ABSTRACT
The chemoprotective effects of caffeic (CA), chlorogenic (CHA) and rosmarinic (RA) acids were tested against the toxicity of doxorubicin (DOX) in neonatal rat cardiomyocytes and the iron-dependent DOX induced lipid peroxidation of heart membranes, mitochondria and microsomes. The protectivity of these acids was compared with dexrazoxan, used as an adjuvant during DOX chemotherapy. The cytoprotective effects were assessed by enzyme (LDH and ASAT) and troponin I leakage, secondly by intracellular ATP content. All hydroxycinnamic acids proved non-cytotoxic, and they stabilized both membranes and the energetic status of cardiomyocytes. After preincubation of cardiomyocytes with the test compounds (100, 200 microm; 1 h) the cardiomyocytes were treated with the toxic agent, DOX (100 microm; 8 h). The test compounds protected cardiomyocytes against DOX induced oxidative stress (RA > CHA > or = CA) on all monitored parameters. Substantial preservation of monolayer integrity of the cardiomyocytes by test compounds was also found microscopically. All the acids were more effective in the assays used than dexrazoxan. RA showed the most effective cytoprotectivity. All the acids significantly reduced the iron-dependent DOX induced lipid peroxidation of heart membranes, although of the test compounds, CHA was found to be the most effective (IC(50) = 8.04 +/- 0.74/6.87 +/- 0.52 micro m for microsomes/mitochondria).
Subject(s)
Heart Diseases/prevention & control , Phytotherapy , Plant Extracts/pharmacology , Plants, Medicinal , Protective Agents/pharmacology , Animals , Caffeic Acids/administration & dosage , Caffeic Acids/pharmacology , Caffeic Acids/therapeutic use , Chlorogenic Acid/administration & dosage , Chlorogenic Acid/pharmacology , Chlorogenic Acid/therapeutic use , Cinnamates/administration & dosage , Cinnamates/pharmacology , Cinnamates/therapeutic use , Depsides , Doxorubicin , Heart Diseases/chemically induced , Heart Diseases/pathology , Inhibitory Concentration 50 , Lipid Peroxidation/drug effects , Male , Microsomes/drug effects , Mitochondria, Heart/drug effects , Myocardium/cytology , Myocardium/enzymology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/enzymology , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Protective Agents/administration & dosage , Protective Agents/therapeutic use , Rats , Rats, Wistar , Rosmarinic AcidABSTRACT
The organic fraction (OF; 25.7% w/w of rosmarinic acid) of Prunella vulgaris (total extract) was found to exhibit the following: scavenging activity on diphenylpicrylhydrazyl radical (DPPH), inhibition of in vitro human LDL Cu(II)-mediated oxidation, protection of rat mitochondria and rat hepatocytes exposed to either tert-butyl hydroperoxide, or to Cu(II) and Fe(III) ions. OF also showed a potential to inhibit rat erythrocyte haemolysis and it reduced the production of LTB(4) in bovine PMNL generated by the 5-lipoxygenase pathway. Other observations included antiproliferative effects against HaCaT cells and mouse epidermal fibroblasts and a moderate OF antimicrobial activity on gram-positive bacteria. Rosmarinic, caffeic and 3-(3,4-dihydroxyphenyl)lactic acids exhibited less potent activity than the plant extract in all bioassays. The antioxidative, antimicrobial, together with antiviral effects offer good prospects for the medicinal applications of P. vulgaris.