Abstract
Background: Mitochondrial membrane permeability transition (MMPT) pore has emerged as a promising target for various pharmacological interventions because of the consequent release of cytochrome c upon the opening of the pore which is the point of no return for apoptosis, a form of programed cell death that is down regulated in cancer cells.
Aim: To evaluate the modulatory effects of fractions (Chloroform fraction of calliandra portoricensis( CFCP), Aqueous fraction of calliandra portoricensis (AFCP), and Ethylacetate fraction of Calliandra portoricensis (EFCP) of methanol extracts of the root bark of Calliandra portoricensis (MECP), a medicinal plant used in the traditional treatment of prostate tumour, on mitochondrial membrane permeability transition (MMPT) pore.
Methodology: Opening of the pore was assessed as mitochondrial swelling and was monitored spectrophotometrically as changes in absorbance at 540nm.
Results: Varying concentrations of MECP (10µg/ml, 20µg/ml, 40µg/ml, and 60µg/ml) induced opening of the pore,in the absence of calcium, by 1.1, 2.8, 4.5, 13.8 folds, respectively while spermine reversed this inductive effect. Interestingly, unlike MECP, EFCP and AFCP did not have any effect at lower concentrations (<40µg/ml) but induced pore opening at 60µg/ml, 80µg/ml, 100µg/ml and 120µg/ml by 1.6, 3.1, 12.7, 16.7folds, respectively for EFCP and 1.4, 5.4, 7 and 10 folds respectively, for AFCP. In the presence of calcium, the pore was slightly further opened by MECP, EFCP and AFCP. The CFCP however did not have any significant effect on the pore either in the presence or absence of calcium.
Conclusion: These findings suggest that the bioactive agents that induced the opening of the pore are present in the most potent ethylacetate fraction of the root bark of C. portoricensis. This fraction will therefore be useful for the structural elucidation of the bioactive principle in the plant and for further studies in diseases that require increased apoptosis such as cancer.
Keywords: Apoptosis, Calliandra portoricensis, mitochondrial membrane permeability transition (MMPT),cancer.
Résumé
Contexte: Le pore de transition de la perméabilité de la membrane mitochondriale(TPMM) est apparue comme une cible prometteuse pour diverses interventions pharmacologiques en raison de la libération consécutive de cytochrome c à l’ouverture du pore qui est le point de non-retour pour l’apoptose, une forme de mort cellulaire programmée, régulée vers le bas dans les cellules cancéreuses.
Objectif: évaluer les effets modulateurs des fractions (CFCP, PCAA, et EFCP) des extraits de méthanol de l’écorce de la racine de Calliandra portoricensis (MECP), qui est une plante médicinale utilisée pour le traitement traditionnel de la tumeur de prostate, sur le pore de transition de perméabilité de la membrane mitochondriale (TPMM) .
Méthodologie: L’ouverture du pore a été évaluée comme un gonflement mitochondrial et a été suivie avec des spectrophotométries tout au long des changements en absorbance à 540 nm.
Résultats: Des concentrations variables de MECP (10ìg/ml, 20ìg/ml, 40ìg/ml et 60ìg/ml) ont entraîné l’ouverture du pore, en l’absence de calcium, à 1,1, 2,8, 4,5, 13,8 plis, respectivement, tandis que la spermine a inversé cet effet inductif. Fait intéressant, contrairement au MECP, l’ EFCP et l’PCAA n’a pas eu d’effet à des concentrations plus faibles (<40ìg/ml), mais entraine l’ouverture du pore à 60ìg/ml, 80ìg/ml, 100ìg/ml et 120ìg/ml de 1,6, 3,1, 12,7, 16,7 plis, respectivement pour l’EFCP et 1,4, 5,4, 7 et 10 plis, respectivement, pour les PCAA. En présence de calcium, le pore a été un peu plus ouvert par le MECP, l’EFCP et le PCAA. L’EFCP n’a toutefois pas eu d’effet significatif sur le pore soit en présence ou en absence du calcium.
Conclusion: Ces résultats montrent que les agents bioactifs qui ont induit l’ouverture du pore sont présents dans la fraction acétate d’éthyle le plus puissant de l’écorce de la racine de portoricensis C. Cette fraction sera donc utile pour l’élucidation structurelle du principe bioactif dans la plante et pour poursuivre des études sur les maladies qui nécessitent une apoptose accrue comme le cancer.
Correspondence: OO Olorunsogo, Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria. E-mail: funsoolorunsogo@yahoo.com, oo.olorunsogo@mail.ui.edu.ng
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