*Article Achillea fragrantissima* **Essential Oil: Composition and Detailed Pharmacodynamics Study of the Bronchodilator Activity**

**Najeeb Ur Rehman 1,\*, Mohammad Ayman A. Salkini 2, Hatem M. K. Alanizi 3, Abdulrahman G. Alharbi 4, Mohammed H. Alqarni <sup>2</sup> and Maged S. Abdel-Kader 2,5**


**Abstract:** The bronchodilator effect of the *Achillea fragrantissima* essential oil (AFO) was studied in guinea pigs' tracheas and the influence of drying on the quantity and composition of AFO was studied using GC-MS and GC analyses. AFO produced a complete and potent relaxation against carbachol (CCh), while lower potency and partial efficacy were observed against high K+ (80 mM), thus producing dual inhibitory effects similar to dicyclomine. The anticholinergic-like action was further confirmed when pre-incubation tracheal tissues were used at lower concentrations with AFO displacing the CCh concentration-response curves (CRCs) to the right in a competitive manner similar to atropine. However, non-parallel shifts in CCh CRCs were observed with higher doses, similar to dicyclomine. Further confirmation of the CCB-like effect was obtained from the non-specific deflection of Ca++ CRCs toward the right using the pre-incubated tissues with AFO in Ca++ free medium, similar to verapamil. When AFO was tested against low K+-mediated contractions to explore the possible involvement of additional antispasmodic mechanism(s), AFO interestingly showed a complete inhibition with a higher potency. This inhibition was found to be sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP), whereas glibenclamide (Gb) remained inactive. These results show that AFO possesses bronchodilator effects predominantly from its anticholinergic and K+ channel activation followed by weak Ca++ channels inhibition.

**Keywords:** *Achillea fragrantissima* oil; GC-MS; bronchodilator; anticholinergic; Ca++ channel blocker; potassium channel opener; guinea pig trachea
