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

Publication date: September 2018Source: Biomedicine & Pharmacotherapy, Volume 105Author(s): Jin Yan, Ming Li, Xiao-Dong Wang, Zi-Ying Lu, Xiao-Long NiAbstractPeperomin 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 wa...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research