Evaluation of mechanism for antihypertensive action of Clerodendrum colebrookianum Walp., used by folklore healers in north-east India.
BACKGROUND
The present investigation was aimed to justify the pharmacological basis in traditional use of Clerodendrum colebrookianum as antihypertensive agent in north-east India.


METHODS
The aqueous extract (AECc), its aqueous, n-butanol (nBFCc), Ethyl-acetate (EtFCc) and Chloroform fractions of C. colebrookianum leaves were evaluated for antihypertensive potential by using fructose-induced hypertension model in rats and in isolated frog heart. The ex-vivo muscarinic action in isolated rat ileum, in-vitro assay for Rho-kinase (ROCK -II), phosphodiesterase-5 (PDE-5) and angiotension converting enzyme (ACE) were also carried out to establish the mechanism of action of samples. The total phenolic and flavonoied contents in test samples were estimated to establish phyto-pharmacological relationship.


RESULTS
The 100μg/mL test samples were showed calcium antagonism in rat ileum and at 50μg/mL and 75μg/mL doses exhibited ROCK-II and PDE-5 inhibition respectively where, EtFCc was caused maximum 68.62% (ROCK-II) and 52.28% (PDE-5) inhibition, but none of the sample was exhibit effect in ACE at 100μg/mL. The test samples also showed negative inotropic and chronotropic effect on isolated frog heart and significant (P<0.001) reduction in systolic blood pressure and heart rate in hypertensive rats compared to control. The total phenolic content maximum 80μg gallic acid equivalents in nBFCc and flavonoids content maximum 69.57μg Quercetin equivalent in AECc were estimated.


CONCLUSIONS
These observations established the traditional claim and thus C. colebrookianum could be a potent antihypertensive agent for use in future. The antihypertensive effect mediated by cholinergic action and following ROCK - II, PDE-5 inhibition of C. colebrookianum.
Pharmacology Laboratory, Medicinal Plants and Horticultural Resources Division, Institute of Bioresources and Sustainable Development (IBSD), Department of Biotechnology, Government of India, Takyelpat Institutional Area, Imphal, Manipur 795001, India. lokeshdeb.ibsd@nic.in
Deb
D
Lokesh
Dutta
D
Amitsankar
D000818:Animals; D000959:Antihypertensive Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D032409:Clerodendrum / Q000737:chemistry*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D005632:Fructose; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007194:India; D008297:Male; D008519:Medicine, Traditional; D018721:Muscarinic Agonists / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010636:Phenols / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018515:Plant Leaves; D011898:Ranidae; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D000959:Antihypertensive Agents; D005419:Flavonoids; D018721:Muscarinic Agonists; D010636:Phenols; D010936:Plant Extracts; D005632:Fructose; D054460:rho-Associated Kinases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D007703:Peptidyl-Dipeptidase A; D002118:Calcium