Abstract：
Gallic acid (GA) has been found by a large number of studies to have pharmacological effects such as antioxidant and anti-inflammatory properties. However, the underlying therapeutic mechanisms are not fully understood.. Studies have shown that altering the intestinal flora affects host metabolism and effectively mediates the development of synovitis. The aim of this study was to explore the pharmacological effects of GA in the treatment of synovial inflammation and anti-synovial fibrosis in knee osteoarthritis (KOA) and the underlying mechanisms by macrogenomics combined with off-target metabolomics. We established a synovitis model via in vivo and in vitro experiments to observe the effect of GA intervention on synovitis. Moreover, we collected serum and feces from rats and analyzed the changes in intestinal flora by macro-genome sequencing and the changes in metabolites in the serum by untargeted metabolomics. We found that GA reduced the levels of IL-1β, IL-6, and TNF-α, and decreased the protein expression levels of α-SMA, TGF-β, and Collagen I in synovial tissues and cells, and the composition and function of the intestinal flora were similarly altered. Combined with macrogenomic pathway enrichment analysis and metabolic pathway enrichment analysis, these findings revealed that GA impacts Bacteroidia and Muribaculaceae abundance, and via the following metabolic pathways: sphingolipid metabolism, glycerophospholipid metabolism, and arginine biology.to ameliorate synovial inflammation and fibrosis in KOA. The therapeutic effect of GA on KOA synovitis and fibrosis is partly attributed to the alleviation of metabolic disorder and the rebalancing of the intestinal flora. These results provides a rationale for the therapeutic application of GA in the treatment of synovitis.
摘要：
没食子酸(GA)已被年夜量研讨发明具有抗氧化和抗炎等药理作用。然而,潜在的治疗机制尚不完全清楚..研究表明，改变肠道菌群影响宿主代谢并有效介导滑膜炎的发展。本研究旨在通过大基因组学结合脱靶代谢组学探讨GA治疗膝关节骨性关节炎(KOA)滑膜炎性和抗滑膜纤维化的药理作用及其机制。我们通过体内和体外实验建立滑膜炎模型，观察GA干预对滑膜炎的影响。此外，我们收集了大鼠的血清和粪便，并通过宏基因组测序分析了肠道菌群的变化，并通过非靶向代谢组学分析了血清中代谢物的变化。我们发现GA降低了IL-1β的水平，IL-6和TNF-α,降低了α-SMA的蛋白表达水平,TGF-β,滑膜组织和细胞中的胶原蛋白I，肠道菌群的组成和功能也发生了类似的改变。结合大基因组途径富集分析和代谢途径富集分析,这些发现表明，GA影响拟杆菌属和Muribaculaceae的丰度，并通过以下代谢途径：鞘脂代谢，甘油磷脂代谢，和精氨酸生物学。改善KOA滑膜炎症和纤维化。GA对KOA滑膜炎和纤维化的治疗作用部分归因于代谢紊乱的缓解和肠道菌群的重新平衡。这些结果为GA在滑膜炎治疗中的治疗应用提供了理论基础。
