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

Pharm Biol. 2018 Dec;56(1):559-566. doi: 10.1080/13880209.2018.1492000.

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.

Keywords: Ca channels; Cholinergic; Wei-Chang-An pill; interstitial cells of Cajal; neostigmine; nitric oxide.

MeSH terms

  • Animals
  • Calcium Channel Blockers / isolation & purification
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / physiology
  • Dose-Response Relationship, Drug
  • Gastric Emptying / drug effects
  • Gastric Emptying / physiology
  • Gastrointestinal Motility / drug effects*
  • Gastrointestinal Motility / physiology
  • Mice
  • Muscarinic Antagonists / isolation & purification
  • Muscarinic Antagonists / pharmacology*
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / physiology
  • Organ Culture Techniques
  • Parasympatholytics / isolation & purification
  • Parasympatholytics / pharmacology*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Receptors, Muscarinic / physiology
  • Thymelaeaceae*

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Muscarinic Antagonists
  • Parasympatholytics
  • Plant Extracts
  • Receptors, Muscarinic
  • Nitric Oxide

Grants and funding

This work was supported by Special Financial Grant from the China Postdoctoral Science Foundation (No. 2015T81140) and National Natural Science Foundation of China Youth Fund Project (No. 81503467).