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Background: Mitochondrial-mediated cell death begins with opening of mitochondrial membrane permeability transition (mPT) pore and medicinal plants contain phytochemicals that modulate the mPT pore.
Hypothesis and Purpose: We investigated the modulatory effects of crude methanol extract of Daniellia oliveri leaves (CMDO) on mPT pore in vitro.
Study Design and Methods: Phytochemical screening and antioxidant activities of crude methanol extract of Daniellia oliveri leaves (CMDO) were evaluated according to standard procedures. CMDO was partitioned into chloroform fraction (CFDO), ethyl acetate fraction (EFDO) and methanol fraction (MFDO) by Vacuum liquid chromatography (VLC). Effects of CMDO, CFDO, EFDO and MFDO on mPT pore were assessed by spectrophotometry. Effects of the most potent fraction on mitochondrial ATPase, Fe-induced lipid peroxidation and cytochrome c release were assessed by spectrophotometry. CMDO was subjected to GC-MS analysis to identify the bioactive compounds present.
Results: CMDO contains phytochemicals and showed appreciable total flavonoid content (0.483±0.02 QE mg/100g), total phenolic content (0.886±0.12 GAE mg/100g), total antioxidant capacity (0.039±0.001 AE mg/100 g), ferric antioxidant reducing power (IC50=350 µg/ml) and 2, 2-diphenyl-1 picrylhydrazyl (DPPH) radical scavenging activity (IC50=166 µg/ml). The maximum induction of mPT pore opening in the absence and presence of calcium, respectively, were as follows: CMDO (10.11 folds, 5.18 folds), CFDO (19.9 folds, 16.3 folds), EFDO (7.5 folds, 23.2 folds), MFDO (22.2 folds, 31.3 folds). The most potent mPT pore-opening fraction (MFDO) enhanced mitochondrial ATPase activity, inhibited Fe-induced lipid peroxidation and caused cytochrome c release. GC-MS analysis of CMDO revealed the presence of bioactive compounds including methyl propanamide, Dibutyl phthalate, saturated and unsaturated fatty acids.
Conclusion: Methanol fraction (MFDO) of CMDO most potently induced mPT pore opening via enhancement of mitochondrial ATPase activity, which was substantiated by the release of cytochrome c (in vitro). This includes MFDO as a candidate pharmacologic remedy for diseases associated with insufficient apoptosis.
Sorrentino V, Menzies KJ, Auwerx J. Repairing mitochondrial dysfunction in disease. Annu. Rev. Pharmacol. Toxicol. 2018;58:353–389.
Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305: 626-9.
Adams JM. Ways of dying: Multiple pathways to apoptosis. Genes Dev. 2003;17(20):2481-95.
Elustondo PA, Nichols M, Negoda A, Thirumaran A, Zakharian E, Robertson GS, Pavlov EV. Mitochondrial permeability transition pore induction is linked to formation of the complex of ATPase C-subunit, polyhydroxybutyrate and inorganic polyphosphate. Cell Death Discovery. 2016;2:16070.
Jennifer Q, Kwong 1. Jeffery DM. Physiological and Pathological Roles of the Mitochondrial Permeability Transition Pore in the Heart. Cell Metabolism 21, February 3, Elsevier Inc. cmet.2014.12.001; 2015.
Oyedeji TA, Akintehinse T, Avan ED, Soremekun OO, Solomon OE, Olorunsogo OO. Extracts of Adenopus breviflorus induce opening of Rat Liver Mitochondrial Membrane Permeability Transition Pore. Biokemistri. 2017;29(4):140-145.
Olanlokun OJ, Oyebode TO, Olorunsogo OO. Effects of Vacuum Liquid Chromatography (Chloroform) Fraction of the Stem Bark of Alstonia boonei on Mitochondrial Membrane Permeability Transition Pore. J Basic Clin Pharma. 2017;8:221-225.
Oyebode OT, Akinyelu OA, Oamen EA, Olorunsogo OO. Methanol fraction of Calliandra portoricensis root bark activates caspases via alteration in mitochondrial viability in vivo. J Herbmed Pharmacol. 2018;7(4):251-258.
