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

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]...

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Bibliographic Details
Published in:PeerJ (San Francisco, CA) CA), 2021-03, Vol.9, p.e10973
Main Authors: Kim, Hyun Jong, Park, Seorin, Shin, Hui Young, Nam, Yu Ran, Lam Hong, Phan Thi, Chin, Young-Won, Nam, Joo Hyun, Kim, Woo Kyung
Format: Article
Language:English
Subjects:
Calcium channels
Cytokines
Immunotherapy
Potassium channels
T cells
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Summary: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.sub.v 1.3 and K.sub.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 IC.sub.50 value was 1.27 ± 1.144 [micro]M. K.sub.v 1.3 was suppressed by 41.38 ± 6.191% at 3 [micro]M, and K.sub.Ca 3.1 was suppressed by 51.16 ± 5.385% at 3 [micro]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.
ISSN:2167-8359
2167-8359
DOI:10.7717/peerj.10973