Uncoupling and Antioxidant Effects of Ursolic Acid in Isolated Rat Heart Mitochondria

Abstract

Ursolic acid (1), a pentacyclic triterpene acid, is one of the major components of certain traditional medicinal plants and possesses a wide range of biological effects, such as anti-inflammatory, antioxidative, and cytotoxic activities. Furthermore, 1, when present at 1.6-5 ng/mL concentrations in commercial herbal preparations used for patients with cardiac disorders, may also exert pro-cardiac activities. There are several indirect suggestions that the cardioprotective mechanism of ursolic acid could involve the mitochondria; however the mechanism of action is still not known. Therefore, the effects of 0.4-200 ng/mL ursolic acid (1) on the functions of isolated rat heart mitochondria oxidizing either pyruvate and malate, succinate, or palmitoyl-l-carnitine plus malate were investigated. It was found that 1 induced a statistically significant uncoupling of oxidative phosphorylation. A statistically significant decrease in H₂O₂ production in the mitochondria was observed after incubation with 5 ng/mL 1. This effect was comparable to the effectiveness of the classical uncoupler carbonyl cyanide 3-chlorophenylhydrazone. Since mild mitochondrial uncoupling has been proposed as one of the mechanisms of cardioprotection, the present results indicate that ursolic acid (1) has potential use as a cardioprotective compound.

Ursolic-Acid-Enriched Herba Cynomorii Extract Protects against Oxidant Injury in H9c2 Cells and Rat Myocardium by Increasing Mitochondrial ATP Generation Capacity and Enhancing Cellular Glutathione Redox Cycling, Possibly through Mitochondrial Uncoupling

“…Mitochondrial uncoupling can be induced by chemical uncouplers as well as by activating uncoupling proteins (UCPs) [30], with resultant increases in oxygen consumption secondary to an increase in electron transport [31]. UA, the major component of HCY2, was found to induce mitochondrial uncoupling in isolated rat heart mitochondria [32]. Such an uncoupling effect produced by the UA-enriched HCY2 could stimulate electron transport in mitochondria, thereby enhancing ATP-GC, which was measured under optimal experimental conditions.…”

Mitochondrial reactive oxygen species production mediates ursolic acid-induced mitochondrial uncoupling and glutathione redox cycling, with protection against oxidant injury in H9c2 cells

“…10,11 Recently, Liobikas et al have suggested that the cardioprotective effect of UA is closely related to its antioxidative activity, with the possible involvement of uncoupling of mitochondrial oxidative phosphorylation. 12 Since mild mitochondrial uncoupling can reduce the extent of mitochondrial ROS production, 13 the direct uncoupling effect of UA, as shown by Liobikas et al in isolated rat heart mitochondria, may therefore reduce the mitochondrial production of H 2 O 2 . 12 However, the biochemical basis underlying the mitochondrial uncoupling produced by UA and whether the mitochondrial uncoupling is the only mechanism responsible for its protection against oxidative stress remain unclear.…”

Inhibitory effect of ursolic acid and oleanolic acid from Eriobotrya fragrans on A549 cell viability in vivo

“…UA and OA have been isolated from and identified in Eriobotrya japonica, and also in plants including Rosmarinus offıcinalis and Glechoma hederaceae (Liu, 1995). The pharmacological properties of OA and UA include anti-oxidative effects (Liobikas et al, 2011;Checker et al, 2012), anti-allergic effects (Kim et al, 2009), hepatic and neural protection (Li et al, 2013), anti-inflammatory effects (Sultana and Saify, 2012), and anti-tumor activity (Wang et al, 2011). Pentacyclic triterpenoids are present at high concentration in loquat leaves.…”