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Opening of liver mitochondrial permeability transition pore in streptozotocin-induced diabetic rats and its inhibition by methanol fraction of Ficus mucoso (Welw) root bark.
J Integr Med. 2019 Nov; 17(6):446-454.JI

Abstract

OBJECTIVE

Several pathologies arise from the inappropriate opening of the mitochondrial permeability transition (mPT) pore. In this regard, inhibition of mPT pore represents a cytoprotective approach to preserve mitochondrial function for treatment of diseases characterized by excessive tissue wastage such as diabetes mellitus. The aim of this study, therefore, was to study the effects of fractions of Ficus mucoso, a medicinal plant used in the traditional treatment of diabetes, on mPT pore in normal and streptozotocin (STZ)-induced diabetic rat liver.

METHODS

Different solvent fractions of the crude methanol extract of F. mucoso were obtained by vacuum liquid chromatography and were tested on the mPT pore. Of all the fractions tested, methanol fraction of F. mucoso (MFFM) was the most potent and was used for in vivo studies. Diabetes mellitus was induced by a single intraperitoneal injection of 60 mg/kg STZ, while treatment lasted for 14 d. In vivo, 30 male Wistar rats were divided into five groups: A, normo-glycemic control (distilled water); B, STZ (65 mg/kg; diabetic control); C, STZ + MFFM (25 mg/kg); D, STZ + MFFM (50 mg/kg); E, STZ + glibenclamide (5 mg/kg). The mPT, mitochondrial ATPase activity, lipid peroxidation and cytochrome c release were assessed spectrophotometrically while blood glucose levels were monitored using glucometer.

RESULTS

In vitro, the solvent fractions of F. mucoso, at all concentrations tested, had no effect on the mPT pore, in the absence of calcium, with no significant release of cytochrome c. Interestingly, calcium-dependent pore opening was inhibited by all solvent fractions of F. mucoso, with the MFFM having the highest inhibitory effect of 83% at 3 mg/mL. Induction of opening of the mPT pore, significant (P < 0.001) enhancement of mitochondrial ATPase activity and elevated malondialdehyde (MDA) levels in STZ-induced diabetes were significantly (P < 0.001) reversed by MFFM and were comparable with the effects of glibenclamide, a standard antidiabetic drug. Also, treatment with MFFM at different doses significantly (P < 0.001) reduced high serum blood glucose compared to the diabetic control.

CONCLUSION

F. mucoso could be useful in therapeutic management of diabetes mellitus given its ability to prevent excessive tissue wastage via inhibition of pore opening, and reduction in levels of MDA and serum blood glucose.

Authors+Show Affiliations

Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria. Electronic address: ot.oyebode@mail.ui.edu.ng.Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria.Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31706863

Citation

Oyebode, Olubukola Titilope, et al. "Opening of Liver Mitochondrial Permeability Transition Pore in Streptozotocin-induced Diabetic Rats and Its Inhibition By Methanol Fraction of Ficus Mucoso (Welw) Root Bark." Journal of Integrative Medicine, vol. 17, no. 6, 2019, pp. 446-454.
Oyebode OT, Ogunbiyi FO, Olorunsogo OO. Opening of liver mitochondrial permeability transition pore in streptozotocin-induced diabetic rats and its inhibition by methanol fraction of Ficus mucoso (Welw) root bark. J Integr Med. 2019;17(6):446-454.
Oyebode, O. T., Ogunbiyi, F. O., & Olorunsogo, O. O. (2019). Opening of liver mitochondrial permeability transition pore in streptozotocin-induced diabetic rats and its inhibition by methanol fraction of Ficus mucoso (Welw) root bark. Journal of Integrative Medicine, 17(6), 446-454. https://doi.org/10.1016/j.joim.2019.10.001
Oyebode OT, Ogunbiyi FO, Olorunsogo OO. Opening of Liver Mitochondrial Permeability Transition Pore in Streptozotocin-induced Diabetic Rats and Its Inhibition By Methanol Fraction of Ficus Mucoso (Welw) Root Bark. J Integr Med. 2019;17(6):446-454. PubMed PMID: 31706863.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Opening of liver mitochondrial permeability transition pore in streptozotocin-induced diabetic rats and its inhibition by methanol fraction of Ficus mucoso (Welw) root bark. AU - Oyebode,Olubukola Titilope, AU - Ogunbiyi,Foluso Olayemi, AU - Olorunsogo,Olufunso Olabode, Y1 - 2019/10/16/ PY - 2019/01/22/received PY - 2019/05/13/accepted PY - 2019/11/11/pubmed PY - 2020/6/9/medline PY - 2019/11/11/entrez KW - Cytochrome c KW - Ficus mucoso KW - Mitochondria KW - Permeability transition SP - 446 EP - 454 JF - Journal of integrative medicine JO - J Integr Med VL - 17 IS - 6 N2 - OBJECTIVE: Several pathologies arise from the inappropriate opening of the mitochondrial permeability transition (mPT) pore. In this regard, inhibition of mPT pore represents a cytoprotective approach to preserve mitochondrial function for treatment of diseases characterized by excessive tissue wastage such as diabetes mellitus. The aim of this study, therefore, was to study the effects of fractions of Ficus mucoso, a medicinal plant used in the traditional treatment of diabetes, on mPT pore in normal and streptozotocin (STZ)-induced diabetic rat liver. METHODS: Different solvent fractions of the crude methanol extract of F. mucoso were obtained by vacuum liquid chromatography and were tested on the mPT pore. Of all the fractions tested, methanol fraction of F. mucoso (MFFM) was the most potent and was used for in vivo studies. Diabetes mellitus was induced by a single intraperitoneal injection of 60 mg/kg STZ, while treatment lasted for 14 d. In vivo, 30 male Wistar rats were divided into five groups: A, normo-glycemic control (distilled water); B, STZ (65 mg/kg; diabetic control); C, STZ + MFFM (25 mg/kg); D, STZ + MFFM (50 mg/kg); E, STZ + glibenclamide (5 mg/kg). The mPT, mitochondrial ATPase activity, lipid peroxidation and cytochrome c release were assessed spectrophotometrically while blood glucose levels were monitored using glucometer. RESULTS: In vitro, the solvent fractions of F. mucoso, at all concentrations tested, had no effect on the mPT pore, in the absence of calcium, with no significant release of cytochrome c. Interestingly, calcium-dependent pore opening was inhibited by all solvent fractions of F. mucoso, with the MFFM having the highest inhibitory effect of 83% at 3 mg/mL. Induction of opening of the mPT pore, significant (P < 0.001) enhancement of mitochondrial ATPase activity and elevated malondialdehyde (MDA) levels in STZ-induced diabetes were significantly (P < 0.001) reversed by MFFM and were comparable with the effects of glibenclamide, a standard antidiabetic drug. Also, treatment with MFFM at different doses significantly (P < 0.001) reduced high serum blood glucose compared to the diabetic control. CONCLUSION: F. mucoso could be useful in therapeutic management of diabetes mellitus given its ability to prevent excessive tissue wastage via inhibition of pore opening, and reduction in levels of MDA and serum blood glucose. SN - 2095-4964 UR - https://www.unboundmedicine.com/medline/citation/31706863/Opening_of_liver_mitochondrial_permeability_transition_pore_in_streptozotocin_induced_diabetic_rats_and_its_inhibition_by_methanol_fraction_of_Ficus_mucoso__Welw__root_bark_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2095-4964(19)30099-8 DB - PRIME DP - Unbound Medicine ER -