Studies on the Absorption of Schisandra chinensis and Its Pharmacological Effects on Gut Motility and Visceral Sensation.

摘要

Schisandra chinensis, which is named "Wu-Wei-Zi" in Chinese Pin Yin, is widely used in Chinese medicine as an astringent, tonic and sedative agent. Dibenzo[a,c]-cyclooctadiene lignans are the major components of this herb. In the present study, the chemical constituents of S. chinensis were first characterized. A HPLC-DAD method was developed and validated for quantitative analysis of four major Schisandra lignans, namely, schisandrin (SCH-1), gomisin A (SCH-2), deoxyschisandrin (SCH-3) and gamma-schisandrin (SCH-4), in the aqueous and ethanolic extracts of S. chinensis. The ethanolic extract contains higher amount of lignan components than aqueous extract. The HPLC method has also been employed to obtain chromatographic fingerprintings to distinguish S. chinensis from a related species, S. sphenanthera..;With the aid of HPLC-DAD-MS for qualitative and quantitative analyses, the absorption of S. chinensis in the rat everted gut sac and human Caco-2 monolayer in vitro models have been profiled. Fifteen Schisandra lignans were identified as the major absorbable components of S. chinensis in these models. Transport study on SCH-1 has shown a passive diffusion pathway with high permeability. In an in vivo study, metabolites of Schisandra lignans could be found in rat plasma after a single oral administration of S. chinensis extract. The plasma pharmacokinetics of S. chinensis in rats was further evaluated using simultaneous quantification of four representative Schisandra lignans (SCH-1, SCH-2, SCH-3 and SCH-4).;The modulatory effects of both S. chinensis extracts and four major lignans on intestinal motility were evaluated using in vitro intestinal motility assays. The tested compounds induced relaxation on guinea pig ileum contracted by acetylcholine, serotonin and electrical field stimulation, as well as on rat colon with spontaneous contractility. While SCH-3 was most potent in inhibiting sensorimotor response in guinea pig ileum, SCH-1 displayed the highest potency of inhibition on spontaneous contraction of rat colon.;The relaxant effect on rat colon induced by SCH-1 has been demonstrated to involve two or more non-adrenergic non-cholinergic mediators. Nitric oxide was likely to be one of the inhibitory transmitters that involved cGMP-dependent pathways, whereas the non-nitrergic component was apamin-sensitive, but probably excluded vasoactive intestinal peptide (VIP) and adenosine.;In an irritable bowel syndrome (IBS) rat model, S. chinensis reversed the exaggerated visceral nocicptive responses (judged by abdominal withdrawal reflex and electromyographic measurement) to colorectal distension induced by neonatal maternal separation. Relief of visceral hypersensitivity by S. chinensis could be related to the decrease of elevated 5-HT level and the reduction in 5-HT3 receptor expression in colon.;In summary, given the modulatory effects on intestinal motility and visceral sensation, Schisandra chinensis would be potentially useful for the treatment of relieving diarrhea and visceral pain symptoms in IBS patients. Schisandra lignans, the major absorbable components, can be regarded as the active ingredients in S. chinensis for the potential treatment of IBS.