Keay RWJ, Onochie CFA, Stanfield DP. Nigerian Trees Vol. II Department of Forest Research, Ibadan. 1964;65–66.
Djoueche CM, Azebaze AB, Dongmo AB. Investigation of Plants used for the Ethnoveterinary Control of Gastrointestinal Parasites in Bénoué Region, Cameroon, Tropicultura 29 (4), 205-211.
Ahmadu, A.A., Zezi, A.U., Yaro, A.H., 2007. Antidiarrheal activity of the leaf extracts of Daniellia oliveri Hutch and Dalz (Fabaceace) and Ficus sycomorus Miq (Moraceace), Afr J Tradit Complement Altern Med. 2011;4(4):542-528.
Musa AD, Yusuf GO, Ojogbane EB, Nwodo OFC. Screening of Eight Plants Used In Folkloric Medicine for the Treatment of Typhoid Fever, J Chem Pharm Res. 2010;2(4):7-15.
Muanda F, Koné D, Dicko A, Soulimani R, Younos C. Phytochemical composition and antioxidant capacity of three malian medicinal plant parts. Evidence-based complementary and alternative medicine: CAM, 20 674320; 2011.
Iwueke AV, Nwodo OFC. Antihyperglycaemic effect of aqueous extract of Daniellia oliveri and Sarcocephalus latifolius roots on key carbohydrate metabolic enzymes and glycogen in experimental diabetes, Biokemistri. 2008;20(2):63-70.
Kareem SH. Cytotoxic Activity of Verbenaceae (Daniellia oliveri) & Solanaceae (Capsicum frutescens) on Breast Cancer, Prostate Cancer, and Colon Cancer cells". ETD Collection for Tennessee State University. Paper AAI1492332; 2011.
Achem J, Oyebode OT, Akinwole M, Bolarin O, Malgwi JM, Olorunsogo OO. Solvent Fractions of Daniellia oliveri ((Rolfe) Stem Bark Modulate Rat Liver Mitochondrial Permeability Transition Pore. Arch. Bas. App. Med. 2020;8(2020):27–34.
Trease G, Evans W. A Textbook of Pharmacognosy, 13th ed. Bailliere Tinall Ltd, London; 1989.
Arvouet-Grand A, Vennat B, Pourrat A, Legret P. Standardisation d’un extrait de propolis et identification des principaux constituants. J. Pharma. Belg. 1994;49:462-468.
Singleton VL, Orthofer R, Lamuela-raventos RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods Enzymol. 1999;299: 152-178.
Kedare SB, Singh RP. Genesis and development of DPPH method of antioxidant assay. J. Food Sci. Technol. 2011;48:412–422.
Tundis R., Menichini, F., Bonesi, M., 2013. “Antioxidant and hypoglycaemic activities and their relationship to phytochemicals in Capsicum annuum cultivars during fruit development,” LWT—Food Science and Technology, 53 (1) 370–377.
Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E,” Analytical Biochemistry. 1999;269(2):337–341.
Johnson D, Lardy H. Isolation of liver or kidney mitochondria. Methods Enzymol. 1967;10:94-6.
Lowry OH, Rosebrough NJ. Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75.
Lapidus RG, Sokolove PM. Inhibition by spermine of the inner membrane permeability transition of isolated rat heart mitochondria. FEBS Lett. 1992;313(3):314-8.
Olorunsogo OO, Malomo SO. Sensitivity of oligomycin-inhibited respiration of isolated rat liver mitochondria to perfluidone, a fluorinated arylalkyl-sulfonamide. Toxicology. 1985;35(3):231-40.
Bassir O. Handbook of practical biochemistry. Ibadan University press, Ibadan, Nigeria. 1963;13.
Ruberto G, Baratta M, Deans S, Dorman H. Antioxidant and antimicrobial activity of Foeniculum vulgare and Crithmum maritimum essential oils. Planta. Med. 2020;66:687-693.
Appaix F, Minatchy NM, Riva-Lavieille C, Olivares AB, Saks VA. Rapid spectrophotometric method of quantification of cytochrome c release from isolated mitochondria or permeabilized cells revisited. Biochimica et Biophysica Acta (BBA)- Bioenergitcs. 2000;1457:175-181.
