Macleaya cordata protopine total alkaloids as potential treatment for diarrhoea: Mechanistic insights and target identification

Diarrhoea remains a major public health concern, particularly affecting young children and livestock. Macleaya cordata protopine total alkaloids (MPTA), a standardized extract approved in China for poultry diarrhoea, has demonstrated anti-inflammatory properties in intestinal disorders. The study aims to investigate the antidiarrheal mechanism of MPTA using castor oil- and E. coli -induced diarrhoea models in mice. We first tested MPTA for acute oral toxicity. Subsequently, the effect of MPTA on castor oil- and E. coli -induced diarrhoea in mice based on LD 50 results. Network pharmacology analysis and target competition assays (inhibitors and antagonists) were integrated to identify targets for MPTA's antidiarrheal effects. Molecular docking was used to verify the binding ability of MPTA components to these receptors. The LD 50 of MPTA was determined to be 426.1 mg/kg. The optimal MPTA activity was found at 8 mg/kg in both castor oil and in infectious models. Network pharmacology analysis revealed potential targets and pathways of MPTA against intestinal motility. The impact of MPTA on cholinergic, serotonin, dopaminergic, and adrenergic receptors was assessed using standard inhibitors and agonists to induce intestinal smooth muscle contractions or relaxations. Molecular docking confirmed the binding ability of MPTA components to these receptors. In conclusion, MPTA exhibits significant antidiarrheal effects in both castor oil and E. coli -induced diarrhoea models. Its mechanism may involve modulation of cholinergic, serotonin, dopaminergic, and adrenergic receptors, as well as inhibition of ion channels and anti-inflammatory actions. These findings highlight the potential of MPTA as a novel therapeutic agent for diarrhoea.