Solvent Fractions of Daniellia oliveri ((Rolfe) Stem Bark Modulate Rat Liver Mitochondrial Permeability Transition Pore


  • Olufunso Olabode Olorunsogo Laboratories for Biomembrane Research and Biotechnology, Biochemistry Department


Mitochondrial-dependent cell death is initiated by the release of cytochrome c due to the opening of the mitochondrial permeability transition (mPT) pore, a pharmacological target for drug development in the treatment of diseases associated with dysregulated apoptosis. Daniellia oliveri (DO) is traditionally used in management of breast tumours, sickle cell anaemia and diabetes. This study evaluated the effects of solvent fractions of D. oliveri stem bark extract on the modulation of the mPT pore. The crude ethanol extract (EEDO) of the stem bark was partitioned successively with n – hexane (HFDO), chloroform (CFDO), ethyl acetate (EAFDO) and ethanol (EFDO) to obtain their respective fractions. Mitochondrial permeability transition (mPT), mitochondrial ATPase (mATPase) activity, cytochrome c release and mitochondrial lipid peroxidation were assessed spectrophotometrically. The EEDO and EFDO significantly induced (p < 0.05) mPT pore opening with induction folds of 15.4 and 12.2 folds, respectively at the highest concentration (420 µg/ml) in the absence of calcium while inductive effects of CFDO and EAFDO were not significant. The inductive effect of EFDO resulted in significant release of cytochrome c to the cytosol. In contrast, all fractions of DO had mild inhibitory effects on calcium-induced opening of the mPT pore except CFDO that displayed strong reversal of pore opening (86%) greater than spermine (73%), a standard inhibitor.  Furthermore, at pH 7.4, all solvent fractions of D. oliveri stem bark significantly (p < 0.05) inhibited Fe2+ - induced lipid peroxidation in a concentration-dependent manner and EFDO showed maximum enhancement effect of mATPase activity compared to control and other fractions. In this regard, enhancement effect of 63% was obtained at 420 µg/ml of EFDO which was comparable to 2, 4-dinitrophenol (68%), the standard uncoupler of oxidative phosphorylation These findings show clearly that Daniellia oliveri contains bioactive agents that either induce or inhibit calcium-induced opening of the mPT pore and therefore modulate mitochondrial-mediated cell death and  this justifies the use of the plant in management of diseases associated with dysregulated cell death.  Further studies on the isolation and characterization of the compounds responsible for modulating the mitochondrial permeability transition pore will therefore yield positive results in drug design in situations or diseases associated with dysregulated cell death.


Adaku VI, Okwesile CN (2008). Antihyperglycaemic Effect of aqueous extract of Daniellia oliveri and Sarcocephalus latifolius roots on key carbohydrates metabolic enzymes and glycogen in experimental diabetes. Biochemistri 20 (2), 63 – 70.

Adisa RA, Olorunsogo OO (2013). Robustaside B and para hydroxyphenol: Phenolic and antioxidant compounds purified from Cnestis ferruginea D.C induced membrane permeability transition in rat liver mitochondria. Molecular Medicine Reports 8(5), 1493-1498.

Appaix F, Minatchy MN, Riva-Lavieille C, Olivares J, Antonsson B, Saks VA (2000). Rapid spectrophotometric method for quantitation of cytochrome c release from isolated mitochondria or permeabilized cells revisited. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1457(3), 175-181.

Bassir O (1963). Handbook of Practical Biochemistry. Ibadan University Press, Ibadan, Nigeria p 31.

Bauer TM, Murphy E. Role of Mitochondrial Calcium and the Permeability Transition Pore in Regulating Cell Death. Circulation Research Vol. 126, No. 2 2020; 126:280–293

Bernardi P (2018). Why F-ATP synthase remains a strong candidate as the mitochondrial permeability transition pore. Front Physiol 9, 1543.

Bernardi P, Di Lisa F. The mitochondrial permeability transition pore: Molecular nature and role as a target in cardioprotection. Journal of Molecular and Cellular Cardiology. 2015; 78:100–106.

Bernardi P, Rasola A, Forte M, Lippe G (2015). The mitochondrial permeability transition pore: channel formation by F-ATP synthase, integration in signal transduction and role in pathophysiology. Physiol Rev 95(4), 1111–55.

Bonora M, Pinton P (2014). The mitochondrial permeability transition pore and cancer: molecular mechanisms involved in cell death. Frontiers in oncology 4, 302.

Bonora M, Bononi A, De Marchi E, Giorgi C, Lebiedzinska M, Marchi S, Pinton P (2013). Role of the c subunit of the FO ATP synthase in mitochondrial permeability transition. Cell Cycle.; 12(4), 674–683.
Bonora M, Pinton P (2014). The mitochondrial permeability transition pore and cancer: molecular mechanisms involved in cell death; Frontiers in Oncology 4 (302), 1-12.

Chinopoulos C, Adam-Vizi V (2010). Mitochondria as ATP consumers in cellular pathology Biochimica et Biophysica Acta 1802, 221–227.

Cooper JP, Youle, RJ (2012). Balancing cell growth and death. Current opinion in cell biology, 24(6), 802–803.

Crompton M (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem J 341 (pt 2), 233–249.

Dalziel JM (1937). The Useful Plants of West Africa. London WhiteFriars Press Ltd.

