RESUMEN
Previous studies have demonstrated that DNA damage induces atherosclerosis and that oxidative stress has an important role in DNA damage. Gypenosides (Gps), the main ingredient of Gynostemma Pentaphylla (Thunb.) Makino, have been recognized as specific antioxidants and have previously been reported to inhibit highfat dietinduced atherosclerosis in rats. However, whether or not Gps attenuate DNA damage through their antioxidant effects remains to be elucidated. The current study was performed to clarify whether or not Gps can inhibit cholesterolinduced DNA damage through antioxidation. The present study provided new insights into the pharmacological effects of Gps on atherosclerosis. HUVECs were treated with Gps at various concentrations (1, 10 and 100 µg/ml) for 1 h. The protective effects of Gps on cholesterolinduced DNA damage were determined using immunofluorescence, western blotting, reversetranscription quantitative polymerase chain reaction and flow cytometry. Pretreatment with Gps (1, 10 and 100 µg/ml) effectively attenuated cholesterolinduced DNA damage in HUVECs by inhibiting phosphorylation of H2AX, a member of the histone family. Furthermore, Gps (100 µg/ml) pretreatment inhibited cholesterolinduced transcription and activity of nicotinamide adenine dinucleotide phosphateoxidase 4 and reduced intracellular ROS levels. In conclusion, Gps attenuated cholesterolinduced DNA damage by inhibiting ROS production in HUVECs, suggesting that the inhibitory effect of Gps on atherogenesis is correlated with the alleviation of DNA damage.
Asunto(s)
Colesterol/farmacología , Daño del ADN/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/química , Antioxidantes/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Gynostemma/química , Histonas/metabolismo , Humanos , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Óxido Nítrico Sintasa/metabolismo , Estrés Oxidativo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Xantina Oxidasa/metabolismoRESUMEN
OBJECTIVE: To evaluate the effect and possible mechanism of gypenoside (GP) on expression of inflammatory factors in aortic lesion of rats with high-fat induced atherosclerosis. METHODS: Atherosclerotic rat model was established by feeding high-fat diet and intraperitoneal injection of vitamin D3. Sixty healthy male SD rats were randomly divided into the normal group, the model group, the simvastatin treated group and the three GP groups treated respectively with different dosages of GP. Rats were sacrificed 7 weeks later, their histopathological changes in thoracic aorta were observed by light microscope; expressions of intercellular adhesion molecule 1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1) and nuclear factor-kappaBp65 (NF-kappaBp65) in aortic wall were detected by immunohistochemistry; serum level of oxidized low-density lipoprotein (ox-LDL) was determined by ELISA; serum total antioxidant capacity determined by colorimetry, and serum malondialdehyde (MDA) level determined by Thiobarbituric acid method. RESULTS: In comparing with the model group, GPS showed actions in lessening the atherosclerosis lesion; reducing expressions of ICAM-1, MCP-1 and NF-kappaBp65 in aortic wall (P<0.01) and serum levels of MDA, ox-LDL (P < 0.01), as well as increasing the serum level of total antioxidant capacity (P < 0.01 ). CONCLUSION: GP can down-regulate the expressions of ICAM-1 and MCP-1, inhibit the atherosclerosis formation in experimental rats, its mechanism might be related with its anti-oxidation effect and further inhibiting on the NF-kappaB activation.
Asunto(s)
Aterosclerosis/metabolismo , Estrés Oxidativo , Animales , Aterosclerosis/patología , Quimiocina CCL2/metabolismo , Gynostemma , Inflamación , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To study the effect of hesperidin and rutin on oxidative modification of high density lipoprotein (HDL) in vitro. METHODS: HDL was isolated from healthy human plasma by sequential ultracentrifugation, and was oxidized by copper ions. The inhibitory effects of hesperidin and rutin on HDL oxidative modification were valued by the formation of malondialdehyde (MDA). RESULTS: Hesperidin and rutin significantly inhibited copper-induced oxidation of HDL in a dose-dependent manner. CONCLUSION: Both hesperidin and rutin can prevent HDL from copper-induced oxidative modification in vitro. This result suggests that they might have antiatherogenic effect.