysis. Meta-analysis suggested that use berberine alone or along with lipid lowing drugs could reduce TC, TG, LDL-C levels and increased HDL-C levels with statistically significant difference as compared with control group. As compared with control group, there was no statistically significant difference in the incidence of adverse events. No severe adverse effects were reported in all trials. Berberine has good efficacy and safety in the treatment of dyslipidemia. Due to the quality limitations of the included trials, the above conclusions need to be further verified by high-quality, large sample size and multi-center clinical trials.

Berberine attenuated olanzapine-induced metabolic alterations in mice: Targeting transient receptor potential vanilloid type 1 and 3 channels.

Transient receptor potential vanilloid type 1 (TRPV1) channels are emerging therapeutic targets for metabolic disorders. Berberine, which is a modulator of TRPV1, has proven antiobesity and antidiabetic potentials. The present study was aimed to investigate the protective effects of berberine in olanzapine-induced alterations in hypothalamic appetite control, inflammation and metabolic aberrations in mice targeting TRPV1 channels. Female BALB/c mice (18-23 g) were treated with olanzapine (6 mg/kg, p.o.) for six weeks to induce metabolic alterations, while berberine (100 and 200 mg/kg, p.o.) and metformin (100 mg/kg, p.o) were used as test and standard interventions respectively. Weekly assessment of feed-water intake, body temperature and body weight was done, while locomotion was measured at the end of week 1 and 6. Serum glucose and lipid profile were assessed by biochemical methods, while other serum biomarkers were assessed by ELISA. qPCR was used to quantify the mRNA expression in the hypothalamus. Olanzapine treatment significantly increased the feed intake, weight gain, adiposity index, while reduced body temperature and locomotor activity which were reversed by berberine treatment. Berberine treatment reduced serum ghrelin and leptin levels as well decrease in hypothalamic mRNA expression of orexigenic neuropeptides, inflammatory markers and ghrelin receptor in olanzapine-treated mice. Olanzapine treatment increased expression of TRPV1/TRPV3 in the hypothalamus which was significantly decreased by berberine treatment. Our results suggest that berberine, by TRPV1/TRPV3 modulation, attenuated the olanzapine-induced metabolic alterations in mice. Hence berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics.