Evaluation of bronchodialatory and antimicrobial activities of Otostegia fruticosa: A multi-mechanistic approach

Mohd Nazam Ansari; Najeeb Ur Rehman; Aman Karim; Tiegsti Bahta; Khalil Y Abujheisha; Syed Rizwan Ahamad; Faisal Imam

doi:10.1016/j.jsps.2020.01.007

Evaluation of bronchodialatory and antimicrobial activities of Otostegia fruticosa: A multi-mechanistic approach

Saudi Pharm J. 2020 Mar;28(3):281-289. doi: 10.1016/j.jsps.2020.01.007. Epub 2020 Jan 31.

Authors

Mohd Nazam Ansari¹, Najeeb Ur Rehman¹, Aman Karim², Tiegsti Bahta³, Khalil Y Abujheisha⁴, Syed Rizwan Ahamad⁵, Faisal Imam⁶

Affiliations

¹ Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
² Department of Pharmacognosy, School of Pharmacy, College of Health Sciences, P.O Box 1871, Mekelle University, Mekelle, Ethiopia.
³ Department of Pharmacy, College of Health Sciences, P.O Box 298, Aksum University, Aksum, Ethiopia.
⁴ Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
⁵ Central Laboratory, Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁶ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Abstract

Otostegia fruticosa, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, O. fruticosa has been used for the treatment of several respiratory-related disorders. The present study was designed to evaluate the bronchodilatory and antimicrobial activities of O. fruticosa leaves crude extract (Of.Cr). Ex-vivo experiments were conducted on guinea-pig trachea provided with physiological oxygenated buffer solution using emkaBath setup. The crude extract was analyzed by gas chromatography-mass spectrometry. Of.Cr, showed the presence of terpenes, fragrance components, saponins, and higher fatty acids. Of.Cr when tested on contracted tracheal chains with carbamylcholine (CCh, 1 µM) and high K⁺ (80 mM) produced relaxation by showing higher potency against CCh with incomplete inhibition of high K⁺. Dicyclomine, used as a positive control, also showed selectively higher potency to inhibit CCh when compared with its effect against K⁺. In the anticholinergic curves, Of.Cr at 1 mg/mL deflected CCh-induced concentration-response curves (CRCs) competitively to the right like dicyclomine (0.03 µM) and atropine whereas a higher dose of Of.Cr (3 mg/mL) produced a non-parallel shift in the CCh curves like a higher dose of dicyclomine (0.1 µM). In the calcium channel inhibitory assay, Of.Cr at 3 & 5 mg/mL, deflected CRCs of Ca⁺⁺ to the right like verapamil, used as positive control. Of.Cr, at concentrations (1-3 mg/mL) increases cAMP levels in isolated tracheal homogenates, similar to positive control phosphodiesterase inhibitor (papaverine). When tested for antibacterial activity against standard and clinical strains, Of.Cr was found more active (MIC 475 µg/ml) against S. aureus (NCTC 6571), while the maximum inhibition (MIC 625 µg/ml) was observed by the extract when tested against MRSA. These results determine the mechanistic pathways of the observed bronchodilatory effect of Otostegia fruticosa with a combination of anticholinergic and dual inhibition of phosphodiesterase and voltage-gated Ca⁺⁺ channels.

Keywords: Antimicrobial; Antimuscarinic; Asthma; Bronchodilatation; Ca++ channel blocker; Otostegia fruticosa; Phosphodiesterase inhibitor.