Improvements in estrogen deficiency-induced hypercholesterolemia by Hypericum perforatum L. extract are associated with gut microbiota and related metabolites in ovariectomized (OVX) rats

Biomedicine & Pharmacotherapy

Zhongxing Song¹  Min Li¹  Yanru Liu²  Dahai Jiang²  Peifeng Wei²  Xinbo Shi²  Ningjuan Yang²  Xiaohong Li³  Yafeng Yan³  Lin Chen³  Fan Cao³  Zhishu Tang³ 

[1]Corresponding authors.

[2]Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center, Shaanxi University of Chinese Medicine, 712083, Xianyang, Shaanxi, PR China

[3]

[4]Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, State Key Laboratory of Research &

关键词: Gut microbiota;    Short-chain fatty acids;    Bile acids;    Hypericum perforatum L.;    Estrogen deficiency;    Hypercholesterolemia;   

DOI  :  

来源: DOAJ

【 摘 要 】

Hypericum perforatum L. (HP), a well-known natural medicine, has a potential effect on menopausal hypercholesterolemia. However, the effect of HP extract on gut microbiota and related metabolites, which play vital roles in metabolic disease occurrence, in the context of estrogen deficiency have not yet been reported. The aims of the present study were to investigate the effects of HP extract on gut microbial composition and related metabolite profiles in ovariectomized (OVX) rats and reveal the relationships between pathological indicators and alterations in both gut microbial composition at the genus level and metabolites. Body weight, serum parameters, liver lipids and histomorphology were determined. Microbial composition was analyzed using 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) and serum bile acids were quantitatively measured. Correlations between pathological indicators and alteration in gut microbiota and metabolites were investigated using Spearman's rank correlation test. Gene expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7α-hydroxylase (CYP7A1) and cholesterol 27-hydroxylase (CYP27A1) in the liver and G protein-coupled receptors (GPCRs; GPR43 and GPR41), ZO-1 and occludin in the cecum were determined by PCR. Microbial composition and metabolite profiles were significantly changed in OVX rats compared with sham rats. Twelve bacterial genera, 5 SCFAs and 12 bile acids were identified as differential biomarkers. Differential genera, SCFAs and bile acids were closely associated with weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In OVX rats, HP administration can significantly reverse the pathological symptoms of body weight gain, serum lipid disorders and hepatic steatosis, at the meanwhile, reestablish gut microbial composition and metabolite profiles. Moreover, HP administration significantly upregulated the levels of CYP7A1, GPR43 and GPR41. In conclusion, HP can ameliorate estrogen deficiency-induced hypercholesterolemia. The underlying mechanism may be associated with improvements in gut microbiota composition and the profile of related metabolites as well as increases in bile acid secretion.

【 授权许可】

Unknown