title: Acute toxicity and antispasmodic activities of Achillea wilhelmsii C. Koch.
abstract: Since Achillea wilhelmsii is used as antispasmodic in traditional medicine, we conducted our current work to investigate its rationale on scientific grounds. Acute toxicity studies of crude methanol extract of Achillea wilhelmsii (Aw. CMeOH) is also performed. Effect of Aw. CMeOH and its fractions were tested on isolated sections of rabbits' jejunum at test concentrations 0.01, 0.03, 1.0, 3.0, 5.0 and 10mg/ml. The test extracts, in similar concentrations, were also tested on KCl-induced contractions. Calcium chloride curves were constructed for those fractions which relaxed KCl induced contractions in the absence and presence of the test samples to investigate its possible mode of action through calcium channels. Aw. CMeOH tested positive for flavonoids, saponins, tannins, glycosides, terpenoids, sterols, phenols, carbohydrates and proteins. LD(50) for acute toxicity studies is 2707±12.6 mg/kg. Mean EC(50) values for Aw. CMeOH on spontaneous and KCl-induced contractions are 3.41±0.18 (2.56-3.8, n=6) and 0.68±0.05 (0.6-0.85, n=6) mg/ml, respectively. Respective EC(50) values for n-hexane fraction on spontaneous and KCl-induced contractions are 3.06±0.08 (2.8-3.3, n=6) and 1.68±0.8 (1.4-1.9, n=6) mg/ml, respectively. Corresponding EC(50) (mg/ml) values for chloroformic, ethylacetate and aqueous fractions of Achillea wilhelmsii on spontaneous rabbits' jejunum preparations are 4.8±0.2 (4.41-5.63, n=6), 5.07±0.15 (4.7-5.58, n=6) and 5.2±0.13 (4.91-5.64, n=4), respectively. Constructing calcium chloride curves, in the presence of 0.1 mg/ml of Aw. CMeOH, mean EC(50) value (log molar [Ca(++)]) is-1.98±0.03 (-1.89-2.05, n=6) vs. control EC(50) (log molar [Ca(++)])-2.41±0.02 (-2.32-2.44, n=6). Mean EC(50) value (log molar [Ca(++)]) for 0.3 mg/ml n-hexane fraction is-1.76±0.05 (-1.70 -1.93, n=6) vs. control EC(50) (log molar [Ca(++)]) value-2.18±0.07 (-2.0-2.46, n=6). While in the presence of chloroformic fraction (3 mg/ml), mean EC(50) (log molar [Ca(++)]) value is -2.4±0.1 (-2.78 -2.9, n=6) vs. control EC(50) (log molar [Ca(++)]) value-2.70±0.05 (-2.5-2.8, n=6). Mean EC(50) value (log molar [Ca(++)]) for ethyl acetate fraction (1 mg/ml) is-1.94±0.07 (-1.75-2.05, n=6) vs. control EC(50) (log molar [Ca(++)]) value-2.69±0.04 (-2.57-2.79, n=6). Mean EC(50) (log molar [Ca(++)]) value for residual aqueous fraction (3 mg/ml) is-1.8±0.3 (-1.71-1.84, n=6) vs. control EC(50) (log molar [Ca(++)]) -2.6±0.04 (-2.59-2.76, n=6). Whereas, the verapamil (0.1µM) EC(50) value (log molar [Ca(++)]) is-1.7±0.1 (-1.6-1.8, n=6) vs. control EC(50) value (log molar [Ca(++)])- 2.4±0.09 (-2.3-2.47, n=6). The present research work confirms that the intestinal relaxation effect of Achillea wilhelmsii is supporting its traditional use as antispasmodic. The plant species can be a source for calcium antagonist(s), which can preferably be isolated from n-hexane fraction.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, KP, Pakistan.
authors.forename: Niaz
authors.initials: N
authors.lastname: Ali
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir, KP, Pakistan.
authors.forename: Syed Wadood Ali
authors.initials: SW
authors.lastname: Shah
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir, KP, Pakistan / Department of Pharmacy, Kohat University of Science and Technology, Kohat, KP, Pakistan.
authors.forename: Ghayour
authors.initials: G
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir, KP, Pakistan.
authors.forename: Ismail
authors.initials: I
authors.lastname: Shah
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir, KP, Pakistan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shoaib
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir, KP, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Junaid
authors.affiliation: Department of Pharmacy, Abasyn University, Peshawar, KP, Pakistan.
authors.forename: Waqar
authors.initials: W
authors.lastname: Ali
mesh_terms: D031162:Achillea / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007583:Jejunum / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D011189:Potassium Chloride; D011817:Rabbits
chemical_list: D010276:Parasympatholytics; D010936:Plant Extracts; D011189:Potassium Chloride; D002122:Calcium Chloride