Effect of Different Solvent Fractions of Sarcocephalus latifolius (Smith) Bruce on Rat Liver Mitochondrial Membrane Permeability Transition (mPT) Pore
Article Sidebar
Main Article Content
Abstract
Mitochondria are an essential pharmacological target for the development of cytotoxic drugs. Many bioactive agents of plant origin have been found to induce mitochondrial-mediated apoptosis via membrane permeability transition (mPT) pore, osmotic swelling and ultimately the release of cytochrome C. Sarcocephalus latifolius (SL) is used in folkloric medicine for the treatment of breast cancer, but there are no scientific data to support this claim. The study therefore evaluated the in vitro effects of Sarcocephalus latifolius (SL) fruits chloroform (CFSL), ethyl acetate (EFSL), and methanol (MFSL) fractions on rat liver mitochondria. Male Wistar rats with average weight of 90 ± 10 g were used for this study. Rat liver mitochondria were isolated by differential centrifugation. mPT pore opening, mitochondria ATPase activity, Fe2+-induced lipid peroxidation, and cytochrome C release were assayed spectrophotometrically at 540 nm, 660 nm, 532 nm, and 414 nm, respectively. In the absence of Ca2+, CFSL, EFSL, and MFSL induced mPT pore opening in a concentration-dependent manner, with CFSL exhibiting the highest activity. Interestingly, CFSL and EFSL inhibited lipid peroxidation, while MFSL induced lipid peroxidation in a concentration-dependent manner with CFSL showing the highest percentage inhibition of 90%. Mitochondrial ATPase activity and cytochrome C release were significantly enhanced by CFSL. These findings suggest that CFSL and EFSL contain certain bioactive agents that can induce mPT pore opening and subsequently result in mitochondrial-mediated apoptosis. This preliminary finding will serve as a template for drug development for ailments that require the up˗regulation of apoptosis.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
Yang Y, He PY, Zhang Y, Li N. Natural Products Targeting the Mitochondria in Cancers. Molecules. 2021; 26:92. https://doi.org/10.3390/ molecules26010092.
Okullo JBL, Hall JB, Obua J. Leafing, flowering and fruiting of Vitellana paradoxa subsp. Nilotica in savanna parklands in Uganda. Agro Sys. 2004; 60(1):77-91.
World Bank Reports, (2003).
Waseem M and Wang BD. Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight. Int J Mol Sci. 2023; 24:5564. https://doi.org/10.3390/ ijms24065564.
Jeena MT, Sangpil K, Seongeon J, Ja-Hyoung R. Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy. Cancers. 2020; 12(1):4. https://doi.org/10.3390/cancers12010004.
Pfeffer CM amd Singh ATK. Apoptosis: A target for anticancer therapy. Int J Mol Sci. 2018; 19(2):448.
Pena-Blanco A and Garcia-Saez A. Bak, Bax and beyond – mitochondrial performance in apoptosis. The FEBS J. 2018; 285:416-431.
Gang C, Feng W, Dunyaporn T, Peng H. Preferential killing of cancer cells with mitochondrial dysfunction by natural compounds. Mitochondrion. 2010; 10(6):614–625. doi: 10.1016/j.mito.2010.08.001.
Cheung HH, Liu X, Rennert OM. Apoptosis: Reprogramming and the fate of mature cells. ISRN Cell Bio. 2012; 2012:1-8.
Zaman S, Wang R, Gandhi V. Targeting the apoptosis pathway in hematologic malignancies. Leuk Lymphoma. 2014; 55:1980-1992.
Lopez J and Tait SWG. Mitochondrial apoptosis: killing cancer using the enemy within. Br J Cancer. 2015; 112(6):957-962. doi: 10. 1038 ∕ bjc, 85.
Hassan M, Watari H, AbuAlmaaty A, Ohba Y. Sakuraragi N. Apoptosis and molecular targeting therapy in cancer. BioMed Res Int. 2014; 2014:150845. doi: 10.1155/ 2014/150845.
Xiong S, Tianyang M, Guowen W, Xuejun J. Mitochondria-mediated apoptosis in mammals. Protein Cell. 2014; 5(10):737-749. DOI 10.1007/s13238-014-0089-1.
He J, Ford HC, Carroll J, Ding S, Fearnley IM, Walker JE. Persistence of the mitochondrial permeability transition in the absence of subunit c of human ATP synthase. Proc Natl Acad Sci U S A. 2017; 114(13):3409-3414.
