Department of Pharmacy, Hunan Provincial People's Hospital (The First Affiliate Hospital of Hunan Normal University), Changsha, Hunan, 410000, P. R. China.
Hunan Provincial Key Laboratory of Emergency and Critical Care Metabolomics, Changsha, Hunan, 410000, P. R. China.
Food Funct. 2023 Feb 21;14(4):2112-2127. doi: 10.1039/d2fo03509j.
Hyperlipidemia (HLP) is one of the main factors leading to cardiovascular diseases. Quercetin (QUE) is a naturally occurring polyhydroxy flavonoid compound that has a wide range of pharmacological effects. However, the potential mechanism for treating HLP remains unclear. Thus, the study aimed to investigate the role of QUE in HLP development and its underlying mechanisms in HLP rats based on the analysis of gut microbiota and plasma metabolomics. Following the establishment of an HLP model in rats, QUE was orally administered. Plasma samples and fecal samples were collected from HLP rats for microbiome 16S rDNA sequencing and metabolic UPLC-Q-Exactive-MS analysis. The results suggested that QUE could regulate dyslipidemia and inhibit the levels of TC, TG, and LDL-c. Additionally, histopathological findings revealed that QUE could reduce lipid deposition, ameliorate hepatic injury and steatosis in HFD-induced rats, and have a protective effect on the liver. The analysis and identification of plasma metabolomics showed that the intervention effect of QUE on HLP rats was related to 60 differential metabolites and signal pathways such as lactosamine, 11b-hydroxyprogesterone, arachidonic acid, glycerophospholipid, sphingolipid, glycerolipid, and linoleic acid metabolism. Combined with fecal microbiological analysis, it was found that QUE could significantly change the composition of intestinal flora in HLP rats, increase beneficial bacteria, and reduce the composition of harmful bacteria, attenuating the / ratio. The results of correlation analysis showed that the relative abundance level of , , , , and was closely related to the change of differential metabolites. In summary, combined with metabolomics and gut microbiota studies, it is found that QUE can reduce lipid levels and improve liver function. The potential mechanism may be the regulation of metabolism and intestinal flora that play a role in reducing lipid levels, to achieve the purpose of treatment of HLP.
高脂血症（HLP）是导致心血管疾病的主要因素之一。槲皮素（QUE）是一种天然存在的多羟基类黄酮化合物，具有广泛的药理作用。然而，其治疗 HLP 的潜在机制尚不清楚。因此，本研究旨在基于肠道微生物组和血浆代谢组学分析，探讨 QUE 在 HLP 大鼠发展中的作用及其潜在机制。在成功建立 HLP 大鼠模型后，对其进行 QUE 灌胃处理。收集 HLP 大鼠的血浆样本和粪便样本，进行微生物组 16S rDNA 测序和代谢物 UPLC-Q-Exactive-MS 分析。结果表明，QUE 可调节血脂异常并抑制 TC、TG 和 LDL-c 的水平。此外，组织病理学发现 QUE 可减少脂质沉积，改善 HFD 诱导的大鼠肝损伤和脂肪变性，对肝脏具有保护作用。血浆代谢组学的分析和鉴定表明，QUE 对 HLP 大鼠的干预作用与 60 种差异代谢物及乳糖胺、11b-羟基孕酮、花生四烯酸、甘油磷脂、鞘脂、甘油酯和亚油酸代谢等信号通路有关。结合粪便微生物学分析，发现 QUE 可显著改变 HLP 大鼠肠道菌群的组成，增加有益菌，减少有害菌的组成，降低 / 比值。相关性分析结果表明， 、 、 、 、 的相对丰度水平与差异代谢物的变化密切相关。综上所述，结合代谢组学和肠道微生物组学研究发现，QUE 可降低血脂水平，改善肝功能。其潜在机制可能是通过调节代谢和肠道菌群来发挥降低血脂水平的作用，从而达到治疗 HLP 的目的。
