title: Effects of methanolic and chloroform extracts of leaves of Alstonei boonei on rat liver mitochondrial membrane permeability transition pore.
abstract: The effects of methanolic and chloroform extracts of the leaves of Alstonei boonei, a medicinal plant with anti-malarial, anti-inflammatory and analgesic properties, were assessed on liver mitochondrial membrane permeability transition (MMPT) pore were assessed in experimental animals in vitro and in vivo. The results obtained showed that calcium ions induced the opening of MMPT pore significantly (P< 0.05) in rat liver mitochondria, while spermine (0.1mM) inhibited calcium-induced opening of MMPT pore of these mitochondria thus, indicating that the mitochondria were intact, ab initio. The results further revealed the inhibitory effects of different concentrations of the various extracts of leaves of Alstonei boonei (200 microg/ml, 600 microg/ml, 1000 microg/ml, 1400 microg/ml) compared with spermine. Specifically, the data revealed that methanolic and chloroform extracts of leaves of Alstonei boonei reversed calcium-induced opening of MMPT pore in a concentration-dependent manner (26.5%, 27.4%, 56.4%, 69.3%) for methanolic extract of Alstonei boonei and (9.6%, 34.9%, 51.5% and 82.1%) for chloroform extract of Alstonei boonei, respectively. Although, the MMPT pore was not affected by low concentrations of the methanolic extract of Alstonei boonei (200 microg/ml and 600 microg/ml) in the absence of calcium, the extract at higher concentrations (1000 microg/ ml and 1400 microg/ml) induced the opening of the pore in a concentration-dependent manner. Mitochondria isolated from Wistar strain albino rats orally exposed to various doses of the methanolic extract of Alstonei boonei exhibited pore opening in the absence of calcium. In this respect, maximum (112%) induction of pore opening was obtained at 250mg/kg body weight, while minimum (31%) induction of pore opening was obtained at 200mg/kg body weight. Calcium further increased the extent of opening of the MMPT pore in animals previously exposed to methanolic extract of Alstonei boonei. These findings suggest that certain bioactive components of Alstonei boonei may be involved in inhibiting the opening of the MMPT pore in-vitro and in the induction of the opening of the pore at high doses of the extract with the eventual release of cytochrome C which is a prelude to the progression of programmed cell death.
authors.affiliation: Laboratories for Bio-membrane Research and Biotechnology, Biochemistry Department, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: T A
authors.initials: TA
authors.lastname: Salako
authors.forename: R A
authors.initials: RA
authors.lastname: Adisa
authors.forename: O O
authors.initials: OO
authors.lastname: Alao
authors.forename: O O
authors.initials: OO
authors.lastname: Adeniran
authors.forename: F O
authors.initials: FO
authors.lastname: Atanu
authors.forename: O O
authors.initials: OO
authors.lastname: Olorunsogo
mesh_terms: D000818:Animals; D029062:Apocynaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D002725:Chloroform; D004305:Dose-Response Relationship, Drug; D008297:Male; D000432:Methanol; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D018515:Plant Leaves; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000494:pharmacology* / Q000502:physiology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013096:Spermine; D002725:Chloroform; D002118:Calcium; D000432:Methanol