Relaxant effects of Schisandra chinensis and its major lignans on agonists-induced contraction in guinea pig ileum

In this study, the herbal extracts of Schisandra chinensis were demonstrated to inhibit the contractions induced by acetylcholine (ACh) and serotonin (5-HT) in guinea pig ileum, and the 95% ethanol extract was more effective than the aqueous extract. Analysis with High Performance Liquid Chromatography (HPLC) indicated that schisandrin, schisandrol B, schisandrin A and schisandrin B were the major lignans of Schisandra chinensis, and the ethanol extract contained higher amount of these lignans than the aqueous extract. All four lignans inhibited the contractile responses to ACh, with EC20 values ranging from 2.2 +/- 0.4 mu M (schisandrin A) to 13.2 +/- 4.7 mu M (schisandrin). The effectiveness of these compounds in relaxing the 5-HT-induced contraction was observed with a similar magnitude. Receptor binding assay indicated that Schisandra lignans did not show significant antagonistic effect on muscarinic M3 receptor. In Ca2+-free preparations primed with ACh or KCl schisandrin A (50 mu M) attenuated the contractile responses to cumulative addition of CaCl2 by 37%. In addition, schisandrin A also concentration-dependently inhibited ACh-induced contractions in Ca2+-free buffer. This study demonstrates that Schisandra chinensis exhibited relaxant effects on agonist-induced contraction in guinea pig ileum, with schisandrin, schisandrol B, schisandrin A and schisandrin B being the major active ingredients. The antispasmodic action of schisandrin A involved inhibitions on both Ca2+ influx through L-type Ca2+ channels and intracellular Ca2+ mobilization, rather than specific antagonism of cholinergic muscarinic receptors. (C) 2011 Elsevier GmbH. All rights reserved.