Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100102, China.
Biomed Pharmacother. 2020 Nov;131:110719. doi: 10.1016/j.biopha.2020.110719. Epub 2020 Sep 17.
BACKGROUND: High-purine diet can cause gut microbiota disorder, which is closely related to the occurrence of hyperuricemia (HUA). At the same time, the development of HUA is often accompanied by renal impairment. Chicory, a natural medicine, has a significant effect on lowering uric acid. However, whether its concrete mechanism is associated with the regulation of gut microbiota and renal damage is still unclear. METHODS: Hyperuricemic quails induced by high-purine diet were used, and quails were divided into control (CON), model (MOD), and model plus high, middle, low doses of chicory. The uricosuric effect was evaluated by detecting the uric acid levels in serum and feces. Meanwhile, the morphology of intestine and kidney were observed by hematoxylin and eosin (HE) staining, and the expression of intestinal barrier junction proteins Occludin, Claudin-1 were detected by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Furthermore, the latent mechanism was clarified by analyzing 16S rRNA amplicon of gut microbiota and measuring the changes of LPS/TLR4 axis inflammatory response of the kidney by western blotting and enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that serum uric acid levels were significantly decreased, and the feces uric acid levels were noticeably increased after the intervention of chicory. In addition, chicory could repair the damage of intestinal mucosa and improve the permeability of intestinal barrier. Moreover, the 16S rRNA sequencing analysis uncovered that chicory restored gut microbiota by increasing the probiotics flora (Bifidobacterium, Erysipelotrichaceae) and reducing the pathogenic bacteria group (Helicobacteraceae). Furthermore, it was found that chicory reduced the LPS/TLR4 axis inflammatory response by down regulating the serum LPS and TLR4/NF-κB inflammatory pathway in kidney, thus promoting the excretion of uric acid in kidney. CONCLUSION: Chicory intervention ameliorated HUA via modulating the imbalance of gut microbiota and suppressing LPS/TLR4 axis inflammatory reaction in quail model, which may be a promising candidate for hyperuricemia-relieving properties.
背景：高嘌呤饮食可导致肠道菌群紊乱，这与高尿酸血症（HUA）的发生密切相关。同时，HUA 的发展常伴有肾脏损伤。菊苣作为一种天然药物，具有显著的降尿酸作用。然而，其具体机制是否与肠道菌群的调节和肾脏损伤有关尚不清楚。
方法：采用高嘌呤饮食诱导的高尿酸血症鹌鹑模型，将鹌鹑分为对照组（CON）、模型组（MOD）和模型加菊苣高、中、低剂量组。通过检测血清和粪便中的尿酸水平来评价菊苣的促尿酸排泄作用。同时，采用苏木精和伊红（HE）染色观察肠、肾形态，采用定量实时聚合酶链反应（qPCR）和蛋白质印迹法检测肠道屏障连接蛋白 Occludin、Claudin-1 的表达。此外，通过分析肠道菌群 16S rRNA 扩增子和蛋白质印迹法及酶联免疫吸附试验（ELISA）检测肾脏 LPS/TLR4 轴炎症反应的变化来阐明潜在机制。
结果：结果表明，菊苣干预后血清尿酸水平显著降低，粪便尿酸水平明显增加。此外，菊苣可以修复肠道黏膜损伤，提高肠道屏障通透性。此外，16S rRNA 测序分析发现，菊苣通过增加益生菌菌群（双歧杆菌、肠杆菌科）和减少致病菌群（螺旋杆菌科）来恢复肠道菌群。此外，研究还发现，菊苣通过下调血清 LPS 和 TLR4/NF-κB 炎症通路，降低肾脏 LPS/TLR4 轴炎症反应，从而促进肾脏尿酸排泄，减轻炎症反应。
结论：菊苣干预通过调节肠道菌群失衡和抑制鹌鹑模型中 LPS/TLR4 轴炎症反应改善 HUA，可能是一种有前途的降尿酸候选药物。
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