The Cardioprotective Effects of Citric Acid and L-Malic Acid on Myocardial Ischemia/Reperfusion Injury

Abstract

Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components of Fructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. In in vivo rat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation. In vitro experiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient of Fructus Choerospondiatis responsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease.

Antioxidant property and α $$ \boldsymbol{\upalpha} $$ -glucosidase, α $$ \boldsymbol{\upalpha} $$ -amylase and lipase inhibiting activities of Flacourtia inermis fruits: characterization of malic acid as an inhibitor of the enzymes

“…It has been suggested that cranberry (Vaccinium macrocarpon) fruit powders, containing organic acids, as well as polyphenolic compounds including phenolic acids and displaying inhibition of both α-glucosidase and α-amylase, could be developed for the management of postprandial hyperglycemia (Pinto et al 2010). In a study of organic acids in Chinese herbs, it was found that organic acids such as citric acid and L-malic acid may be the active ingredients responsible for the cardioprotective effects Fructus choerospondiatis (Tang et al 2013).…”

The Cardioprotective Effect of Protocatechuic Acid on Myocardial Ischemia/Reperfusion Injury

“…Diltiazem, a selective L-type Ca 2+ -channel blocker, has been reported to be effective in treating myocardial infarction diseases (15). Clopidogrel, a thienopyridine derivative, and a selective and irreversible antagonist of ADP (P2Y 12 ) receptor, is a commonly used drug in the treatment of ischemic heart disease (20 -22).…”

“…The measurement of infarct size using N-BT staining was identical to the method described previously (15). The rats were then sacrificed at the end of 2-h reperfusion.…”

Effects of L-Malic Acid on Alpha-Glucosidase: Inhibition Kinetics and Computational Molecular Dynamics Simulations

“…The MA supplementation could be a promising treatment for the calcium oxalate stone disease due to its capacity to increase urinary citrate excretion and urinary pH [8]. MA has protective effects on myocardial ischemia/reperfusion injury due to its anti-inflammatory, anti-platelet aggregation, and direct cardiomyocyte protective effects [9].…”