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Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Research Article

Modulatory Potential of Citrus sinensis and Moringa oleifera Extracts and Epiphytes on Rat Liver Mitochondrial Permeability Transition Pore

Author(s): Akinwunmi O. Adeoye*, John A. Falode, Temitope O. Jeje, Praise T. Agbetuyi-Tayo, Sikirat M. Giwa, Yesirat O. Tijani and Damilola E. Akinola

Volume 19, Issue 3, 2022

Published on: 11 April, 2022

Article ID: e150322202238 Pages: 10

DOI: 10.2174/1570163819666220315124507

Price: $65

Abstract

Background: Bioactive agents from medicinal and dietary plants have been reported to modulate the mitochondrial membrane permeability transition pores.

Objective: This study investigated the in vitro effects of C. sinensis (CSE) and M. oleifera (MOE) methanol leaf extracts and their epiphytes (CEP and MEP) on mitochondria permeability transition pores.

Methods: In vitro antioxidant activities of the extracts were determined using standard procedures and quantification of polyphenolic compounds in the extract was done using HPLC-DAD. Opening of the mitochondrial permeability transition pores was assessed as mitochondrial swelling and observed spectrophotometrically as changes in absorbance under succinate-energized conditions. Cytochrome c release was also assessed spectrophotometrically.

Results: From the results, CSE, MOE, CEP, and MEP inhibited lipid peroxidation and scavenged nitric oxide and DPPH radicals in a concentration-dependent manner. All extracts exhibited greater ferric reducing antioxidant potential. More so, the results showed that CSE, MOE, CEP, and MEP possess the substantive amount of total flavonoids and total phenolics. CSE and MOE had higher total flavonoids and total phenolic content when compared with the epiphytes. HPLC-DAD results revealed Tangeretin as the most abundant in CSE; Eriocitrin in citrus epiphytes; Moringine in MOE and Flavones in moringa epiphytes. All extracts inhibited calcium-induced opening of the pores in a concentration- dependent manner, with C. sinensis leaf extract (CSE) and moringa epiphyte (MEP) being the most potent in this regard with no significant release of cytochrome c at all concentrations.

Conclusion: The results suggest that CSE and MEP have bioactive agents, which could be useful in the management of diseases where too much apoptosis occurs characterized by excessive tissue wastage, such as neurodegenerative conditions.

Keywords: Mitochondrial permeability transition, cytochrome C, apoptosis, antioxidant, HPLC-DAD, epiphytes.

