title: 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.
authors.affiliation: Institute for Biomedical Research, Academy of Medicine, Lithuanian University of Health Sciences, Eiveniu 4, LT-50009, Kaunas, Lithuania.
authors.forename: Julius
authors.initials: J
authors.lastname: Liobikas
authors.forename: Daiva
authors.initials: D
authors.lastname: Majiene
authors.forename: Sonata
authors.initials: S
authors.lastname: Trumbeckaite
authors.forename: Lolita
authors.initials: L
authors.lastname: Kursvietiene
authors.forename: Ruta
authors.initials: R
authors.lastname: Masteikova
authors.forename: Dalia M
authors.initials: DM
authors.lastname: Kopustinskiene
authors.forename: Arunas
authors.initials: A
authors.lastname: Savickas
authors.forename: Jurga
authors.initials: J
authors.lastname: Bernatoniene
mesh_terms: D000368:Aged; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D006861:Hydrogen Peroxide; D014315:Triterpenes; D000097245:Ursolic Acid