Antispasmodic Effect of Asperidine B, a Pyrrolidine Derivative, through Inhibition of L-Type Ca2+ Channel in Rat Ileal Smooth Muscle.

Acharaporn Duangjai,Chutima Srimaroeng,Vatcharin Rukachaisirikul,Chatchai Muanprasat,Yaowapa Sukpondma

doi:10.3390/molecules26185492

Abstract

Antispasmodic agents are used for modulating gastrointestinal motility. Several compounds isolated from terrestrial plants have antispasmodic properties. This study aimed to explore the inhibitory effect of the pyrrolidine derivative, asperidine B, isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178, on spasmodic activity. Isolated rat ileum was set up in an organ bath. The contractile responses of asperidine B (0.3 to 30 µM) on potassium chloride and acetylcholine-induced contractions were recorded. To investigate its antispasmodic mechanism, CaCl2, acetylcholine, Nω-nitro-l-arginine methyl ester (l-NAME), nifedipine, methylene blue and tetraethylammonium chloride (TEA) were tested in the absence or in the presence of asperidine B. Cumulative concentrations of asperidine B reduced the ileal contraction by ~37%. The calcium chloride and acetylcholine-induced ileal contraction was suppressed by asperidine B. The effects of asperidine B combined with nifedipine, atropine or TEA were similar to those treated with nifedipine, atropine or TEA, respectively. In contrast, in the presence of l-NAME and methylene blue, the antispasmodic effect of asperidine B was unaltered. These results suggest that the antispasmodic property of asperidine B is probably due to the blockage of the L-type Ca2+ channel and is associated with K+ channels and muscarinic receptor, possibly by affecting non-selective cation channels and/or releasing intracellular calcium.

Highlights

The results showed that neither nifedipine, asperidine B nor nifedipine combined with asperidine exhibited anan inhibitory effect on ileum contraction induced combined with asperidine exhibited inhibitory effect on the ileum contraction combined with asperidine exhibited inhibitory effect onthe the ileum contraction in-inby
Tween methylene blue and KCl plus methylene blue. These results indicated that the relaxation effects of asperidine B may not involve the nitric oxide (NO)–GC–cyclic guanosine monophosphate (cGMP) pathway
All data are expressed as mean ± standard error of the mean (SEM) for each group of experiments (n = 5–9 for each set of experiments) and were analyzed by using a one-way analysis of variance (ANOVA) for repeated measures, and the significance of differences between groups were assessed by the Student’s t-test; p-values of less than 0.05 were considered significant. These findings indicate that asperidine B possesses antispasmodic activities mediated predominantly through the blockade of L-type Ca2+ channel and K+ channels

Summary

Introduction

Antispasmodic compounds are widely used to control anxiety and musculoskeletal tension [1], and they are especially used for reducing intestinal motility in gastrointestinal smooth muscle spasms. Gastrointestinal motility disorders are described by abnormal intestinal contractions, including achalasia, non-achalasia esophageal motility disorders, dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, irritable bowel syndrome (IBS) and chronic constipation [2]. Abnormal intestinal contractions lead to impaired quality of life and high healthcare costs. Several drugs and alternative medicines have been proposed to manage intestinal motility disorders by intervening in the underlying pathophysiology of these disorders

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