Abstract
Background: The mitochondrial membrane permeability transition (MMPT) pore opening has been implicated as a final cell death pathway in numerous diseases and therefore understanding conditions dictating this opening is crucial for developing targeted therapies. Cells committed to suicide, signal the release of cytochrome c from the inner mitochondrial membrane; a point of no return in the intrinsic/mitochondrial apoptotic pathway. The efficacy of Momordica charantia (MC) against certain cancers has been linked to its ability to induce apoptosis; however, the underlying mechanism of the induction is still unknown. This study was designed to evaluate the effect of leaf extract of MC on the opening of MMPT pore in normal Wistar rat liver mitochondria.
Methodology: The leaves of MC were obtain from the Botanical Garden, OAU, Ile-Ife Campus and was cold-extracted in distilled water to obtain the Crude Water-Soluble Extract (CWSE). N-hexane,
dichloromethane, ethylacetate, butanol and aqueous fractions were obtained from the CWSE via solvent partitioning. The in vitro effects of these fractions on rat liver MMPT pore and ATPase activity at various concentrations (75, 100 and 125 µg/ml) were spectrophotometrically assayed.
Result: At all concentrations, all fractions of CWSE of MC show significant induction of the MMPT pore but the highest induction was observed at 125µg/ml of butanol fraction with a 23.56-fold increase when compared with the control group. In the same vein, the ATPase activities were also significantly enhanced by in vitro treatment with all but the ehtylacetate fraction; peaking at 14.13 mMPi/mg protein/min for the butanol fraction at 125µg/ml in comparison with the control group.
Conclusion: We thus conclude that the fractions of interest derived from the CWSE of MC are both potent inducers of and enhancers of the MMPT pore and mitochondrial ATPase activity respectively, the butanol fraction being the most potent.
Keywords: Momordica charantia, Crude water soluble extract, ATP, Mitochondrial membrane permeability transition pore, Mitochondrial ATPase activity, Mitochondrial swelling.
Résumé - 4010
Contexte: L’ouverture des pores de la transition de perméabilité membranaire mitochondriale (MMPT) a été impliquée en tant que voie de mort cellulaire finale dans de nombreuses maladies. Par conséquent, la compréhension des conditions dictant cette ouverture est cruciale pour le développement de thérapies ciblées. Les cellules suicidaires signalent la libération du cytochrome c de la membrane mitochondriale interne; un point de non-retour dans la voie apoptotique intrinsèque / mitochondriale. L’efficacité de Momordica charantia (MC) contre certains cancers a été liée à sa capacité à induire l’apoptose; néanmoins, le mécanisme sous-jacent de l’induction est encore inconnu. Cette étude visait à évaluer l’effet de l’extrait de feuille de MC sur l’ouverture des pores de MMPT dans les mitochondries de foie de rat Witsar normal.
Méthodologie: Les feuilles de MC ont été obtenues du jardin botanique, UOA, du campus Ile-Ife et ont été extraites à froid dans de l’eau distillée pour obtenir l’extrait brut soluble dans l’eau (CWSE). Le Nhexane, le dichlorométhane, l’acétate d’éthyle, le butanol et des fractions aqueuses ont été obtenus à partir de CWSE via un partage par solvant. Les effets in vitro de ces fractions sur l’activité des pores et de l’ATPase de la MMPT dans le foie de rat à diverses concentrations (75, 100 et 125 µg / ml) ont été analysés par spectrophotométrie.
Résultat: A toutes les concentrations, toutes les fractions de CWSE de MC présentent une induction significative du pore de MMPT, mais l’induction la plus élevée a été observée à 125 µg / ml de fraction de butanol avec une augmentation de 23,56 fois par rapport au groupe témoin. Dans la même veine, les activités ATPase ont également été significativement augmentées par un traitement in vitro avec toutes les fractions sauf la fraction acétate d’éthyle; culminant à 14,13 mMPi / mg de protéine / minute pour la fraction butanol à 125 µg / ml par rapport au groupe témoin.
Conclusion: Nous concluons donc que les fractions d’intérêt dérivées de la CWSE de MC sont à la fois des inducteurs puissants et des amplificateurs de l’activité du pore de MMPT et de l’ATPase
mitochondriale, la fraction butanol étant la plus puissante.
Mots-clés: Momordica charantia, extrait brut soluble dans l’eau, ATP, pore de transition de la perméabilité de la membrane mitochondriale, activité ATPase mitochondriale, gonflement mitochondrial.
Correspondence: Dr. L.O. Ehigie, Department of Biochemistry, Ladoke Akintola University of Technology,
Ogbomoso, Oyo State, Nigeria. Email:
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