Background: Studies have shown that α-mangostin (MG) could exert anti-rheumatic effects in vivo by restoring immunity homeostasis, and have indicated that activation of the choline anti-inflammatory pathway (CAP) may contribute to this immunomodulatory property. The current study was designed to further investigate the effects of MG on the CAP in peripheral immune cells and clarify its relevance to the potential anti-rheumatic actions.
Methods: The catalytic activity of acetylcholinesterase (AChE) and expression of α 7-nicotinic cholinergic receptor (α 7nAChR) in peripheral blood mononuclear cells (PBMCs) from rats with collagen-induced arthritis (CIA) or human volunteers were evaluated after MG treatment. Consequent influences on the immune environment were assessed by flow cytometry and ELISA analyses. Indirect effects on joints resulting from these immune changes were studied in a co-culture system comprised of fibroblast-like synoviocytes (FLSs) and PBMCs.
Results: MG promoted α 7nAChR expression in PBMCs both in vivo and in vitro, and inhibited the enzymatic activity of AChE simultaneously. Activation of the CAP was accompanied by a significant decrease in Th17 cells (CD4⁺IL-17A⁺), while no obvious changes concerning the distribution of other T-cell subsets were noticed upon MG treatment. Meanwhile, MG decreased the secretion of TNF-α and IL-1β under inflammatory conditions. PBMCs from MG-treated CIA rats lost the potential to stimulate NF-κB activation and pro-inflammatory cytokine production of FLSs in the co-culture system.
Conclusion: Overall, the evidence suggested that MG can improve the peripheral immune milieu in CIA rats by suppressing Th17-cell differentiation through CAP activation, and achieve remission of inflammation mediated by FLSs.



中文翻译：

---

外周免疫细胞中胆碱能抗炎通路的激活参与 α-山竹素对大鼠胶原蛋白诱导的关节炎的治疗作用。

背景：研究表明，α-山竹素 (MG) 可通过恢复免疫稳态在体内发挥抗风湿作用，并表明胆碱抗炎途径 (CAP) 的激活可能有助于这种免疫调节特性。本研究旨在进一步研究 MG 对外周免疫细胞 CAP 的影响，并阐明其与潜在抗风湿作用的相关性。
方法：在 MG 治疗后评估了胶原诱导性关节炎 (CIA) 大鼠或人类志愿者外周血单个核细胞 (PBMC) 中乙酰胆碱酯酶 (AChE) 的催化活性和α 7-烟碱型胆碱能受体 (α 7nAChR) 的表达。通过流式细胞术和 ELISA 分析评估对免疫环境的后续影响。在由成纤维细胞样滑膜细胞 (FLS) 和 PBMC 组成的共培养系统中研究了这些免疫变化对关节的间接影响。
结果： MG在体内外均促进PBMCs中α7nAChR的表达，同时抑制AChE的酶活性。CAP 的激活伴随着 Th17 细胞（CD4 ⁺ IL-17A ⁺)，而在 MG 治疗后，其他 T 细胞亚群的分布没有明显变化。同时，MG在炎症条件下降低了TNF-α和IL-1β的分泌。来自 MG 治疗的 CIA 大鼠的 PBMCs 在共培养系统中失去了刺激 NF-κB 活化和 FLSs 促炎细胞因子产生的潜力。
结论：总体而言，有证据表明MG可通过CAP激活抑制Th17细胞分化来改善CIA大鼠的外周免疫环境，并实现FLS介导的炎症缓解。