Banha-sasim-tang improves gastrointestinal function in loperamide-induced functional dyspepsia mouse model

J Ethnopharmacol. 2019 Jun 28:238:111834. doi: 10.1016/j.jep.2019.111834. Epub 2019 Mar 30.

Abstract

Ethnopharmacological relevance: Banha-sasim-tang (BST; Hange-shashin-to in Kampo medicine; Banxia xiexin tang in traditional Chinese medicine) is a traditional Chinese harbal medicine that has been commonly used for gastrointestinal disorders.

Aim of the study: To investigate the pharmacological effects of BST, a standardized herbal drug, on main symptoms of functional dyspepsia including delayed gastric emptying, and underlying mechanisms of action in mouse model.

Methods and materials: Balb/C mice were pretreated with BST (25, 50, 100 mg/kg, po) or mosapride (3 mg/kg, po) for 3 days, and then treated with loperamide (10 mg/kg, ip) after 19 h fasting. A solution of 0.05% phenol red (500 μL) or 5% charcoal diet (200 μL) was orally administered, followed by scarifying and assessment of gastric emptying or gastro-intestinal motility. C-kit (immunofluorescence), nNOS (western blot) and gastric contraction-related gene expression were examined in stomach tissue.

Results: The loperamide injection substantially delayed gastric emptying, while the BST pretreatment significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of stomach-retained phenol red (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The BST pretreatment significantly tempered the loperamide-induced inactivation of c-kit and nNOS (p < 0.05 or 0.01) as well as the contraction-related gene expression, such as the 5HT4 receptor (5HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK). The BST pretreatment also significantly attenuated the alterations in gastro-intestinal motility (p < 0.01).

Conclusion: Our results are the first evidence of the prokinetic agent effects of Banha-sasim-tang in a loperamide-induced FD animal model. The underlying mechanisms of action may involve the modulation of peristalsis via activation of the interstitial cells of Cajal and the smooth muscle cells in the stomach.

Keywords: Banha sasim-tang; Functional dyspepsia; Gastric emptying; Gastrointestinal motility; Interstitials cells of Cajal.

MeSH terms

  • Animals
  • Anoctamin-1 / genetics
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Dyspepsia / chemically induced
  • Dyspepsia / drug therapy*
  • Dyspepsia / genetics
  • Dyspepsia / metabolism
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastrointestinal Motility / drug effects
  • Loperamide
  • Male
  • Mice, Inbred BALB C
  • Myosin-Light-Chain Kinase / genetics
  • Nitric Oxide Synthase Type I / metabolism
  • Receptors, Serotonin, 5-HT4 / genetics
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Stomach / drug effects

Substances

  • ANO1 protein, mouse
  • Anoctamin-1
  • Drugs, Chinese Herbal
  • Ryanodine Receptor Calcium Release Channel
  • hange-shashinto
  • Receptors, Serotonin, 5-HT4
  • Loperamide
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse
  • Myosin-Light-Chain Kinase