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  • Title: In vitro inhibition of adrenal catecholamine secretion by steroidal metabolites of ginseng saponins.
    Author: Tachikawa E, Kudo K, Hasegawa H, Kashimoto T, Sasaki K, Miyazaki M, Taira H, Lindstrom JM.
    Journal: Biochem Pharmacol; 2003 Dec 01; 66(11):2213-21. PubMed ID: 14609746.
    Abstract:
    We reported previously that the protopanaxatriol saponins in Panax ginseng greatly reduce the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh). However, protopanaxadiol saponins showed only slight inhibitory effects. Recent studies have demonstrated that oligosaccharides connected to the hydroxyl groups of the aglycone in ginseng saponins (ginsenosides) are in turn hydrolyzed in the digestive tract and absorbed into the circulation following oral administration of ginseng. Therefore, the present study was performed to investigate the effects of the major ginsenoside metabolites (M1, M2, M3, M4, M5, M11, and M12) on catecholamine secretion. All of these metabolites were shown to be potent inhibitors of ACh-evoked secretion, and M4 was the most effective. M4 blocked not only the ACh-induced Na(+) influx into the chromaffin cells but also the ACh-induced inward current into Xenopus oocytes expressing human alpha 3 beta 4 neuronal nicotinic ACh receptors. M4 reduced the secretion induced by high K(+), an activator of voltage-sensitive Ca(2+) channels, to a much lesser extent than that evoked by ACh. M1, M2, M3, M5, and M12 are protopanaxadiol saponin-derived metabolites. Therefore, these results imply that the protopanaxadiol saponins are prodrugs, and they show more potent inhibitory activity following metabolism in the digestive tract. The results further suggest that the metabolites act on nicotinic ACh receptors, blocking Na(+) influx through the receptors, and consequently reduce the catecholamine secretion from bovine adrenal chromaffin cells. The inhibitory effect of ginsenoside metabolites is probably one of the mechanisms of action responsible for the pharmacological effects of ginseng.
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