Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet.

BACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS. METHODS: PCOS rat models were established using letrozole combined with a high-fat diet. Ten rats were randomly selected as a PCOS control group (PCOS). The other three groups (n = 10/group) were additionally supplemented with different doses of orlistat (low, medium, high). Then, fecal samples of the PCOS and ORL-PCOS groups were analysed by 16S rRNA gene sequencing and untargeted metabolomics. Blood samples were collected to detect serum sex hormones and lipids. RESULTS: The results showed that orlistat attenuated the body weight gain, decreased the levels of T, LH, the LH/FSH ratio, TC, TG and LDL-C; increased the level of E2; and improved estrous cycle disorder in PCOS rats. The bacterial richness and diversity of the gut microbiota in the ORL-PCOS group were higher than those in the PCOS group. The ratio of Firmicutes to Bacteroidetes was decreased with orlistat treatment. Moreover, orlistat treatment led to a significant decrease in the relative abundance of Ruminococcaceae and Lactobacillaceae, and increases in the abundances of Muribaculaceae and Bacteroidaceae. Metabolic analysis identified 216 differential fecal metabolites in total and 6 enriched KEGG pathways between the two groups, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction and vitamin digestion and absorption. Steroid hormone biosynthesis was the pathway with the most significant enrichment. The correlations between the gut microbiota and differential metabolites were calculated, which may provide a basis for understanding the composition and function of microbial communities. CONCLUSIONS: Our data suggested that orlistat exerts a PCOS treatment effect, which may be mediated by modifying the structure and composition of the gut microbiota, as well as the metabolite profiles of PCOS rats.

The protective effect of tanshinone IIa on endothelial cells: a generalist among clinical therapeutics.

INTRODUCTION: Tanshinone IIa (TSA) has been approved to treat cardiovascular diseases by the China State Food and Drug Administration. TSA has exhibited a variety of pharmacological effects, including vasodilator, antioxidant, anti-inflammatory, and anti-tumor properties. Endothelial cells play an important physiological role in vascular homeostasis and control inflammation, coagulation, and thrombosis. Accumulating studies have shown that TSA can improve endothelial function through various pathways. AREAS COVERED: The PubMed database was reviewed for relevant papers published up to 2020. This review summarizes the current clinical and pharmaceutical studies to provide a systemic overview of the pharmacological and therapeutic effects of TSA on endothelial cells. EXPERT OPINION: TSA is a representative monomeric compound extracted from Danshen and it exhibits significant pharmacological and therapeutic properties to improve endothelial cell function, including alleviating oxidative stress, attenuating inflammatory injury, modulating ion channels and so on. TSA represents a spectrum of agents that are extracted from plants and can restore the endothelial function to establish the beneficial and harmless molecular therapeutics. This also suggests the possible detection of endothelial cells for very early diagnosis of diseases. In future, precise therapeutic methods will be developed to repair endothelial cells injury and recover endothelial dysfunction.