title: Pharmacological basis for the medicinal use of polyherbal formulation and its ingredients in cardiovascular disorders using rodents.
abstract: BACKGROUND
  A compound herbal formulation (POL4) has been used in the indigenous system of medicine to treat cardiometabolic disorders like diabetes and associated hypertension. POL4and most of its constituents have not been studied widely for its therapeutic use in hypertension. This study is aimed to determine the efficacy and possible insight into mechanism(s) for the medicinal use of POL4and its ingredients in hypertension.
  
  
  METHODS
  The aqueous methanolic extracts of POL4(POL4.Cr) and its components [Cichorium intybus (Ci.Cr), Gymnema sylvestre (Gs.Cr), Nigella sativa (Ns.Cr) and Trigonella foenum graecum (Tfg.Cr)] were tested for blood pressure lowering activity in anaesthetized Sprague-Dawley rats. To assess the vasomodulatory effect, isolated tissue experiments were performed on rat aortic strips using isometric force transducer coupled with PowerLab data acquisition system.
  
  
  RESULTS
  Administration of POL4to rats caused a dose-dependent (1-100 mg/kg) fall in mean arterial pressure (MAP) with maximum effect of 85.33 ± 1.76% at 100 mg/kg, similar to the effect of verapamil. All ingredients of POL4also decreased blood pressure with varying efficacy in following order Ns.Cr ≅ Ci.Cr > Tfg.Cr > Gs.Cr. In rat aortic preparations, POL4and its ingredients inhibited K+(80 mM)-induced contractions, Ci.Cr was the most potent followed by Ns.Cr > Tfg.Cr > Gs.Cr ≅ POL4. Against phenylephrine (P.E) contractions, Ci.Cr and Tfg.Cr exhibited complete relaxation, while POL4.Cr, Gs.Cr and Ns.Cr showed vasomodulatory effect. The Ca++antagonist activity was confirmed when POL4and its ingredients shifted Ca++concentrations-response curves to the right in a manner similar to that of verapamil. On baseline of rat aorta, the parent formulation and its ingredients (except Tfg.Cr) exhibited partially phentolamine (1 μM)-sensitive vasoconstriction.
  
  
  CONCLUSIONS
  These data show that POL4and its constituents possess blood pressure lowering activity mediated through inhibition of Ca++influx via membranous Ca++channels and receptor (α-adrenergic) operated pathways. Thus, this study provides a rationale to the medicinal use of POL4and its constituents in hypertension.
authors.affiliation: Natural Product Research Division, Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.|Faculty of Pharmacy, University of Sargodha, Sargodha, 40100, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Malik
authors.affiliation: Natural Product Research Division, Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan. hassan.mehmood@aku.edu.
authors.forename: Malik Hassan
authors.initials: MH
authors.lastname: Mehmood
authors.affiliation: Natural Product Research Division, Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.|The Aga Khan University Medical College, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.
authors.forename: Hajra
authors.initials: H
authors.lastname: Channa
authors.affiliation: Faculty of Pharmacy, University of Sargodha, Sargodha, 40100, Pakistan.
authors.forename: Muhammad Shoaib
authors.initials: MS
authors.lastname: Akhtar
authors.affiliation: Natural Product Research Division, Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.|Pakistan Council for Science and Technology, G-5/2, Islamabad, 44000, Pakistan.
authors.forename: Anwarul-Hassan
authors.initials: AH
authors.lastname: Gilani
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D018651:Cichorium intybus; D004195:Disease Models, Animal; D005419:Flavonoids / Q000032:analysis; D006168:Guinea Pigs; D031104:Gymnema sylvestre; D006325:Heart Atria / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D031881:Nigella sativa; D010636:Phenols / Q000032:analysis; D008517:Phytotherapy / Q000379:methods*; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D029910:Trigonella; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D005419:Flavonoids; D010636:Phenols; D028321:Plant Preparations
keywords: Antihypertensive; Ca++ antagonist; POL4; Vasomodulatory; α-adrenergic antagonist