RESUMEN
BACKGROUND: NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in the development of atherosclerosis and several studies have suggested that inhibiting NLRP3 inflammasome could be a potential therapeutic approach to treat atherosclerosis. Baicalin is a flavone glycoside with anti-inflammation, anti-oxidative activities. The inhibition of NLRP3 inflammasome activation by baicalin has also been described. Therefore, the effects of baicalin on NLRP3 inflammasome activation and atherosclerosis were evaluated in present study. METHODS: We established the apolipoprotein E-deficient atherosclerosis mice model. After baicalin treatment, the IL-1, IL-18, and reactive oxygen species (ROS) production, and the plaque area was monitored. We also measured the NLRP3, ASC, caspase-1, ICAM-1, and VCAM-1 expression in atherosclerosis mice after baicalin treatment. We silenced NLRP3 by administration of lentivirus expressing NLRP3 shRNA to atherosclerosis mice and monitored the IL-1, IL-18, and ROS production, and NLRP3 inflammasome activation. RESULTS: Baicalin remarkably inhibited the production of IL-1, IL-18, mitochondria ROS, total ROS, ICAM-1, and VCAM-1. Baicalin reduced the expression of NLRP3 inflammasome and suppressed its activation. Baicalin significantly reduced the plaque area. Silencing NLRP3 resulted in decreased production of IL-1, IL-18, mitochondria ROS, total ROS, ICAM-1, and VCAM-1, and inhibition of NLRP3 inflammasome activation. CONCLUSION: Baicalin ameliorated atherosclerosis by inhibiting NLRP3 inflammasome.
Asunto(s)
Antiinflamatorios/farmacología , Aorta/efectos de los fármacos , Enfermedades de la Aorta/prevención & control , Aterosclerosis/prevención & control , Flavonoides/farmacología , Inflamasomas/antagonistas & inhibidores , Inflamación/prevención & control , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Animales , Antioxidantes/farmacología , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/patología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Modelos Animales de Enfermedad , Inflamasomas/genética , Inflamasomas/metabolismo , Inflamación/metabolismo , Inflamación/patología , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1/metabolismo , Interleucina-18/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
PURPOSE: To explore the effects of aspirin (ASP) on the proliferation and apoptosis of HepG2 hepatocellular carcinoma (HCC) cells via the Wnt/ß-catenin signaling pathway. METHODS: Human HCC cells were cultured and treated with ASP at different concentrations. Cell proliferation was determined with cell counting kit-8 (CCK-8) and colony formation, and the rate of apoptosis was measured by flow cytometry. Western blotting (WB) and quantitative polymerase chain reaction (qRT-PCR) assays were used to assess the changes in the expression levels of related proteins. RESULTS: ASP showed a time-and concentration-depented inhibitory effect on HepG2 cell proliferation. The number of colonies formed in ASP-treated HCC cells was significantly lower than in control cells. For HCC cells treated with ASP, the apoptosis rate enhanced with the increase of ASP concentration. The expression levels of TCF4 and LEF1, key molecules of the Wnt/ß-catenin signaling pathway, were lowered in HCC cells treated with 4 mM ASP, and the nuclear translocation of ß-catenin was weakened. The ß-catenin activator exerted a negative influence on the anticancer effect of ASP. CONCLUSIONS: ASP inhibits the proliferation and promotes the apoptosis of HCC cells through the Wnt/ß-catenin signaling pathway.