Zoremsiami J, Jagetia GC. The Phytochemical and thin layer chromatography profile of ethnomedcinal plant Helicia Nilagirica (Bedd). Int J Pharmacog Chinese Med. 2018;2(2):000131.
Lalrinzuali K, Vabeiryureilai M, Jagetia GC, Lalawmpuii PC. Free radical scavenging and antioxidant potential of different extracts of Oroxylum indicum in vitro. Adv. Biomed. Pharm. 2015;2(3):120–130.
Shantabi L, Jagetia GC, Ali MA, Singh TT, Devi SV. Antioxidant potential of Croton caudatus leaf extract in vitro. Transl. Med. Biotechnol. 2014;2(6):1–15.
Tejero J, Gayoso S, Caro I. Comparative analysis of the antioxidant and free-radical scavenging activities of different water-soluble extracts of green, black and oolong tea samples. Food Nutr. Sci. 2014;5(22):2157–2166.
Alavian KN, Beutner G, Lazrove E, Sacchetti S, Park HA, Licznerski P, Li H, Nabili P, Hockensmith K, Graham M. An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proc. Natl. Acad. Sci. USA. 2014;111:10580– 10585.
Rasola, A., Bernardi, P., 2011. The mitochondrial permeability transition in Ca (2+)-dependent apoptosis and necrosis. Cell. Calcium. 50, 222 -233.
Elena-Real, C.A., Díaz-Quintana, A., González-Arzola, K., Velázquez-Campoy, A., Orzáez, M, López-Rivas, .A, Gil-Caballero, D., Rosa, M.Á., Díaz-Moreno, I.,. Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition. Cell Death. 2018;9(3):365.
Xue, Z.H., Li, J.M., Cheng, A.Q., Yu, W.C., Zhang, Z.J., Kou, X.H., Zhou, .F.J. Structure identification of triterpene from the mushroom Pleurotuseryngiiwith inhibitory effects against breast cancer. Plant Foods HumNutr. 2015;70:291–296.
Surh Y. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutation Research. 1999;428:305–327.
Sakai, M., Kakutani, S., Horikawa, C., Tokuda, H., Kawashima, H., Shibata, H. Arachidonic acid and cancer risk: a systematic review of observational studies. BMC cancer. 2012;12(1):606.
Gleeson, R.P., Ayub, M., Wright, J.T., Wood, C.B., Habib, N.A., Soutter, W.P. Fatty acid control of growth of human cervical and endometrial cancer cells. British journal of cancer. 1990;61(4):500.
Carrillo, C., Cavia, M., Alonso-Torre, S.R. Antitumor effect of oleic acid; mechanisms of action. A review. Nutricion hospitalaria. 2012;27(6):1860-5.
Hayashi, Y., Fukushima, S., Hirata, T., Kishimoto, S., Katsuki, T., Nakano, M. Anticancer Activity of Free γ-Linolenic Acid on AH-109A Rat Hepatoma Cells and the Effect of Serum Albumin on Anticancer Activity of γ-Linolenic Acid in Vitro. Journal of pharmacobio-dynamics. 1990;13(11):705-711.
Harada ., Yamashita, U., Kurihara, H., Fukushi, E., Kawabata, J., Kamei, Y. Antitumor activity of palmitic acid found as a selective cytotoxic substance in a marine red alga. Anticancer research. 2002;22(5):2587-2590.
Hsieh, T.H., Tsai, C.F, Hsu, C.Y. Phthalates induce proliferation and invasiveness of estrogen receptor-negative breast cancer through the AhR/HDAC6/c-Myc signaling pathway. FASEB J, 2012;26:778–87.
Wójtowicz, A.K., Szychowski, K.A., Wnuk, A., Kajta, M. Dibutyl Phthalate (DBP)-induced apoptosis and neurotoxicityare mediated via the Aryl Hydrocarbon Receptor (AhR) but not by Estrogen Receptor Alpha (ERα), Estrogen Receptor Beta (ERβ), or Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Mouse C. Neurotox Res. 2017;31:77–89.