Berberine — a plant-based rival to metformin?

Aim of the study: Berberine has been shown to regulate glucose and lipid metabolism in vitro and in vivo. This pilot study was designed to determine the efficacy and safety of berberine in the treatment of patients with type 2 diabetes mellitus.

Results: Total cholesterol and low-density lipoprotein cholesterol also decreased significantly. During the trial, 20 (34.5%) patients experienced temporary gastrointestinal side effects. No functional liver or kidney damage was observed in any patient. In conclusion, this pilot study indicates that berberine is a potent oral blood-glucose-lowering agent with beneficial effects on lipid metabolism.

Aim of the study: Coptis chinensis (Huanglian), a key component in numerous classical Chinese herbal formulas, is traditionally applied for treating metabolic diseases based on its activity including clear heat, dry dampness, purge fire, and detoxify.

Results: This article systematically reviews the modern separation, extraction, and purification techniques for BBR, its molecular pharmacological mechanisms, and advances in novel delivery technologies for diabetes treatment. This review synthesizes evidence that BBR exerts its anti-diabetic effects through multi-tiered mechanisms converging on the amelioration of insulin resistance and systemic inflammation. The findings provide a theoretical foundation for optimizing BBR's clinical application and promote the transformation of traditional Chinese medicine from empirical usage to a scientific and standardized therapeutic paradigm. By integrating BBR's multi-target pharmacology with cutting-edge delivery technologies, this review provides a transformative perspective, positioning BBR not merely as a natural product but as a scaffold for the rational development of next-generation, multi-target diabetes therapeutics.

Aim of the study: Berberine and metformin, both established pharmaceutical agents with herbal origins, have incidental beneficial effects on multiple diseases, including diabetes. These effects have been speculated to occur via the gut microbiome.

Results: Both treatments effectively restored intestinal SCFA content, reduced serum LPS levels, relieved intestinal inflammation, and repaired the intestinal barrier structure. Treatment with metformin or berberine modified the gut microbiome in db/db mice, increasing the number of SCFA-producing bacteria (e.g., Butyricimonas, Coprococcus, Ruminococcus) and reducing opportunistic pathogens (e.g., Prevotella, Proteus). An increased abundance of other probiotics, including Lactobacillus and Akkermansia, was also observed. Berberine and metformin can modify the composition of the gut microbiome and reduce body weight, blood glucose levels, and intestinal inflammation in db/db mice, demonstrating their effectiveness in reducing diabetic complications in this model.

Aim of the study: Metformin is a versatile biguanide drug primarily prescribed for type II diabetes. Despite its extensive use, the mechanisms underlying its clinical effects, including attenuated postprandial glucose excursions and elevated intestinal glucose uptake, remain unclear.

Results: Using human metabolomic data and an orthogonal genetics approach in male mice, we demonstrate that metformin suppresses citrulline synthesis, a metabolite generated exclusively by small intestine mitochondria, and increases GDF15 by inhibiting the mitochondrial respiratory chain at complex I. This inhibition co-opts the intestines to function as a glucose sink, driving the uptake of excess glucose and its conversion to lactate and lactoyl-phenylalanine. We also find that glucose lowering by metformin is due to repeated bolus exposure rather than a cumulative chronic response. Notably, the efficacy of phenformin, another biguanide, and berberine, a structurally unrelated nutraceutical, similarly depends on intestine-specific mitochondrial complex I inhibition, underscoring a shared therapeutic mechanism.

Aim of the study: Metformin is a therapeutically versatile biguanide drug primarily prescribed for type II diabetes. Despite its extensive use, the mechanisms underlying many of its clinical effects, including attenuated postprandial glucose excursions, elevated intestinal glucose uptake, and increased production of lactate, Lac-Phe and GDF15, remain unclear.

Results: Here, we map these and other clinical effects of metformin to intestine-specific mitochondrial complex I inhibition. Using human metabolomic data and an orthogonal genetics approach in male mice, we demonstrate that metformin suppresses citrulline synthesis, a metabolite generated exclusively by small intestine mitochondria, and increases GDF15 by inhibiting the mitochondrial respiratory chain at complex I. This inhibition co-opts the intestines to function as a glucose sink, driving uptake of excess glucose and converting it to lactate and Lac-Phe. Notably, the glucose-lowering effect of another biguanide, phenformin, and berberine, a structurally unrelated nutraceutical, similarly depends on intestine-specific mitochondrial complex I inhibition, underscoring a shared therapeutic mechanism.

Aim of the study: Antipsychotic-induced metabolic syndrome complicates the clinical management of schizophrenia. This investigation seeks to examine berberine's efficacy and safety as adjunctive therapy in schizophrenia patients with metabolic syndrome.

Results: Three eligible RCTs (n = 233) were incorporated. Adjunctive berberine demonstrated superior efficacy over controls in reducing body weight (standardized mean difference (SMD) = -0.56, I² = 0%; P = 0.0003), body mass index (SMD = -0.51, I² = 0%; P = 0.0001), waist circumference (SMD = -0.31, I² = 20%; P = 0.04), total cholesterol (mean difference (MD) = -0.43, I² = 63%; P = 0.004), triglycerides (MD = -0.31, I² = 0%; P < 0.0001), and fasting plasma glucose (MD = -0.30, I² = 0%; P = 0.005). No significant differences existed in low density lipoprotein cholesterol (MD = -0.27, I² = 75%; P = 0.1), high density lipoprotein cholesterol (MD = -0.02, I² = 31%; P = 0.56), glycated hemoglobin (MD = -0.22, I² = 67%; P = 0.21), systolic blood pressure (MD = -1.62, I² = 0%; P = 0.17), or diastolic blood pressure (MD = -1.68, I² = 39%; P = 0.15).