Inhibitory effect of schisandrin on spontaneous contraction of isolated rat colon

Jiaming Yang,Chun-Tao Che,Paul S.P Ip,John H.K Yeung

doi:10.1016/j.phymed.2011.02.014

Abstract

This study examined the effect of schisandrin, one of the major lignans isolated from Schisandra chinensis, on spontaneous contraction in rat colon and its possible mechanisms. Schisandrin produced a concentration-dependent inhibition (EC₅₀=1.66 μM) on the colonic spontaneous contraction. The relaxant effect of schisandrin could be abolished by the neuronal Na+ channel blocker tetrodotoxin (1 μM) but not affected by propranolol (1 μM), phentolamine (1 μM), atropine (1 μM) or nicotine desensitization, suggesting possible involvement of non-adrenergic non-cholinergic (NANC) transmitters released from enteric nerves. N(ω)-nitro-l-arginine methyl ester (100-300 μM), a nitric oxide synthase inhibitor, attenuated the schisandrin response. The role of nitric oxide (NO) was confirmed by an increase in colonic NO production after schisandrin incubation, and the inhibition on the schisandrin responses by soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-α]-quinoxalin-1-one (1-30 μM). Non-nitrergic NANC components may also be involved in the action of schisandrin, as suggested by the significant inhibition of apamin on the schisandrin-induced responses. Pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate (100 μM), a selective P2 purinoceptor antagonist, markedly attenuated the responses to schisandrin. In contrast, neither 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A₁ receptors, nor chymotrypsin, a serine endopeptidase, affected the responses. All available results have demonstrated that schisandrin produced NANC relaxation on the rat colon, with the involvement of NO and acting via cGMP-dependent pathways. ATP, but not adenosine and VIP, likely plays a role in the non-nitrergic, apamin-sensitive component of the response.

Highlights

Schisandra chinensis (Turcz.) Baill. (Schisandraceae) is a well-known medicinal herb in China and East Asia
Our preliminary results have shown that the aqueous and ethanol extracts of S. chinensis caused concentration-dependent inhibition on the spontaneous contraction of isolated rat colon, and schisandrin is a major lignan constituent (Halstead et al, 2007)
Schisandrin caused an acute relaxation within seconds upon sample administration, and the inhibitory responses on spontaneous contraction of proximal and distal colon segments were similar in magnitude

Summary

Introduction

Schisandra chinensis (Turcz.) Baill. (Schisandraceae) is a well-known medicinal herb in China and East Asia. The dried ripe fruits are used as a tonic and astringent in traditional Chinese medicine (Chinese Pharmacopoeia, 2005), and a number of Schisandra products or combinations are commercially available as dietary supplements in the Western countries. S. chinensis found applications in the treatment of hepatitis due to its liver-protective effects (Ip et al, 1996; Pan et al, 2008). This herbal drug is rich in lignan compounds, and it has been suggested that they contribute to the anti-oxidant, hepatic-protective and cancerpreventive effects of the crude drug (Opletal et al, 2004; Panossian & Wikman, 2008). S. chinensis extracts and gomisin A were shown to produce vasorelaxant effect on rat thoracic aorta via endothelium-dependent and endotheliumindependent pathways (Rhyu et al, 2006; Park et al, 2007; Park et al, 2009)

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