Prolonged administration of total glucosides of paeony improves intestinal immune imbalance and epithelial barrier damage in collagen-induced arthritis rats based on metabolomics-network pharmacology integrated analysis

作者：Rui Xu, Jine Peng, Zhe Ma, Kaili Xie, Meijing Li, Qi Wang, Xiaomeng Guo, Nan Nan, Sihui Wang, Jing Li, Jingjing Xu, Muxin Gong · 发表于：Frontiers in Pharmacology · 年份：2023 · DOI：10.3389/fphar.2023.1187797 · 被引用次数：10 · 研究领域：Ginseng Biological Effects and Applications、Rheumatoid Arthritis Research and Therapies、Immune Cell Function and Interaction

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and joint damage with complex pathological mechanisms. In recent years, many studies have shown that the dysregulation of intestinal mucosal immunity and the damage of the epithelial barrier are closely related to the occurrence of RA. Total glucosides of paeony (TGP) have been used clinically for the treatment of RA in China for decades, while the pharmacological mechanism is still uncertain. The purpose of this study was to investigate the regulatory effect and mechanism of TGP on intestinal immunity and epithelial barrier in RA model rats. The results showed that TGP alleviated immune hyperfunction by regulating the ratio of CD3 + , CD4 + and CD8 + in different lymphocyte synthesis sites of the small intestine, including Peyer’s patches (PPs), intraepithelial lymphocytes (IELs), and lamina propria lymphocytes (LPLs). Specially, TGP first exhibited immunomodulatory effects on sites close to the intestinal lumen (IELs and LPLs), and then on PPs far away from the intestinal lumen as the administration time prolonged. Meanwhile, TGP restores the intestinal epithelial barrier by upregulating the ratio of villi height (V)/crypt depth (C) and expression of tight junction proteins (ZO-1, occludin). Finally, the integrated analysis of metabolomics-network pharmacology was also used to explore the possible regulation mechanism of TGP on the intestinal tract. Metabolomics analysi...