The triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA3), attenuates high glucose-induced oxidative damage and apoptosis by improving energy metabolism.

Autor: Sangweni NF; Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg 7505, South Africa; Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa. Electronic address: nonhlakanipho.sangweni@mrc.ac.za., Mosa RA; Department of Biochemistry, Genetics and Microbiology (BGM), Division of Biochemistry, University of Pretoria, Hatfield 0028, South Africa., Dludla PV; Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg 7505, South Africa; Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, Italy. Electronic address: phiwayinkosi.dludla@mrc.ac.za., Kappo AP; Department of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park 2006, South Africa., Opoku AR; Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa., Muller CJF; Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg 7505, South Africa; Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa; Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa. Electronic address: christo.muller@mrc.ac.za., Johnson R; Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg 7505, South Africa; Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa. Electronic address: rabia.johnson@mrc.ac.za.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2021 May; Vol. 85, pp. 153546. Date of Electronic Publication: 2021 Mar 10.
DOI: 10.1016/j.phymed.2021.153546
Abstrakt: Background: Hyperglycemia-induced cardiovascular dysfunction has been linked to oxidative stress and accelerated apoptosis in the diabetic myocardium. While there is currently no treatment for diabetic cardiomyopathy (DCM), studies suggest that the combinational use of anti-hyperglycemic agents and triterpenes could be effective in alleviating DCM.
Hypothesis: To investigate the therapeutic effect of methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA3), in the absence or presence of the anti-diabetic drug, metformin (MET), against hyperglycemia-induced cardiac injury using an in vitro H9c2 cell model.
Methods: To mimic a hyperglycemic state, H9c2 cells were exposed to high glucose (HG, 33 mM) for 24 h. Thereafter, the cells were treated with RA3 (1 μM), MET (1 μM) and the combination of MET (1 μM) plus RA3 (1 μM) for 24 h, to assess the treatments therapeutic effect.
Results: Biochemical analysis revealed that RA3, with or without MET, improves glucose uptake via insulin-dependent (IRS-1/PI3K/Akt signaling) and independent (AMPK) pathways whilst ameliorating the activity of antioxidant enzymes in the H9c2 cells. Mechanistically, RA3 was able to alleviate HG-stimulated oxidative stress through the inhibition of reactive oxygen species (ROS) and lipid peroxidation as well as the reduced expression of the PKC/NF-кB cascade through decreased intracellular lipid content. Subsequently, RA3 was able to mitigate HG-induced apoptosis by decreasing the activity of caspase 3/7 and DNA fragmentation in the cardiomyoblasts.
Conclusion: RA3, in the absence or presence of MET, demonstrated potent therapeutic properties against hyperglycemia-mediated cardiac damage and could be a suitable candidate in the prevention of DCM.
(Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE
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