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.

Underlying Mechanisms of Anti-spasmodic, Antidiarrheal, Antioxidant and Acute Toxicity Assessments of Aqueous Extract of Mentha Suaveolens Ehrh and its Fourier Transform Infra-red Spectroscopy Analysis

“…5). Our data are similar with many others studies, confirming the implication of NO/cGMP pathway in spasmolytic effect of plant products reported [45][46][47].…”

Aqueous Tuber Extracts of Tylosema fassoglense (Kotschy ex Schweinf.) Torre and Hillc. (Fabaceae). Possess Significant In-Vivo Antidiarrheal Activity and Ex-Vivo Spasmolytic Effect Possibly Mediated by Modulation of Nitrous Oxide System, Voltage-Gated Calcium Channels, and Muscarinic Receptors

“…The freeze-dried extracts of TFG possessed significant effects on the peristaltic index at all the doses tested but only exhibited a significant effect on gastric emptying rate at the highest doses tested in the neostigmine-induced gastrointestinal motility experiment. Neostigmine is an indirect cholinergic agonist that inhibits the activity of acetylcholinesterase enzyme thus elevating the levels of endogenous acetylcholine to a mild cholinergic toxidrome at a dose of 0.1–0.05 mg/kg ( Li et al, 2018 ). The observed overall effect is as result of an increased enteric cholinergic activity on muscarinic receptors where activation of M2 receptors lowers cytosolic cAMP levels and thus increased calcium sensitization while M3 activation increases cytosolic calcium ions ( Li et al, 2018 ).The net effect is increased phosphorylation of myosin light chain and subsequent increased force of contraction leading to increased gastrointestinal motility ( Fukata et al, 2001 ).…”

“…The animals were acclimatized for two weeks before the commencement of the experiments. The procedures used in this study are similar to those used in Li et al, (2018) .…”

“…The jejunal segments were then incubated with the respective receptor blockers for 2 min. The incubation period was also 2 min for methylene blue but 20 min for L-NAME as described by Li et al (2018) . Tracings of 3 min were recorded after incubation with receptor/enzyme blocker then followed by a 10-min recording upon addition of the respective TFG concentrations.…”

Effects of Chaihu-Shugan-San on Small Intestinal Interstitial Cells of Cajal in Mice

“…2) Among various diseases, an estimated 51% of patients have gastrointestinal (GI) disorders and 10% of alternative medicines are being used for digestive symptoms. 3) These GI conditions have been reduced the quality of human life and increased the cost of maintaining health. 4) However, these various available drugs treatment for these diseases are chemical drugs and these chemical drugs have a large number of adverse effects.…”