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

Abstract

Background. As one of the main components of mangosteen (Garcinia mangostana), a tropical fruit, alpha-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 alpha-mangostin on intracellular signaling proteins is well studied, but the effects of alpha-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 alpha-mangosteen suppress T cell stimulation by inhibiting ORAI1 and two kinds of potassium channels (K(v)1.3 and K(Ca)3.1), which are normally expressed in human T cells. Methods. This study analyzed the inhibitory effect of alpha-mangostin on immune cell activity via inhibition of calcium and potassium ion channels expressed in immune cells. Results. alpha-mangostin inhibited ORAI1 in a concentration-dependent manner, and the IC50 value was 1.27 +/- 1.144 mu M. K(v)1.3 was suppressed by 41.38 +/- 6.191% at 3 mu M, and K(Ca)3.1 was suppressed by 51.16 +/- 5.385% at 3 mu M. To measure the inhibition of cytokine secretion by immune cells, Jurkat T cells were stimulated to induce IL-2 secretion, and alpha-mangostin was found to inhibit it. This study demonstrated the anti-inflammatory effect of alpha-mangostin, the main component of mangosteen, through the regulation of calcium signals.