Effects of Sho-ju-sen, a Japanese herbal medicine, on catechoamine secretion induced by acetylcholine in cultured bovine adrenal medullary cells

Abstract

Sho-ju-sen is a Japanese herbal medicine which has been used as a nourishing tonic. It is composed of a water extract of Kumazasa leaves (Sasa kurinensis Makino et Sibata) and ethanol extracts of Japanese red pine needles (Pinus densiflora Sieb. Et Zucc) and ginseng roots (Panax ginseng C. A. Meyer). Previous studies showed that Sho-ju-sen has antidepressant and anxiolytic effects in mice (Phytother Res., 15: 142-147, 2001 and 18: 173-176, 2004). Here we report that the effects of Sho-ju-sen on catecholamine secretion in cultured bovine adrenal medullary cells. Adrenal medullary cells have provided a good material for the detailed analysis of a drug's actions on catecholamine secretion and have been used as a model of the sympathetic neurons. We found that Sho-ju-sen (0.5 - 1 %) and extract of Kumazasa leaves (0.5-1 %), but not ethanol extract of Japanese red pine needles or ginseng roots, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, Sho-ju-sen (0.5 - 1 %) directly inhibited Na+ current evoked by acetylcholine. Sho-ju-sen (0.3 - 1 %) also inhibited catecholamine secretion induced by veratridine, an activator of voltage-dependent Na+ channels, but not by 56 mM K+ which depolarizes cell membranes. The present findings demonstrate that Sho-ju-sen inhibits acetylcholine- and veratridine-induced catecholamine secretion by suppression of nicotinic acetylcholine receptor-ion channels and voltage-dependent Na+ channels in adrenal medulla cells and probably sympathetic neurons, and also suggest that Sho-ju-sen has an anti-stress effect.