Effects of triterpenoids from Poria cocos Wolf on the serotonin type 3A receptor-mediated ion current in Xenopus oocytes

Abstract

Poria cocos Wolf (P. cocos Wolf) is used to treat chronic gastritis, edema, nephrosis, gastric atony, acute gastroenteric catarrh, dizziness, emesis and vomiting. Triterpenoids are a class of natural compounds produced by P. cocos Wolf that contain acyclic 30-carbon precursors. In this study, we investigated the effect of triterpenoids (PA, Pachymic acid; DA, dehydroeburicoic acid; HA, 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid) on human 5-hydroxytryptamine 3A (5-HT 3A) receptor channel activity, which is one of the ligand-gated ion channel families. The two-electrode voltage-clamp technique was used to examine the 5-HT3A mediated current. The inhibitory effect of triterpenoids on 5HT-induced inward current (I 5-HT) occurred in a concentration dependent and reversible manner. Furthermore, the half-inhibitory concentrations (IC 50) of PA, DA and HA were 3.2 ± 0.2, 5.5 ± 0.6 and 1.4 ± 0.2 μM, respectively. This corresponded to an order of potency for the inhibition of I 5-HT in oocytes expressing human 5-HT 3A receptor of HA > PA > DA. Finally, inhibition of I 5HT by triterpenoids occurred in a non-competitive manner, while inhibition by HA and PA showed more voltage-dependency. Taken together, these results indicate that triterpenoids may regulate the expressed 5-HT 3A receptors in Xenopus oocytes. Furthermore, this regulation of the ligand-gated ion channel activity by triterpenoids may be one of the pharmacological actions of P. cocos Wolf. © 2009 Elsevier B.V. All rights reserved.