Guizhi Fuling Wan, Chinese Herbal Medicine, Ameliorates Insulin Sensitivity in PCOS Model Rats With Insulin Resistance via Remodeling Intestinal Homeostasis

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disease with reproductive dysfunction and metabolic disorder in women of childbearing age. Gastrointestinal microbiome contributes to PCOS through mediating insulin resistance. Guizhi Fuling Wan, Chinese herbal medicine, can treat PCOS with insulin resistance (PCOS-IR), but the underlying mechanism is not clear. The aim of this study was to characterize the exact mechanism of Guizhi Fuling Wan action and whether it is related to the regulation of intestinal flora structure. We induced PCOS-IR rat model by means of letrozole sodium carboxymethyl cellulose (CMC-na) solution combined with high-fat emulsion administration and randomly divided it into blank control group (K), model control group (M), low dose of Guizhi Fuling Wan group (D), middle dose of Guizhi Fuling Wan group (Z), high dose of Guizhi Fuling Wan group (G) and positive drug (Metformin) control group (Y). After 36 days of modeling and treatment, serum and stool samples from all rats were collected for a follow-up analysis. The data display that, compared with K group, elevated testosterone and HOMA-IR, turbulent estrous cycles and polycystic ovaries in M group, indicating the PCOS-IR rat model is successfully established. Increased fasting insulin is associated with higher inflammation(plasma TNF-α, IL-6, and HS-CPR concentration were determined) in M group, and the altered intestinal flora (compared with the K group, in M group the relative abundance of Alloprevotella was decreased significantly, while the relative abundance of Lachnospiraceae UCG-008, Lachnospiraceae NK4A136, Lactobacillus, Ruminiclostridium 9, and Ruminococcaceae UCG-003 was increased significantly) induced the secretion of inflammatory markers. On the other hand, Guizhi Fuling Wan can alleviate inflammation, improve insulin resistence: Lower inflammation decreased fasting insulin can be seen in G group compared with M group, this effect is related to the regulating effect of Guizhi Fuling Wan on intestinal flora (in G group, the relative abundance of Alloprevotella, Ruminococcaceae UCG-003, and Lachnospiraceae UCG-008 was increased significantly, compared with M group). This research demonstrates Guizhi Fuling Wan improve insulin resistance in polycystic ovary syndrome with the underlying mechanism of regulating intestinal flora to control inflammation. It would be useful to promote the therapeutic effect of Guizhi Fuling Wan on PCOS-IR.

Keywords: Guizhi Fuling Wan; gastrointestinal microbiome; homeostasis; insulin resistance; polycystic ovary syndrome.