Peperomin E (PepE) protects against high fat diet-induced atherosclerosis in Apolipoprotein E deficient (ApoE−/−) mice through reducing inflammation via the suppression of NLRP3 signaling pathway - 11/07/18
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Abstract |
Peperomin E (PepE) is a type of secolignan, a major component of the plant Peperomia dindygulensis. It has been shown to exert anti-inflammatory effects; however, the effects of PepE on human atherosclerosis remain unexplored. In the study, we investigated the role of PepE in high fat diet (HFD) induced atherosclerosis using apolipoprotein E defcient (ApoE−/−) mice. Elevated serum homocyteine, cholesterol, and triglyceride levels, accelerated progression of atherosclerosis and exacerbated macrophage infiltration into atherosclerotic lesions were observed in HFD-fed ApoE−/− mice, which were attenuated by PepE treatment. ApoE−/− mice fed with HFD exhibited significantly high levels of inflammation-associated regulators in artery tissues, accompanied with an increased expression of p-inhibitor of κBα (IκBα) and p-nuclear factor-kappa B (NF-κB), and the process was blocked by PepE administration. Further, we found NOD-like receptor pyrin 3 (NLRP3) inflammasome activation in artery tissues of HFD-fed ApoE−/− mice. In vitro, silencing NLRP3 using small interfering RNA efficiently inhibited oxidized-low-density lipoprotein (oxLDL)-induced ASC and Caspase-1 expressions, interleukin (IL)-1β and IL-18 production in human aortic endothelial cells (HAECs). Further experiments indicated that NLRP3-ASC pathway was activated by reactive oxygen species (ROS), since ROS scavenger of N-acetyl-cysteine (NAC) prevented, which was further reduced by PepE addition. However, the anti-inflammatory effects of PepE on oxLDL-incubated HAECs were abolished by over-expression NLRP3. Together, our study revealed that PepE inhibited atherosclerosis development in HFD-fed ApoE−/− mice by suppressing NLRP3 inflammatory signaling pathway, and suggested that PepE might be a potential therapeutic strategy in the prevention of atherosclerosis.
Le texte complet de cet article est disponible en PDF.Keywords : Atherosclerosis, Peperomin E (PepE), Inflammation, IκBα/NF-κB, NLRP3-ASC
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Vol 105
P. 862-869 - septembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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