Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, People's Republic of China.
Graduate School, Wannan Medical College, Wuhu, 241000, Anhui, People's Republic of China.
Drug Des Devel Ther. 2022 Feb 27;16:509-520. doi: 10.2147/DDDT.S348836. eCollection 2022.
Studies have found that α-mangostin (MG) can relieve experimental arthritis by activating cholinergic anti-inflammatory pathway (CAP). It affects the polarization of macrophages and the balance of related immune cell subpopulations, but the specific mechanism is still unclear. It has been found that silent information regulator 1 (SIRT1) is closely related to macrophage activity. The purpose of this study is to explore the mechanism of MG intervening in macrophage polarization during treatment of early adjuvant-induced (AIA) rats through the CAP-SIRT1 pathway.
We investigated the polarization of M1 macrophages and the differentiation of Th1 in AIA rats by flow cytometry. Activity of acetylcholinesterase (AChE) and the level of nicotinic adenine dinucleotide (NAD+) in serum were also detected, and immunohistochemical was used to detect the levels of α7 nicotinic cholinergic receptor (α7nAChR) and SIRT1. Then in macrophages, the molecular mechanism of MG regulating the abnormal activation of macrophages in rats with early AIA through the CAP-SIRT1 pathway was studied.
MG can significantly inhibit the polarization of M1 macrophages and the differentiation of Th1 in AIA rats in the acute phase of inflammation. MG can significantly inhibit the activity of AChE and increase the level of NAD+, thereby further up-regulated the expression levels of α7nAChR and SIRT1. Meanwhile, MG inhibited nuclear factor-κB (NF-κB)-mediated inflammation by activating the CAP-SIRT1 pathway in macrophages.
In summary, the stimulation of MG induced CAP activation, which up-regulated SIRT1 signal, and thereby inhibited M1 polarization through the NF-κB pathway, and improved the pathological immune environment of early-stage AIA rats.
研究发现，α-倒捻子素（MG）可通过激活胆碱能抗炎途径（CAP）缓解实验性关节炎。它影响巨噬细胞的极化和相关免疫细胞亚群的平衡，但具体机制尚不清楚。已经发现沉默信息调节因子 1（SIRT1）与巨噬细胞活性密切相关。本研究旨在通过 CAP-SIRT1 途径探讨 MG 在治疗早期佐剂诱导（AIA）大鼠过程中干预巨噬细胞极化的机制。
我们通过流式细胞术研究了 AIA 大鼠 M1 巨噬细胞的极化和 Th1 的分化。还检测了血清中乙酰胆碱酯酶（AChE）的活性和烟酰胺腺嘌呤二核苷酸（NAD+）的水平，并通过免疫组织化学检测了α7 型烟碱型乙酰胆碱受体（α7nAChR）和 SIRT1 的水平。然后，在巨噬细胞中，研究了 MG 通过 CAP-SIRT1 途径调节早期 AIA 大鼠巨噬细胞异常激活的分子机制。
MG 可显著抑制炎症急性期 AIA 大鼠 M1 巨噬细胞的极化和 Th1 的分化。MG 可显著抑制 AChE 的活性并增加 NAD+的水平，从而进一步上调α7nAChR 和 SIRT1 的表达水平。同时，MG 通过激活 CAP-SIRT1 通路抑制核因子-κB（NF-κB）介导的炎症反应。
综上所述，MG 的刺激诱导 CAP 激活，上调 SIRT1 信号，从而通过 NF-κB 通路抑制 M1 极化，改善早期 AIA 大鼠的病理性免疫环境。