Zhou W, Marinelli F, Nief C, Faraldo-Gomez JD. Atomistic simulations indicate the c-subunit ring of the FoF1 ATP synthase is not the mitochondrial permeability transition pore. Elife. 2017; 6:e23781.
Claire MP and Amareshwar TKS. Apoptosis: A Target for Anticancer Therapy. Int J Mol Sci. 2018; 19:448. doi: 10.3390/ijms19020448.
Su GY, Chen ML, Wang KW. Natural New Bioactive Anthraquinones from Rubiaceae. Mini-Rev Org Chem. 2020; 17(7):872–883. https://doi.org/10.2174/1570193x17666200107092510.
Charles-Okhe O, Odeniyi MA, Fakeye TO, Ogbole OO, Akinleye TE, Adeniji AJ. Cytotoxic activity of crude extracts and fractions of African peach (nauclea latifolia smith) stem bark on two cancer cell lines. Phytomed Plus. 2022; 2(1):100212. https://doi.org/10.1016/j.phyplu.2021.100212.
Imah-Harry JU. Influence of solvent fractions of the fruits of Sarcocephalus latifolius (SMITH) Bruce on rat liver mitochondrial–mediated apoptosis. PhD thesis, University of Ibadan, Ibadan, Nigeria, 2021; 328-330 p.
Da FL, Tindano B, Zabre G, Sakira K, Bayala B, Belemtougri RG, Horlait P. Effects of Sarcocephalus latifolius Fruits Extract on Paracetamol-Induced Liver Damage in Wistar Rats. Pharmacol Pharm. 2023; 14(04):112–122. https://doi.org/10.4236/pp.2023.144009.
Ajiboye AT, Asekun OT, Familoni OB. HPLC Profile of Phenolic Contents, Antioxidant and Antidiabetic Activities of Methanolic Extract of the Leaves of Sarcocephalus latifolius (Bruce, Smith) Grown in North Central Geopolitical Zone, Nigeria. Jordan J Chem. 2020; 15(3):103-110. https://doi.org/10.47014/15.3.14.
Leonard DF, Mahamadou B, Albert S, Basile T, Sékou B, Balé B. Effects of Fruits of Aqueous Extract of Sarcocephalus latifolius B. on Gentamicin-Induced Nephrotoxicity in Rats. J Pharm Pharmacol Res. 2023; 07(01):12-19. https://doi.org/10.26502/fjppr.066
Olorunsogo OO and Malomo SO. Sensitivity of oligomycin-inhibited respiration of isolated rat liver mitochondria to perfluidone, a fluorinated arylalkylsulfonamide. Toxicol. 1985; 35(3):231-240.
Nwaechefu OO, Olaolu TD, Akinwunmi IR, Ojezele OO, Olorunsogo OO. Cajanus cajan ameliorated CCl4-induced oxidative stress in Wistar rats via the combined mechanisms of anti-inflammation and mitochondrial-membrane transition pore inhibition. J Ethnopharmacol. 2022; 289:114920.
Lapidus RG and Sokolove PM. The Mitochondria Permeability Transition. J Biol Chem. 1994; 269(29):18931-18936.
Lardy HA and Wellman H. The catalytic effect of 2,4-dinitrophenol on adenosinetriphosphate hydrolysis by cell particles and soluble enzymes. J Biol Chem. 1953; 201:357-370.
Bassir O. Improving the level of nutrition. W Afr J Biol Appl Chem. 1963; 7:32-40.
Ruberto G, Baratta MT, Deans SG, Dorman HJD. Antioxidant and antimicrobial activity of Foeniculum vulgare and Crithmum maritimum essential oils. Planta Med. 2000; 66:687–93.
Kim B and Song YS. Mitochondrial dynamics altered by oxidative stress in cancer .Free. Rad Res. 2016; 50:1065–1070.
Vakifahmetoglu-Norberg H, Ouchida AT, Norberg E. The role of mitochondria in metabolism and cell death. Biochem Biophys Res Commun. 2017; 482, 426–431.
Gogvadze V, Orrenius S, Zhivotovsky B. Multiple pathways of cytochrome c release from mitochondria in apoptosis. Biochim. Biophys Acta Bioenerg. 2006; 1757:639–647.
Galluzzi L, Oliver K, Erik H, Kroemer G, Marincola F. Immunogenic cell death in cancer: concept and therapeutic implications. J Trans Med. 2023; 21:162. https://doi.org/10.1186/s12967-023-04017-6.
