Mechanism of action of buckwheat quercetin in regulating lipid metabolism and intestinal flora via Toll-like receptor 4 or nuclear factor κB pathway in rats on a high-fat diet

Buckwheat quercetin (QUE) was used as a dietary supplement to investigate the mechanism of QUE on the regulation of lipid metabolism and intestinal flora in hyperlipidemic rats.Here, using a high-fat diet-induced hyperlipidemia model, the intervention was carried out by gavage of QUE at doses of 50, 100, and 200 mg/kg. Serum lipid levels, liver biochemical parameters, and histopathologic changes in the liver and intestinal microorganisms were measured in rats by enzyme-linked immunosorbent assay, hematoxylin-eosin, and high-throughput sequencing, respectively.Our results found that QUE, at a dose of 200 mg/kg, significantly reduced body weight, liver index, and lipid levels in rats (P < 0.05); improved hepatic oxidative stress; and repaired liver injury. In addition, the upregulation of beneficial bacteria, such as christensenellaceae and Bifidobacterium, in the organism increased the content of short-chain fatty acids, thus interfering with intestinal pH and improving the intestinal environment, while downregulating the relative abundance of Proteobacteria and Eubacterium_coprostanoligenes_group, and regulating the overproduction of butyrate. The real-time fluorescence quantitative polymerase chain reaction results found that QUE inhibited the expression of Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA content and blocked the activation of the TLR4/NF-κB signaling pathway, thus affecting the downregulation of lipid levels and restoring intestinal homeostasis.A QUE dose of 200 mg/kg may improve lipid levels and the composition of intestinal flora through the TLR4/NF-κB pathway, suggesting that proteobacteria and christensenellaceae abundance changes may be biomarkers of potential diseases.