Inhibitory effects of α -Mangostin on T cell cytokine secretion via ORAI1 calcium channel and K + channels inhibition

PeerJ

article

Phan Thi Lam Hong¹  Young-Won Chin³  Joo Hyun Nam¹  Woo Kyung Kim²  Hyun Jong Kim¹  Seorin Park¹  Hui Young Shin¹  Yu Ran Nam² 

[1] Department of Physiology, Dongguk University College of Medicine;Channelopathy Research Center ,(CRC), College of Medicine, Dongguk University;College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University;Department of Internal Medicine Graduate School of Medicine, Dongguk University

关键词: α-Mangostin;    Ion channel;    ORAI1;    KCNN4;    Calcium signaling;    CD4+ T cell;    Potassium channel;    Calcium channel;   

DOI  :  10.7717/peerj.10973

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundAs one of the main components of mangosteen (Garcinia mangostana), a tropical fruit, α-mangostin has been reported to have numerous pharmacological benefits such as anti-cancer, anti-inflammatory, and anti-allergic effects through various mechanisms of action. The effects of α-mangostin on intracellular signaling proteins is well studied, but the effects of α-mangostin on ion channels and its physiological effects in immune cells are unknown. Generation of intracellular calcium signaling is a fundamental step for T cell receptor stimulation. This signaling is mediated not only by the ORAI1 calcium channel, but also by potassium ion channels, which provide the electrical driving forces for generating sufficient calcium ion influx. This study investigated whether α-mangosteen suppress T cell stimulation by inhibiting ORAI1 and two kinds of potassium channels (Kv1.3 and KCa3.1), which are normally expressed in human T cells.MethodsThis study analyzed the inhibitory effect of α-mangostin on immune cell activity via inhibition of calcium and potassium ion channels expressed in immune cells.Resultsα-mangostin inhibited ORAI1 in a concentration-dependent manner, and the IC50 value was 1.27 ± 1.144 µM. Kv1.3 was suppressed by 41.38 ± 6.191% at 3 µM, and KCa3.1 was suppressed by 51.16 ± 5.385% at 3 µM. To measure the inhibition of cytokine secretion by immune cells, Jurkat T cells were stimulated to induce IL-2 secretion, and α-mangostin was found to inhibit it. This study demonstrated the anti-inflammatory effect of α-mangostin, the main component of mangosteen, through the regulation of calcium signals.

【 授权许可】

CC BY