The Cardioprotective effect of a Lanosteryl Triterpene from Protorhus Longifolia on H9c2 Cardiomyoblasts
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Date
2017
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University of Zululand
Abstract
Introduction: Diabetes mellitus is a predisposing factor of cardiovascular diseases (CVDs). Globally, CVDs are the prominent cause of death in both diabetic and nondiabetic individuals. In an effort to fight the disease burden, more researchers are looking into natural-products as adjunctive therapies to use with the current treatment regimen against diabetes and concomitant cardiovascular complications. For decades, herbalists in the Zululand region of KwaZulu-Natal have been using Protorhus longifolia as a blood-thinning agent. Recently, Mosa and colleagues have demonstrated that methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA3) derived from the stem barks of P. longifolia can act as a nutraceutical to control hyperglycemia, hyperlipidemia and reduce insulin resistance in a diabetic animal model. However, no mechanism associated with its cardioprotective potential has been proposed. Aim: In this study, we aimed to assess the mechanism by which methyl-3βhydroxylanosta-9,24-dien-21-oate (RA3) is able to improve glucose uptake, whilst decreasing lipotoxicity, oxidative stress, insulin resistance and apoptosis in H9c2 cardiomyoblasts exposed to high glucose.
Methodology: H9c2 cardiomyoblasts were cultured in either normal (NG- 5.5 mM) or high (HG- 33 mM) glucose for 24 hrs. Subsequently, cells exposed to HG were treated with RA3 (1 μM), n-acetyl cysteine (NAC, 1 mM), metformin (MET, 1 μM), a combination of MET+RA3 (both at 2 μM) as well as MET+NAC (at 2μM and 2 mM, respectively) for a further 24 hrs. Time and dose response as well metabolic activity were assessed using ATP assays. While, the cardioprotective potential of RA3 to attenuate high glucose induced, shift in substrate preference, where investigated using various biochemical assays and protein expression analysis. Results: Data from this study accentuated the anti-diabetic properties of RA3 through its ability to improve shift in substrate preference and insulin signaling in the H9c2 cardiomyoblasts. We further demonstrated the capability of RA3 to mitigate high glucose induced oxidative stress and accelerated apoptosis in these cells. Interestingly the results from this study showed a synergistic cardioprotective effect with the treatment of MET+RA3. However, the combination of MET+NAC was not as effective as MET alone to alleviate high-glucose-induced cardiac dysfunction.Conclusion: Data presented in this study provides a plausible mechanism by which RA3 protects the myocardium against hyperglycemic-induced oxidative stress and apoptosis.
Description
A dissertation submitted to the Faculty of Science and Agriculture in fulfillment of the requirements for the Degree of Master Of Science in Biochemistry in the Department of Biochemistry and Microbiology at the University Of Zululand, 2017
Keywords
cardioprotective effects --diabetes mellitus --cardiovascular diseases