Graphical Abstract

[1]
Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 2005; 307(5708): 384-7.
[http://dx.doi.org/10.1126/science.1104343] [PMID: 15662004]
[2]
Bernardi P, Rasola A, Forte M, Lippe G. The mitochondrial permeability transition pore: Channel formation by F-ATP synthase, integration in signal transduction and role in pathophysiology. Physiol Rev 2015; 95(4): 1111-55.
[http://dx.doi.org/10.1152/physrev.00001.2015] [PMID: 26269524]
[3]
Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science 2004; 305(5684): 626-9.
[http://dx.doi.org/10.1126/science.1099320] [PMID: 15286356]
[4]
Busanello ENB, Figueira TR, Marques AC, Navarro CDC, Oliveira HCF, Vercesi AE. Facilitation of Ca2+ -induced opening of the mitochondrial permeability transition pore either by nicotinamide nucleotide transhydrogenase deficiency or statins treatment. Cell Biol Int 2018; 42(6): 742-6.
[http://dx.doi.org/10.1002/cbin.10949] [PMID: 29424467]
[5]
Fulda S. Modulation of apoptosis by natural products for cancer therapy. Planta Med 2010; 76(11): 1075-9.
[http://dx.doi.org/10.1055/s-0030-1249961] [PMID: 20486070]
[6]
Pander J, Heusinkveld M, van der Straaten T, et al. Activation of tumor-promoting type 2 macrophages by EGFR-targeting antibody Cetuximab. Clin Cancer Res 2011; 17(17): 5668-73.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0239] [PMID: 21788356]
[7]
Martin KR. Targeting apoptosis with dietary bioactive agents. Exp Biol Med (Maywood) 2006; 231(2): 117-29.
[http://dx.doi.org/10.1177/153537020623100201] [PMID: 16446487]
[8]
Millimouno FM, Dong J, Yang L, Li J, Li X. Targeting apoptosis pathways in cancer and perspectives with natural compounds from mother nature. Cancer Prev Res (Phila) 2014; 7(11): 1081-107.
[http://dx.doi.org/10.1158/1940-6207.CAPR-14-0136] [PMID: 25161295]
[9]
Piccinelli AL, García MM, Armenteros DM, et al. HPLC-PDA-MS and NMR characterization of C-glycosyl flavones in a hydroalcoholic extract of Citrus aurantifolia leaves with antiplatelet activity. J Agric Food Chem 2008; 56(5): 1574-81.
[http://dx.doi.org/10.1021/jf073485k] [PMID: 18278866]
[10]
Angew ON. Functional foods. Trends Food Sci Technol 2007; 30: 19-21.
[11]
Okwu DE. Phytochemicals and vitamins content of indigenous spices of south eastern nigeria. J Sustainable Agric Environ 2004; 6: 30-7.
[12]
Martin FW, Ruberte RM, Meitzner ES. Edible leaves of the Tropics. 3rd ed. Educational Concerns for Hunger Organization 1998; p. 194.
[13]
Joshi P, Mehta D. Effect of dehydration on the nutritive value of drumstick leaves. J Metabolomics Sys Biol 2010; 1(1): 5-9.
[14]
Devendra C, Leng RA. Feed resources for animals in Asia: issues, strategies for use, intensification and integration for increased productivity. Asian-Australas J Anim Sci 2011; 24(3): 303-21.
[http://dx.doi.org/10.5713/ajas.2011.r.05]
[15]
Patil SD, Jane R. Antimicrobial activity of Moringa oleifera on antitubercular drug-induced liver damage in rats. J Med Food 2013; 1(3): 182-9.
[16]
Pal SK, Mukherjee PK, Saha BP. Studies on the antiulcer activity of Moringa oleifera leaf extract on gastric ulcer models in rats. Phytother Res 1995; 9(6): 463-5.
[http://dx.doi.org/10.1002/ptr.2650090618]
[17]
Sydney EE, Joseph SE, Harold WK. Evaluation of tree canopy epiphytes and bark characteristics associated with the presence of Corticolous myxomycetes. Botany 2009; 87(5): 509-17.
[http://dx.doi.org/10.1139/B09-027]
[18]
Shanavaskhan AE, Sivadasan M, Alfarhan AH, Thomas J. Ethnomedicinal aspects of angiosperms epiphytes and parasites of Kerala, India. Indian J Tradit Knowl 2012; 11(2): 250-8.
[19]
Khan N, Adhami VM, Mukhtar H. Apoptosis by dietary agents for prevention and treatment of prostate cancer. Endocr Relat Cancer 2010; 17(1): R39-52.
[http://dx.doi.org/10.1677/ERC-09-0262] [PMID: 19926708]
[20]
Kumaran A, Karunakaran RJ. In vitro antioxidant activities of methanol extracts of five Phyllanthus species from India. Lebensm Wiss Technol 2007; 40: 344-52.
[http://dx.doi.org/10.1016/j.lwt.2005.09.011]
[21]
Park YS, Jung ST, Kang SG, et al. Antioxidants, and proteins in ethylene-treated kiwifruits. Food Chem 2008; 107(2): 640-8.
[http://dx.doi.org/10.1016/j.foodchem.2007.08.070]
[22]
Molyneux P. The use of stable free radical Diphenylpicryl Hydrazyl (DPPH) for estimating antioxidant activity. J Sci Technol 2004; 26: 212-9.
[23]
Ruberto G, Baratta MT, Deans SG, Dorman HJ. Antioxidant and antimicrobial activity of Foeniculum vulgare and Crithmum maritimum essential oils. Planta Med 2000; 66(8): 687-93.
[http://dx.doi.org/10.1055/s-2000-9773] [PMID: 11199122]
[24]
Oyaizu M. Studies on the product of browning reaction prepared from glucosamine. J Nutr 1986; 44: 307-15.
[25]
Sreejayan N, Rao MN. Nitric oxide scavenging by Curcuminoids. J Pharm Pharmacol 1997; 49(1): 105-7.
[http://dx.doi.org/10.1111/j.2042-7158.1997.tb06761.x] [PMID: 9120760]
[26]
Johnson D, Lardy H. Isolation of liver or kidney mitochondria. Methods Enzymol 1967; 10: 94-6.
[http://dx.doi.org/10.1016/0076-6879(67)10018-9]
[27]
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[28]
Lapidus RG, Sokolove PM. Spermine inhibition of the permeability transition of isolated rat liver mitochondria: An investigation of mechanism. Arch Biochem Biophys 1993; 306(1): 246-53.
[http://dx.doi.org/10.1006/abbi.1993.1507] [PMID: 8215411]
[29]
Appaix F, Minatchy M, Riva-Lavieille C, Olivares J, Antonsson B, Saks VA. Rapid spectrophotometric method for quantitation of cytochrome c release from isolated mitochondria or permeabilized cells revisited. Biochim Biophys Acta 2000; 1457(3): 175-81.
[http://dx.doi.org/10.1016/S0005-2728(00)00098-0] [PMID: 10773162]
[30]
Tanaka T, Makita H, Kawabata K, et al. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin. Carcinogenesis 1997; 18(5): 957-65.
[http://dx.doi.org/10.1093/carcin/18.5.957] [PMID: 9163681]
[31]
Abd Rani NZ, Husain K, Kumolosasi E. Moringa genus: A review of phytochemistry and pharmacology. Front Pharmacol 2018; 9: 108.
[http://dx.doi.org/10.3389/fphar.2018.00108] [PMID: 29503616]
[32]
Adeoye AO, Olanlokun JO, Bewaji CO. Activity of apigenin and quercetin on rat hepatic mitochondrial permeability transition pore. Pharmacologyonline 2018; 2: 11-22.
[33]
Daniel OO, Adeoye AO, Ojowu J, Olorunsogo OO. Inhibition of liver mitochondrial membrane permeability transition pore opening by quercetin and vitamin E in streptozotocin-induced diabetic rats. Biochem Biophys Res Commun 2018; 504(2): 460-9.
[http://dx.doi.org/10.1016/j.bbrc.2018.08.114] [PMID: 30195498]

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