Effects of salvianolic acid A on intestinal microbiota and lipid metabolism disorders in Zucker diabetic fatty rats

Salvianolic acid A (SalA) is the main water-soluble component isolated from Salvia miltiorrhiza. This study explored the influences of SalA on intestinal microbiota composition and lipid metabolism in Zucker diabetic fatty (ZDF) rats. The 6-week-old male ZDF rats were treated with distilled water (N = 10) and low dose (SalA 0.5 mg/kg/d, N = 10), medium dose (SalA 1 mg/kg/d, N = 10), and high dose (SalA 2 mg/kg/d, N = 10) of SalA, with the male Zucker lean normoglycemic rats of the same week age as controls (given distilled water, N = 10). The blood glucose, body weight, and food intake of rats were examined. After 7 and 8 weeks of continuous administration, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed, respectively. Serum fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) were determined. Liver tissues were stained using hematoxylin–eosin (HE) and oil red O staining. Fecal samples were analyzed by 16S rRNA gene sequencing. Small intestinal tissues were stained using HE and immunohistochemistry. The tight junction proteins (ZO-1/Occludin/Claudin-1) and serum levels of LPS/TNF-α/IL-6 were evaluated. SalA reduced insulin resistance, liver injury, serum FFA, liver TC and TG levels in ZDF rats, and improved lipid metabolism. After SalA treatment, intestinal microbiota richness and diversity of ZDF rats were promoted. SalA retained the homeostasis of intestinal core microbiota. SalA reduced intestinal epithelial barrier damage, LPS, and inflammatory cytokines in ZDF rats. Overall, SalA can sustain intestinal microbiota balance and improve the lipid metabolism of ZDF rats.