Bernardi P and Rasola A. Calcium and Cell Death: The Mitochondrial Connection. In Calcium Signalling and Disease; Springer: Berlin/Heidelberg, Germany, 2007; 45:481–506.
Halestrap AP. What is the mitochondrial permeability transition pore? J Mol Cell Cardiol. 2009; 46:821–831.
Clavier A, Rincheval-Arnold A, Colin J, Mignotte B, Guena I. Apoptosis in Drosophilia: which role for mitochondria? Apoptosis, 2016, 21.3:239-51.
Ferreira CGM, Epping F, Kruyt AE, Giuseppe G. Apoptosis: Target of Cancer Therapy. Clin Can Res; 2002; 8:2024-2034.
Kalkavan H and Green DR. MOMP, cell suicide as a BCL-2 family business: Cell Death Diff. 2018; 25:46–55.
Matsuura K and Kurokawa M. Metabolic Regulation of Apoptosis in Cancer: In Int Rev Cell Mol Biol. 2016; 24.
Adedosu OT, Oyedeji AT, Iwakun T, Ehigie AF, Olorunsogo OO. Hepatoprotective Activity and Inhibitory Effect of Flavonoid –Rich Extract of Brysocarpus Coccineus Leaves on Mitochondrial Membrane Permeability Transition Pore. Asian J Nat Appl Sci, 2014; 3(3):91-100.
Olowofolahan AO, Adeoye AO, Offor GN., Adebisi AO. Induction of Mitochondrial Membrane Permeability Transition Pore and Cytochrome c Release by Different Fractions of Drymaria cordata. Arch. Basic Appl Med. 2015; 3:135-144.
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 Pharmacol. 2017; 8:221-225.
Oyebode OT, Adebusuyi ST, Akintimehin OE, Olorunsogo OO. Modulation of Cytochrome C Release and Opening of Mitochondrial Permeability Transition Pore by Calliandra portoricensis (Benth) Root Bark Methanol Extract. Eur J Med Plant. 2017; 20(1):1-14.
Liang WZ, Chou CT, Chang HT, Cheng JS, Kuo DH, Ko KC, Chiang NN, Wu RF, Shieh P, Jan CR. The mechanism of honokiol-induced intracellular Ca2+ rises and apoptosis in human glioblastoma cells. Chem Biol Int. 2014; 221:13–23.
Rahman MA, Bishayee K, Huh SO. Angelica polymorpha Maxim induces apoptosis of human SH-SY5Y neuroblastoma cells by regulating an intrinsic caspase pathway. Mol Cell. 2016; 39:119–128.
Yang Y, Pi C, Wang G. Inhibition of PI3K/Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells. Biomed Pharmacother. 2018; 103:699–707.
Johnson D and Lardy H. Isolation of liver or kidney mitochondria. Metds. Enzymol. 1967; 10:94-96.
Javadov S, Karmazyn M, Escobales N. Mitochondrial permeability transition pore opening as a promising therapeutic target in cardiac diseases. J Pharmacol Exp Ther. 2009; 330(3):670-678.
Bonora M and Pinton PA. New Current for the Mitochondrial Permeability Transition. Trends Biochem. Sci. 2019; 44:559–561.
Bernadi P, Di Lisa F, Fogolari F, Lippe G. From ATP to PTP and back: a dual function for the mitochondrial ATP synthase. Circ Res. 2015; 116:1850-1862.
Zorov D, Juhaszoova M, Sollott S. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014; 94:909-950.
Shi Y. Emerging roles of cardiolipin remodeling in mitochondrial dysfunction associated with diabetes, obesity and cardiovascular diseases. J Biomed Res. 2010; 24:6-15.
Fiorucci L, Erba F, Santucci R, Sinibaldi F. Cytochrome c Interaction with Cardiolipin Plays a Key Role in Cell Apoptosis: Implications for Human Diseases. Symmetry. 2022; 14(4):767. https://doi.org/10.3390/sym14040767
Szeto HH. First-in class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014; 171(8):2029-2050. http/doi.org/10.1111/bph.12461.
Yesufu HB, Khan IZ, Abdulrahman FI, Abatcha YZ. A survey of the phytochemical and antioxidant potential of the fruit extracts of Sarcocephalus latifolius (Smith) Bruce (Rubiaceae): J Chem Pharm Res. 2014; 6(5):791-795.
Giampaolo M, Carlotta G, Massimo B, Silvia P, Rita P, Mariusz RW., Gianluca C, Paolo P. Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury. J Mol Cell Card. 2015; 78:142–153.