Spasmolytic activity of Aquilariae Lignum Resinatum extract on gastrointestinal motility involves muscarinic receptors, calcium channels and NO release

Abstract

Context: Aquilariae Lignum Resinatum (ALR), the dry rhizome of Aquilaria agallocha R. (Thymelaeaeeae), has been widely used to treat emesis, stomachache and gastrointestinal dysfunction. Objective: This study evaluates the effects of ALR methanol extract on gastrointestinal motility (GIM) and possible mechanisms of the action involved. Materials and methods: In vivo, the study evaluated the effects of ALR (200–800 mg/kg) on gastric emptying and small intestinal motility in normal and neostigmine-induced adult KM mice. The in vitro effects of ALR (0.2–1.6 mg/mL) on GIM were performed on isolated jejunum of Wistar rats, pretreated with acetylcholine (ACh), KCl, CaCl₂, and pre-incubation with l-NAME (a selective inhibitor of the nitric oxide synthase). Results: In vivo, ALR (800 mg/kg) decreased gastric emptying (70.82 ± 9.81%, p < 0.01, compared with neostigmine group 91.40 ± 7.81%), small intestinal transit (42.82 ± 3.82%, p < 0.01, compared with neostigmine group 85.53 ± 5.57%). In vitro, ALR concentration dependently decreased the contractions induced by ACh (10⁻⁵ M) and KCl (60 mM) with respective EC₅₀ values of 0.35 and 0.32 mg/mL. The Ca²⁺ concentration–response curves were shifted by ALR to the right, similar to that caused by verapamil (the positive). The spasmolytic activity of ALR was inhibited by pre-incubation with l-NAME. Discussion and conclusions: ALR played a spasmolytic role in GIM, which is probably mediated through inhibition of muscarinic receptors, blockade of Ca²⁺ influx and NO release. This is the first study presenting a comprehensive description of the effects of ALR on GIM.