Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota are Attributable to Its Key Ingredient Berberine

Abstract

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.

Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway

“…Knocking down Aim2 and NLRP3 can alleviate renal fibrosis, inflammation, and injury (Kopalli et al, 2016;Cao et al, 2021). In clinical settings, GGQLD has frequently been adopted for the treatment of diabetes and UC (Xu et al, 2011;Zhao et al, 2020). GGQLD has been suggested to suppress the inflammatory signal transduction pathway and promote the antioxidant effect, thus improving UC.…”

“…Experiments in vitro and in vivo suggest that some active ingredients in GGQLD, like berberine, baicalin, and puerarin, obviously mitigate oxidative stress (OS) and inflammation (Dinesh and Rasool, 2017;Guarino et al, 2017;Yu et al, 2021). We previously discovered that GGQLD exerted diabetes-mitigating (Xu et al, 2011;Li et al, 2013;Zhang et al, 2013) and anti-inflammation effects through its active ingredients (Tian et al, 2013;Ryuk et al, 2017;Wu et al, 2019). Besides, inflammatory response, lipid, and glucose metabolic disorders are also important for HUA.…”

Effect of Gegen Qinlian Decoction on Hepatic Gluconeogenesis in ZDF Rats with Type 2 Diabetes Mellitus Based on the Farnesol X Receptor/Ceramide Signaling Pathway Regulating Mitochondrial Metabolism and Endoplasmic Reticulum Stress

“…Among them, puerarin, baicalin, baicalein, wogonin, berberine, and ammonium glycyrrhizinate could improve insulin resistance and also have good therapeutic effects on cardiovascular disease, diabetic nephropathy, diabetic retinopathy, and other complications caused by diabetes [ 8 – 17 ]. In animal experiments, studies have confirmed that GQD can play a role in the treatment of T2DM from regulating glucose and lipid metabolism, reducing oxidative stress response, changing the structure of intestinal flora, reducing the expression levels of inflammatory factors, and improving insulin resistance [ 7 , 18 , 19 ]. However, further elucidation of its possible molecular mechanism is still of great significance for the discovery and clinical application of monomer drugs of GQD.…”

Multi-Pharmacology of Berberine in Atherosclerosis and Metabolic Diseases: Potential Contribution of Gut Microbiota

“…Both treatments significantly changed the overall structure of the gut microbiota in a diabetic rat model and enriched butyrateproducing bacteria, such as Faecalibacterium and Roseburia, accompanied by significantly elevated SCFA levels in rat feces. This alleviated intestinal inflammation and lowered blood glucose (Xu et al, 2020). In addition, BBR and metformin have similar hypoglycemic effects.…”