Elmore, (2007). Apoptosis: a review of programmed cell death. Toxicologic pathology 35(4), 495–516.

Fleury M (1997). Medicinal role of Copaiba balsam. Acta Botanica Gallica 144 (4), 473-497.

Gentry RV (1973). Radioactive halos. Annual Review of Nuclear Science 23(1), 347-362.

Gilbert M (2000). Medicinal importance of Copaiba oil. J. Pharmacol. 4, 1159-1164.

Hinsull SM, Bellamy D (1981) Tissue homeostasis and cell death. In: Bowen I.D., Lockshin R.A. (eds) Cell death in biology and pathology. Springer, Dordrecht. pp 123-144.

Jamshidi-Kia F, Lorigooini Z, Amini-Khoei H (2018). Medicinal plants: past history and future perspective. J Herbmed Pharmacol 7(1), 1-7.

Johnson D, Lardy H (1967). Isolation of liver or kidney mitochondria. Methods Enzymol 10, 94-6.

Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, Piacentini M. (2005). Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell death and differentiation 12(12), 1463-1467.

Lapidus RG, Sokolove PM (1993). Spermine inhibition of permeabilitytransition of isolated rat liver mitochondria; An investigation of mechanism. ArchBiochem Biophys 306(1), 246-253.

Lockshin RA, Zakeri Z (2007). Cell death in health and disease. Journal of cellular and molecular medicine 11(6), 1214–1224.

Mahomoodally MF (2013). Traditional medicines in Africa: an appraisal of ten potent african medicinal plants. Evidence-based complementary and alternative medicine: eCAM 617459.

Martin KR (2006) Targeting apoptosis with dietary bioactive agents. Exp Biol Med 231(2),117–29.

Millimouno FM, Dong J, Yang L, Li J, Li X (2014). Targeting apoptosis pathways in cancer and perspectives with natural compounds from mother nature. Cancer Prev Res. 7(11), 1081–107.

Najafi M, Farajnia S, Mohammadi M, Badalzadeh R, Ahmadi-Asl N, Baradaran B,et al. (2014). Inhibition of mitochondrial permeability transition pore restores the cardioprotection by postconditioning in diabetic hearts. J Diabetes MetabDisord 13, 106.

Odewusi AF, Oyeyemi MO, Olayemi FO, Emikpe B, Ehigie LO, Adisa RA, Olorunsogo OO (2010). Effects of the decoction of Momordica charantia (bitter melon) on Mitochondrial Membrane Permeability Transition Pore (MMPTP) and fertility in normal male albino rats. African Journal of Medicine & Medical Sciences 39, 45−57.

Olorunsogo OO, Bababunmi EA Bassir O (1979). Uncoupling effect of Nphosphonomethylglycine on at liver mitochondria. Biochem. Pharm. 27, 925- 927.

Olorunsogo OO, Malomo SO (1985). Sensitivity of Oligomycininhibitedrespiration of isolated rat liver mitochondriato perfluidone, a fluorinated arylalkylsulfonamide. Toxicology 35 (3), 231-40.

Osellame LD, Blacker TS, Duchen MR (2012). Cellular and molecular mechanisms of mitochondrial function. Best practice & research. Clinical endocrinology & metabolism 26(6), 711–723.
Oyebode OT, Akinyelu OA, Oamen EA, Olorunsogo OO (2018). Methanol fraction of Calliandra portoricensis root bark activates caspases via alteration in mitochondrial viability in vivo. J Herbmed Pharmacol 7(4), 251-258.

Policy and Operational Guidelines for Botanical Gardens of NCAC (1992) Printed by Danjuma Adamu, Bukos, Jos, Nigeria.

Raffauf MD (1992). Raffauf. Medicinal potentials of oleoresin. N. Engl. J. Med. 4, 214-301.

Rasola A, Bernardi P (2011). Mitochondrial permeability transition in Ca (2+)-dependent apoptosis and necrosis. Cell Calcium 50, 222–233.

Ruberto G, Baratta M, Deans S, Dorman H. (2000). Antioxidant and antimicrobial activity of Foeniculum vulgare and Crithmum maritimum essential oils. Planta Med 66, 687 -693.

Seidlmayer LK, Gomez-Garcia MR, Blatter LA, Pavlov E, Dedkova EN (2012). Inorganic polyphosphate is a potent activator of the mitochondrial permeability transition pore in cardiac myocytes. J Gen Physiol 139(5), 321–31.

Šileikytė J, Forte M (2019). The Mitochondrial Permeability Transition in Mitochondrial Disorders. Oxidative medicine and cellular longevity 3403075.

Suh DH, Kim MK, Kim HS, Chung HH, Song YS. (2013). Mitochondrial permeability transition pore as a selective target for anti-cancer therapy. Frontiers in oncology 3, 41.
Survey Report (1998). Anti-tumor plant. Practice of Traditional Medicine in N/E Sub-region of Nigeria. Conducted by ATBU, Bauchi in collaboration with NIPRD, Abuja.

Webster KA (2012). Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species. Future cardiology 8(6), 863–884.

Zamzami N, Larochette, N, Kroemer, Guido (2005). Mitochondrial permeability transition in apoptosis and necrosis. Cell death and differentiation, 12 Suppl 2. 1478-80.





Nutrition/Natural Product and Drug Development