Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, People's Republic of China.
Department of Traditional Chinese Medicine, Yijishan Hospital of Wannan Medical College, Wuhu 241000, People's Republic of China.
Drug Des Devel Ther. 2020 May 22;14:1983-1993. doi: 10.2147/DDDT.S249865. eCollection 2020.
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.
The catalytic activity of acetylcholinesterase (AChE) and expression of α7-nicotinic cholinergic receptor (α7nAChR) 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.
MG promoted α7nAChR 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 (CD4IL-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.
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.
研究表明，α-倒捻子素（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 对周围免疫细胞中 CAP 的影响，并阐明其与潜在抗风湿作用的相关性。
用 MG 处理胶原诱导关节炎（CIA）大鼠或志愿者外周血单个核细胞（PBMC）后，评估其乙酰胆碱酯酶（AChE）的催化活性和α7 型烟碱型乙酰胆碱受体（α7nAChR）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。在由成纤维样滑膜细胞（FLS）和 PBMC 组成的共培养系统中研究这些免疫变化对关节的间接影响。
MG 促进了 PBMC 中α7nAChR 的表达，无论是在体内还是在体外，并同时抑制了 AChE 的酶活性。CAP 的激活伴随着 Th17 细胞（CD4IL-17A）的显著减少，而在 MG 处理时，其他 T 细胞亚群的分布没有明显变化。同时，MG 减少了 TNF-α和 IL-1β 在炎症条件下的分泌。来自 MG 处理的 CIA 大鼠的 PBMC 在共培养系统中丧失了刺激 NF-κB 激活和 FLS 产生促炎细胞因子的潜力。
总的来说，有证据表明，MG 通过激活 CAP 抑制 Th17 细胞分化，改善 CIA 大鼠的外周免疫环境，并实现由 FLS 介导的炎症缓解。
