Drug Design, Development and Therapy (Feb 2022)
α-Mangostin Treats Early-Stage Adjuvant-Induced Arthritis of Rat by Regulating the CAP-SIRT1 Pathway in Macrophages
Abstract
Wen-Gang Chen,1,* Sa-Sa Zhang,1– 3,* Shu Pan,1– 3 Zhong-Fang Wang,1 Jin-Ying Xu,1 Xue-He Sheng,1 Qin Yin,1,2 Yi-Jin Wu1,3 1Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China; 2Graduate School, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China; 3Xin’An Medicine Research Center, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Yin; Yi-Jin Wu, Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China, Tel +86 13905530299 ; +86 17318531920, Email [email protected]; [email protected]: 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.Methods: 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 α 7 nicotinic cholinergic receptor (α 7nAChR) 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.Results: 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 α 7nAChR and SIRT1. Meanwhile, MG inhibited nuclear factor-κB (NF-κB)-mediated inflammation by activating the CAP-SIRT1 pathway in macrophages.Conclusion: 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.Keywords: α-mangostin, rheumatoid arthritis, choline anti-inflammatory pathway, silent information regulator 1, macrophages
