Mechanisms of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum diels (combretaceae): Involvement of opioidergic and (α1 and β)-adrenergic pathways

J Ethnopharmacol. 2021 Apr 6:269:113750. doi: 10.1016/j.jep.2020.113750. Epub 2020 Dec 24.

Abstract

Ethnopharmacological relevance: The plant Combretum hypopilinum Diels (Combretaceae) is used in traditional medicine for the treatment of diarrhoea and other diseases in Africa. Previously, the antidiarrhoeal activity of its methanol leaf extract was reported. However, the mechanism(s) responsible for this activity is yet to be evaluated.

Aim of the study: This study aimed to elucidate the possible mechanism(s) of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum (MECH) in mice.

Materials and methods: Phytochemical screening and acute toxicity study were conducted according to standard methods. Adult mice were orally (p.o) administered distilled water (10 ml/kg), MECH (1000 mg/kg) and loperamide (5 mg/kg). The probable mechanisms of antidiarrhoeal activity of MECH were investigated following pretreatment with naloxone (2 mg/kg, subcutaneously), prazosin (1 mg/kg, s.c), yohimbine (2 mg/kg, intraperitoneally), propranolol (1 mg/kg, i.p), pilocarpine (1 mg/kg, s.c) and isosorbide dinitrate (150 mg/kg, p.o) 30 min before administration of MECH (1000 mg/kg). The mice were then subjected to castor oil-induced intestinal motility test.

Results: The oral median lethal dose (LD50) of MECH was found to be higher than 5000 mg/kg. There were significant (p < 0.05) decrease in the charcoal movement in the mice treated with the MECH (1000 mg/kg) and loperamide (5 mg/kg). The pretreatment of the mice with naloxone, prazosin and propranolol each significantly (p<0.05) reversed the antidiarrhoeal activity produced by MECH.

Conclusion: The results obtained in this study suggest the probable involvement of opioidergic and (α1 and β)-adrenergic systems in the antidiarrhoeal activity of the methanol leaf extract of Combretum hypopilinum.

Keywords: Adrenergic pathway; Antidiarrhoeal activity; Antidiarrhoeal mechanisms; Combretum hypopilinum; Opioidergic pathway.

MeSH terms

  • Animals
  • Antidiarrheals / pharmacology*
  • Antidiarrheals / therapeutic use
  • Castor Oil / toxicity
  • Combretum / chemistry*
  • Diarrhea / chemically induced
  • Diarrhea / drug therapy*
  • Female
  • Gastrointestinal Motility / drug effects
  • Lethal Dose 50
  • Loperamide / pharmacology
  • Loperamide / therapeutic use
  • Male
  • Medicine, African Traditional
  • Methanol / chemistry
  • Mice
  • Nitric Oxide / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Plant Leaves / chemistry
  • Receptors, Adrenergic / drug effects*
  • Receptors, Cholinergic / drug effects
  • Receptors, Opioid / drug effects*
  • Signal Transduction / drug effects

Substances

  • Antidiarrheals
  • Plant Extracts
  • Receptors, Adrenergic
  • Receptors, Cholinergic
  • Receptors, Opioid
  • Nitric Oxide
  • Loperamide
  • Castor Oil
  • Methanol