Multiple Pathway–Mediated Gut-Modulatory Effects of Maerua subcordata (Gilg) DeWolf

Abstract

Background

Gastrointestinal disorders are often poorly managed, especially in developing countries, where there are limited resources and therapeutic options. Despite the rich diversity of medicinal plants that offer effective treatment options with fewer side effects, studies that provide scientific verification are lacking. Maerua subcordata (Gilg) DeWolf is among the plants claimed to have wide traditional medicine, use, including as a remedy against gastrointestinal problems. Therefore, this work aimed to evaluate the gut-modulatory effects of a crude leaf extract of M. subcordata (MSL.Cr), as well as its possible mechanism of action.

Methods

A castor oil (10 mL/kg)–induced diarrheal mouse model was used to evaluate the antidiarrheal effect of MSL.Cr, and the spasmodic/antispasmodic effect of the extract was assessed using isolated rabbit jejunum with and without addition of standard cholinergic agonists/antagonists to predict the possible mechanism of action.

Results

MSL.Cr exhibited 40% and 80% protection against castor oil–induced diarrhea in mice at doses of 500 and 1,000 mg/kg, respectively. In isolated rabbit jejunum, the extract increased spontaneous contractions at low doses (0.01–0.1 mg/mL), and was sensitive to atropine, whereas it showed complete inhibition at higher doses (0.3–1 mg/mL). It was shown that the relaxant effect was possibly mediated by the involvement of phosphodiesterase-enzyme inhibition and K⁺-channel activation. The extract potentiated the control concentration–response curve of carbachol, shifting it to the left, similarly to the control drug papaverine. The potassium-channel opening–like activity of MSL.Cr was possibly mediated by the involvement of aspecific K⁺-channels inhibition, since tetraethylammonium, anunselective antagonist of K⁺ channels, significantly reversed its inhibitory effect.

Conclusion

This study showed that the M. subcordata leaf extract demonstrated gut-modulatory effects, possibly mediated by a combination of muscarinic-receptor stimulation, phosphodiesterase inhibition, and aspecific K⁺-channel activation.

Keywords:

• Maeruaa subcordata
• constipation
• diarrhea
• phosphodiesterase inhibition
• K⁺ channel activation

Abbreviations

ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; CCB, Ca²⁺-channel blocker; CCh, carbachol; CRCs, concentration–response curves; Gb, glibenclamide; TEA, tetraethylammonium; GI, gastrointestinal; MSL.Cr, crude extract of M. subcordata leaf; PDE, phosphodiesterase; TMA, tetramethylammonium.

Data-Sharing Statement

All data sets used and analyzed during this study will be available from the corresponding author on reasonable request.

Ethical Approval

The study was approved by the ethical review committee of Barrett Hodgson University (BR-ER/Pharmacy-001/2020/PI-Dr Amber Hanif Palla).

Acknowledgments

The authors are thankful to Barrett Hodgson University, Karachi, Pakistan and Mekelle University, Mekelle, Ethiopia for providing necessary facilities to carry out this research.

Author Contributions

MGH and GGS collected the plant material, prepared the extract, and did the acute-toxicity studies. AK helped in the extraction and transporting of samples from Ethiopia to Pakistan. AHP and NUR did the antidiarrheal tests and related experiments, data analysis, and description. All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors do not have any conflicts of interest to disclose.