Xiehuang San Extract Attenuates Insulin Resistance in Obese Rats via Gut Microbiota Modulation: Experimental Evidence

BACKGROUND Obesity-induced insulin resistance significantly contributes to the global increase in type 2 diabetes, with gut microbiota alterations playing a critical role. Traditional herbal formulations, such as Xiehuang San (XHS), have been used for centuries in Chinese medicine. However, their mechanisms - particularly via the gut-liver-metabolism axis - remain to be fully elucidated. This study aimed to evaluate the efficacy of XHS in improving insulin resistance through metabolic and microbial modulation. MATERIAL AND METHODS A high-fat diet-induced obese insulin-resistant rat model (n=30) was established using male rats. Rats were randomized into 6 groups and treated with low, medium, or high doses of XHS, metformin, or vehicle control via daily gavage for 8 weeks. Metabolic parameters, including fasting blood glucose (FBG), fasting insulin (FINS), the homeostatic model assessment for insulin resistance (HOMA-IR), oral glucose tolerance (OGTT), and insulin tolerance tests (ITT) were assessed. Liver histology and lipid profiles were analyzed, and 16S rRNA sequencing was used to examine gut microbiota composition. RESULTS XHS treatment significantly reduced FBG (~25%), FINS (~30%), and HOMA-IR scores compared with the model group (P<0.05), with effects comparable to metformin. OGTT and ITT improvements were dose-dependent. XHS also ameliorated hepatic steatosis and improved lipid profiles (eg, lowered triglycerides and low-density lipoprotein cholesterol, and elevated high-density lipoprotein cholesterol). Gut microbiota analysis revealed that XHS decreased the Firmicutes/Bacteroidetes ratio and selectively increased Bacteroides while reducing Escherichia-Shigella, suggesting a reshaping of microbial diversity and abundance. CONCLUSIONS These findings suggest that XHS may enhance insulin sensitivity and improve metabolic outcomes in obese rats, partly via gut microbiota modulation. Further studies are needed to isolate its active components, clarify molecular pathways, and evaluate translational relevance in human subjects.