trilinolein and Cardiomegaly

Trilinolein, isolated from the traditional Chinese herb Sanchi ( Panax notoginseng), has been shown to have myocardial protective effects via its antioxidant ability. However, the cellular and molecular mechanisms of the protective effect of trilinolein in the heart remain to be elucidated. Oxidative mechanisms have been implicated in neonatal cardiomyocyte hypertrophy. We therefore have examined whether trilinolein attenuates reactive oxygen species (ROS) production and thus ET-1-induced hypertrophy of cardiomyocytes. Cultured neonatal rat cardiomyocytes were stimulated with ET-1 (10 nM), [3H]leucine incorporation and the beta-myosin heavy chain (beta-MyHC) promoter activity were examined. Trilinolein (1 and 10 microM) inhibited the ET-1-induced increase of [3H]-leucine incorporation in a concentration-dependent manner. Trilinolein (1 and 10 microM) also inhibited ET-1-induced beta-MyHC promoter activity in cardiomyocytes. We further examined the effects of trilinolein on ET-1-induced intracellular ROS generation by measuring a redox-sensitive fluorescent dye, 2',7'-dichlorofluorescin diacetate, fluorescence intensity. Trilinolein (1 and 10 microM) inhibited ET-1-increased intracellular ROS levels in a concentration-dependent manner. This increase of ROS by ET-1 (10 nM) or H2O2 (25 microM) was significantly inhibited by trilinolein (10 microM) and N-acetylcysteine (10 mM). Moreover, ET-1- or H2O2-induced beta-MyHC promoter activity and protein synthesis were also inhibited by trilinolein (10 microM). These data indicate that trilinolein inhibits ET-1-induced beta-MyHC promoter activity, and subsequent hypertrophy via its antioxidant ability in cardiomyocytes.

Topics: Animals; Animals, Newborn; Cardiomegaly; Cardiotonic Agents; Dose-Response Relationship, Drug; Endothelin-1; Free Radical Scavengers; Myocytes, Cardiac; Myosin Heavy Chains; Panax; Phytotherapy; Plant Extracts; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; Triglycerides

The myocardial protective effects of trilinolein, isolated from the Chinese herb Sanchi (Panax notoginseng), may be related to its antioxidant effects. In the present study, we investigated the effects of trilinolein on angiotensin II-induced cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were stimulated with angiotensin II, [3H]leucine incorporation and the beta-myosin heavy chain promoter activity were examined. We also examined the effects of trilinolein on angiotensin II-induced intracellular reactive oxygen species generation. Trilinolein significantly inhibited angiotensin II-increased protein synthesis, beta-myosin heavy chain promoter activity, and intracellular reactive oxygen species generation. Antioxidant N-acetylcysteine also decreased angiotensin II-increased protein synthesis and beta-myosin heavy chain promoter activity. Furthermore, trilinolein and N-acetylcysteine decreased angiotensin II- or hydrogen peroxide (H2O2)-activated mitogen-activated protein kinases (MAPKs) phosphorylation, and activator protein-1 (AP-1)- [or nuclear factor-kappaB (NF-kappaB)]-reporter activities. These data indicate that trilinolein inhibits angiotensin II-induced cardiomyocyte hypertrophy and beta-myosin heavy chain promoter activity via attenuation of reactive oxygen species generation.

Topics: Angiotensin II; Animals; Cardiomegaly; Cells, Cultured; Dose-Response Relationship, Drug; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Triglycerides