γ-Mangostin increases serotonin 2A/2C, muscarinic, histamine and bradykinin receptor mRNA expression.

γ-Mangostin is a xanthone found in the fruit hulls of Garcinia mangostana L., which have long been used in Southeast Asia as a traditional medicine for the treatment of abdominal pain, dysentery, wound infections, fever and convulsions. Recent studies have revealed that γ-mangostin exhibits a variety of pharmacological activities, including serotonin 2 (5-HT(2)) receptor antagonism, anti-inflammatory effects and analgesic effects. To explore the mechanism of γ-mangostin responsible for these pharmacological activities, especially its effects on some related receptors, we investigated the effects of γ-mangostin on 5-HT(2), histamine (H(1)) and bradykinin (BK(2)) receptor gene expression in neuroblastoma (NG 108-15) cells in vitro. Additionally, to extend the study of the pharmacological properties, we examined the effect of γ-mangostin on the muscarinic (M(4)) receptor. NG 108-15 cells were cultured in vitro and treated with γ-mangostin or a 5-HT(2) receptor antagonist (either imipramine or ketanserin). Then, the levels of mRNA for 5-HT(2A/2C) receptors were evaluated by semi-quantitative RT-PCR. The preventive effect of serotonin on the enhancement effects was also revealed. Additionally, the effects of γ-mangostin on the muscarinic, histamine and bradykinin receptors were determined. Chronic application of γ-mangostin at a concentration of 0.1 μM induced a significant increase in the level of 5-HT(2A/2C) receptor mRNA. These effects were prevented by serotonin. Moreover, γ-mangostin up-regulated the M(4), H(1) and BK(2) receptors. The ability of γ-mangostin to enhance the expression of 5-HT(2A/2C), muscarinic, histamine and bradykinin receptor mRNA suggests that this compound has antagonistic effects. These pharmacological properties may partly account for the benefits of using mangosteen in the treatment of inflammation, pain and neuropsychiatric symptoms.