Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center, Shaanxi University of Chinese Medicine, 712083, Xianyang, Shaanxi, PR China.
Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center, Shaanxi University of Chinese Medicine, 712083, Xianyang, Shaanxi, PR China.
Biomed Pharmacother. 2021 Mar;135:111131. doi: 10.1016/j.biopha.2020.111131. Epub 2020 Dec 28.
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.
贯叶金丝桃（HP）是一种众所周知的天然药物，对绝经后高胆固醇血症有潜在作用。然而，在雌激素缺乏的情况下，HP 提取物对肠道微生物群及其相关代谢物的影响尚未报道，而肠道微生物群及其相关代谢物在代谢性疾病的发生中起着至关重要的作用。本研究旨在探讨 HP 提取物对去卵巢（OVX）大鼠肠道微生物组成及相关代谢物谱的影响，并揭示病理指标与肠道微生物组成及代谢物变化之间的关系。测定体重、血清参数、肝脂和组织形态学。采用 16S rRNA 测序分析微生物组成。定量测定粪便短链脂肪酸（SCFAs）和血清胆汁酸。采用 Spearman 秩相关检验研究病理指标与肠道微生物群和代谢物变化的相关性。采用 PCR 测定肝脏中 3-羟-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶、胆固醇 7α-羟化酶（CYP7A1）和胆固醇 27-羟化酶（CYP27A1）以及盲肠中 G 蛋白偶联受体（GPCR；GPR43 和 GPR41）、ZO-1 和 occludin 的基因表达。与假手术组大鼠相比，OVX 大鼠的微生物组成和代谢物谱明显改变。鉴定出 12 个细菌属、5 种 SCFAs 和 12 种胆汁酸为差异生物标志物。差异属、SCFAs 和胆汁酸与体重、总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）密切相关。在 OVX 大鼠中，HP 给药可显著逆转体重增加、血清脂质紊乱和肝脂肪变性等病理症状，同时重建肠道微生物组成和代谢物谱。此外，HP 给药可显著上调 CYP7A1、GPR43 和 GPR41 的水平。综上所述，HP 可改善雌激素缺乏引起的高胆固醇血症。其潜在机制可能与改善肠道微生物群组成和相关代谢物谱以及增加胆汁酸分泌有关。
