title: Dual Inhibition of Ca(+2) Influx and Phosphodiesterase Enzyme Provides Scientific Base for the Medicinal Use of Chrozophora prostrata Dalz. in Respiratory Disorders.
abstract: The crude ethanolic extract of Chrozophora prostrata (Cp.Cr) was tested using in vivo and ex vivo assays for its possible bronchodilatory effects in order to validate its medicinal use in respiratory disorders, like asthma and cough. Cp.Cr exhibited dose-dependent inhibition of carbachol (CCh)-induced bronchospasm in anesthetized rats, similar to aminophylline. When tested on guinea-pig tracheal preparations, Cp.Cr caused relaxation of both CCh (1 μM) and high K(+) (80 mM)-induced contractions with comparable potencies, similar to papaverine, a dual inhibitor of phosphodiesterse (PDE) and Ca(+2) influx. Pre-treatment of the tracheal tissues with Cp.Cr resulted in potentiation of the inhibitory effect of isoprenaline on CCh-induced contractions, like that caused by papaverine indicative of PDE inhibitory activity, which was confirmed when Cp.Cr concentration dependently (1 and 3 mg/mL) increased intracellular cAMP levels of the tracheal preparations, like papaverine. Cp.Cr shifted concentrationresponse curves of Ca(+2) constructed in guinea-pig tracheal preparation towards right with suppression of the maximum response, similar to both verapamil and papaverine. These data indicate bronchodilator activity of Chrozophora prostrata mediated possibly through dual inhibition of PDE and Ca(+2) influx, thus, showing therapeutic potential in asthma with effect enhancing and side-effect neutralizing potential Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, 74800, Karachi, Pakistan.|Faculty of Pharmacy, Government College University, Faisalabad, 38000, Pakistan.
authors.forename: Usman
authors.initials: U
authors.lastname: Arshad
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, 74800, Karachi, Pakistan.|College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, 11481, Saudi Arabia.
authors.forename: Samra
authors.initials: S
authors.lastname: Bashir
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, 74800, Karachi, Pakistan.|Department of Pharmacy, College of Health Sciences, Mekelle University, PO Box 1871, Mekelle, Ethiopia.
authors.forename: Najeeb
authors.initials: N
authors.lastname: -Ur-Rehman
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, 74800, Karachi, Pakistan.
authors.forename: Tahir
authors.initials: T
authors.lastname: Yaqub
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, 74800, Karachi, Pakistan.|Pakistan Council for Science and Technology, Shahra-e-Jamhuriat, G-5/2, Islamabad, Pakistan.
authors.forename: Anwarul-Hassan
authors.initials: AH
authors.lastname: Gilani
mesh_terms: D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006168:Guinea Pigs; D029001:Herbal Medicine / Q000379:methods*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology / Q000627:therapeutic use*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012131:Respiratory Insufficiency / Q000188:drug therapy*
chemical_list: D001993:Bronchodilator Agents; D010276:Parasympatholytics; D010936:Plant Extracts; D010727:Phosphoric Diester Hydrolases
keywords: Chrozophora prostrata; bronchodilator; calcium antagonist; phosphodiesterase inhibitory