Abstract
Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is one of the major components of some traditional medicinal herbs, and possesses a wide range of biological functions, such as anti-inflammatory, anticancer, and antioxidative activities. Furthermore, UA may also possess pro-cardiac activities, and is generally present at 1.6–5 ng/mL concentration in commercial herbal preparations produced by pharmaceutical companies. There are several indirect suggestions that cardioprotective effect of UA may involve mitochondria, however the mechanism of action is still not known. Therefore, we investigated the effect of 0.4–200 ng/mL UA on the functions of isolated rat heart mitochondria oxidizing either pyruvate and malate, succinate or palmitoyl-L-carnitine plus malate. We found that starting only from 1.6 to 200 ng/mL UA induced a statistically significant uncoupling of oxidative phosphorylation with all used substrates. We revealed a statistically significant decrease in H2O2 production in mitochondria after incubation with 5 ng/mL of UA. This effect was comparable to the effectiveness of classical uncoupler CCCP. We propose that mild mitochondrial uncoupling induced by pharmacological concentrations of UA from herbal preparations could be one of the beneficial effects of this triterpenoid as a cardioprotective compound.
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