ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Investigation of the voltage-gated Ca++ channels and phosphodiesterase enzyme inhibitory-like potential explains the medicinal use of Otostegia fruticosa in diarrhea and hypermotile gut
Provisionally accepted
Najeeb Ur Rehman1*
Dr Mohd Nazam Ansari1
Nasser Abdulaziz Alalaiwah1Eyad Omar Alotibi1
Aman Karim2Tiegist Bahta3Khalil Y Abujheisha4Muhammad Noman5- 1Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
- 2Rawalpindi Medical University, Rawalpindi, Pakistan
- 3Aksum University, Aksum, Ethiopia
- 4Palestine Polytechnic University, Hebron, Palestine, Hebron, Palestine
- 5Quaid-i-Azam University, Islamabad, Pakistan
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Abstract Background: The leaves of Otostegia fruticosa (Of.Cr) was haves been used in the traditional system to treat diarrhea and gut spasm. This study evaluated the possible gut inhibitory role of Of.Cr using mice for in-vivo, rabbits for ex-vivo, and selected enteric pathogenic bacteria for in-vitro assays. Methods: Castor oil-induced diarrhea in mice was used to test the diarrheal protection of Of.Cr while CaCl2-induced excitatory concentration response curves (CRCs) and isoprenaline-induced inhibitory CRCs in isolated rabbit intestine were used constructed to explore the Ca++ channels blockade and phosphodiesterase inhibitory-like pathways, respectively, whereas antibacterial activity was tested against selected bacteria. Results: The extract protected mice from castor oil-mediated diarrhea significantly compared to the saline control group at 200 and 400 mg/kg. In the isolated jejunum, Of.Cr inhibited both the spontaneous and/or high K+-depolarized contractions at comparable concentrations in a dose-dependent fashion (0.01 to 1 mg/mL), in a pattern similar to papaverine, a dual inhibitor of phosphodiesterase enzyme and L-type Ca++ channels. The indirect functional confirmation of the papaverine-like dual inhibitory actions of Ca++ channels and phosphodiesterase enzyme(PDE) of Of.Cr was confirmed when Of.Cr pretreatment displaced the Ca++ excitatory concentration-response curves (CRCs) to the right with suppression of the maximum response like verapamil, whereas the PDE-inhibitory effect was authenticated by a leftward shift in the isoprenaline-induced inhibitory CRCs. Of.Cr showed bactericidal activity with resultant MIC ofat 550 µg/mL as MIC against Escherichia coli (E. coli), Shigella sonnei, and Salmonella typhi, whereas the extended-spectrum β-lactamase (ESBL)-producing E. coli were found sensitive to the higher concentration of Of.Cr (MIC; 675 µg/mL). Conclusion: This is the first report with detailed pharmacodynamics of the antispasmodic effect of the O. fruticosa extract with possible involvement of the dual inhibition of Ca++ channels and PDE-inhibitory-like effects and thus provides a sound basis for its medicinal uses in hyperactivity-related gut disorders. O. fruticosa extract proved effective against both enteric and non-enteric pathogens, thus might support its use in infectious diarrhea.
Keywords: Antispasmodic, Ca++ channel blocker, Otostegia fruticosa, phosphodiesterase inhibitor, Verapamil
Received: 17 Jan 2026; Accepted: 13 Feb 2026.
Copyright: © 2026 Rehman, Ansari, Alalaiwah, Alotibi, Karim, Bahta, Abujheisha and Noman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Najeeb Ur Rehman
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