Danshensu and Notoginsenoside R1 Combination Alleviates Obesity in Mice Via Modification of Gut Microbiota and Short-Chain Fatty Acids

Objectives The current study evaluated the protective mechanism of Danshensu and Notoginsenoside R1 combination (DR1) on obesity from the perspective of gut microbiota and short-chain fatty acids (SCFAs). Methods Male C57BL/6J mice were fed either a normal diet or a high-fat diet (HFD). DR1 (60 mg/kg) was administered to both normal and HFD-induced obese mice for 12 weeks. The obese phenotype and pharmacodynamics effects were assessed through hematoxylin-eosin staining of epididymal fat, liver, small intestine, and colon tissues, as well as serum biochemical detection. Moreover, 16S ribosomal ribonucleic acid (16S rRNA) sequencing was employed to profile the taxonomy and function of gut microbiota, while SCFAs were quantified using ultra-performance liquid chromatography coupled with mass spectrometry methods. Results Compared to HFD group, the tissue lesions were significantly alleviated by DR1 treatment in obese mice, accompanied by the significant reduction of average body, epididymal fat and liver weights, as well as the normalization of insulin sensitivity and glucose homeostasis ( P < .05, P < .01 or P < .001). 16S rRNA sequencing analysis showed that DR1 treatment potently ameliorated HFD-induced dysbiosis of gut microbial composition and function. Notably, DR1 reversed the ratio of Firmicutes/ Bacteroidetes to normality. Moreover, DR1 improved intestinal barrier structures and enhanced SCFAs concentrations in the caecal contents (especially propionate and butyrate). Conclusion These results suggested that DR1 could reverse the gut microbial dysbiosis and increased SCFAs levels in HFD-induced obese mice, thereby ultimately supporting the anti-obesity value of DR1.