ABSTRACT
Cornelian cherry (Cornus mas L.) fruits have been used in traditional cuisine and in folk medicine in various countries. This study was conducted to evaluate the constituents and impact of cornelian cherry (C. mas L.) fruits lyophilisate on lipid levels, PPARα protein expression, atheromatous changes in the aorta, oxido-redox state, and proinflammatory cytokines in hypercholesterolemic rabbits. The HPLC-MS method was used for determining active constituents in cornelian cherry. In a subsequent in vivo study the protective effect of the cornelian cherry on diet-induced hyperlipidemia was studied using a rabbit model fed 1% cholesterol. Cornelian cherry (100mg/kg b.w.) or simvastatin (5mg/kg b.w.) were administered orally for 60 days. Two iridoids - loganic acid and cornuside - and five anthocyanins were identified as the main constituents of the cornelian cherry. The administering of the cornelian cherry led to a 44% significant decrease in serum triglyceride levels, as well as prevented development of atheromatous changes in the thoracic aorta. Cornelian cherry significantly increased PPARα protein expression in the liver, indicating that its hypolipidemic effect may stem from enhanced fatty acid catabolism. Simvastatin treatment did not affect PPAR-α expression. Moreover, the cornelian cherry had a significant protective effect on diet-induced oxidative stress in the liver, as well as restored upregulated proinflammatory cytokines serum levels. In conclusion, we have shown loganic acid to be the main iridoid constituent in the European cultivar of the cornelian cherry, and proven that the cornelian cherry could have protective effects on diet-induced hypertriglicerydemia and atherosclerosis through enhanced PPARα protein expression and via regulating oxidative stress and inflammation.
Subject(s)
Anthocyanins/pharmacology , Atherosclerosis/drug therapy , Cornus/chemistry , Hypertriglyceridemia/drug therapy , Iridoids/pharmacology , PPAR alpha/metabolism , Animals , Aorta, Thoracic/drug effects , Fruit/chemistry , Inflammation/drug therapy , Lipid Peroxidation , Liver/drug effects , Liver/metabolism , Molecular Structure , Oxidative Stress/drug effects , Rabbits , Triglycerides/bloodABSTRACT
Cyclophosphamide (CPX) is an anticancer drug with immunosuppressive properties. Its adverse effects are partly connected to the induction of oxidative stress. Some studies indicate that water-soluble derivative of morin-morin-5'-sulfonic acid sodium salt (NaMSA) exhibits strong antioxidant activity. The aim of present study was to evaluate the effect of NaMSA on CPX-induced changes in oxido-redox state in rat. Experiment was carried out on Wistar rats divided in three experimental groups (N = 12) receiving: 0.9% saline, CPX (15 mg/kg) or CPX (15 mg/kg) + NaMSA (100 mg/kg), respectively, and were given intragastrically for 10 days. Malondialdehyde (MDA) and glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were determined in liver and kidneys. Catalase (CAT) activity was assessed only in liver. Treatment with CPX resulted in significant decrease in MDA level in both tissues, which was completely reversed by NaMSA treatment only in liver. In comparison to the control group significant decrease in SOD activity were observed in both tissues of CPX receiving group. In kidneys this parameter was fully restored by NaMSA administration. CPX evoked significant decrease in GSH concentration in kidneys, which was completely reversed by NaMSA treatment. No significant changes were seen in GSH levels and CAT activity between all groups in liver. Results of our study suggest that CPX may exert significant impact on oxido-redox state in both organs. NaMSA fully reversed the CPX-induced changes, especially MDA level in liver, SOD activity and GSH concentration in kidneys and it may be done by enhancement of activity/concentration of endogenous antioxidants.
Subject(s)
Antioxidants/pharmacology , Flavonoids/pharmacology , Kidney/drug effects , Liver/drug effects , Oxidative Stress/drug effects , Sulfonic Acids/pharmacology , Animals , Antineoplastic Agents , Catalase/metabolism , Cyclophosphamide , Female , Glutathione/metabolism , Immunosuppressive Agents , Kidney/metabolism , Liver/metabolism , Male , Malondialdehyde/metabolism , Oxidation-Reduction , Rats , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
Asymmetric dimethylarginine (ADMA) is an endogenous methylated amino acid derived from arginine which can inhibit the activity of nitric oxide synthases. In various pathological states such as hypercholesterolemia, hyperglycemia, hyperhomocysteinemia, hypertension, coronary artery disease, heart failure, and stroke, plasma levels of ADMA may be increased and lead to inhibition of NO synthesis and endothelial dysfunction. Inhibition of ADMA synthesis or intensification of metabolism of this compound might indirectly lower ADMA. Antioxidants, estrogen, vitamin A, angiotensin converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and also some hypolipemic, hypoglycemic and beta-adrenoreceptor blocking drugs decrease ADMA levels. In some situations like neurological disorders, decreased plasma levels of ADMA are noticed and drugs increasing the concentration of this compound could exert protective effects. It is reasonable to explore which drugs can increase or decrease ADMA levels and what their mechanism of that action is.
