# Investigations of the voltage-gated Ca++ channels and phosphodiesterase enzyme inhibitory-like potential explain the medicinal use of Otostegia fruticosa in diarrhea and hypermotile gut

## TL;DR

This study explores how Otostegia fruticosa extract may help treat diarrhea and gut spasms by blocking calcium channels and inhibiting enzymes.

## Contribution

The study provides the first detailed pharmacodynamic analysis of O. fruticosa's antispasmodic effects and dual enzyme inhibition.

## Key findings

- The extract significantly protected mice from castor-oil-induced diarrhea at 200 and 400 mg/kg.
- The extract inhibited intestinal contractions in a dose-dependent manner, similar to known inhibitors like papaverine.
- The extract showed bactericidal activity against enteric pathogens like E. coli and Salmonella.

## Abstract

The leaves of Otostegia fruticosa have been used in traditional medical systems to treat diarrhea and gut spasms. In this study, we evaluate the possible gut inhibitory roles of the crude extract of O. fruticosa using mice for in vivo, rabbits for ex vivo, and selected enteric pathogenic bacteria for in vitro assays.

Castor-oil-induced diarrhea was used to assess the diarrheal protection of the extract in mice, while CaCl2-induced excitatory concentration–response curves (CRCs) and isoprenaline-induced inhibitory CRCs were constructed for isolated rabbit intestines to explore Ca++ channel blockade and phosphodiesterase (PDE) inhibitory-like pathways, respectively. Moreover, the antibacterial activity of the extract was tested against selected bacteria.

The extract protected mice from castor-oil-mediated diarrhea significantly compared to the saline control group at doses of 200 and 400 mg/kg. In the isolated jejunum, the extract inhibited both spontaneous and high K+-depolarized contractions at comparable concentrations in a dose-dependent manner (0.01–1 mg/mL) similar to papaverine, which is a dual inhibitor of the PDE enzymes and L-type Ca++ channels. The indirect functionality of the papaverine-like dual inhibitory actions of the extract was confirmed when pretreatment with the crude extract displaced the Ca++ excitatory CRCs to the right with suppression of the maximum response, similar to verapamil; moreover, the PDE inhibitory effect was authenticated by a leftward shift in the isoprenaline-induced inhibitory CRCs. The extract showed bactericidal activity with a resultant minimum inhibitory concentration (MIC) of 550 μg/mL against Escherichia coli, Shigella sonnei, and Salmonella typhimurium, whereas the extended-spectrum β-lactamase-producing E. coli strain was found to be sensitive to a higher concentration of the extract (MIC of 675 μg/mL).

The present study is a pilot report on the detailed pharmacodynamics of the antispasmodic effects of the crude extract of O. fruticosa, with possible dual inhibition of the Ca++ channels and PDE-like effects, which provides a sound basis for its medicinal usage in hyperactive gut disorders. The O. fruticosa extract was further demonstrated to be effective against both enteric and non-enteric pathogens, which might support its use in the treatment of infectious diarrhea.