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7336600 
Journal Article 
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 
Yan, J; Li, M; Wang, XD; Lu, ZY; Ni, XL 
2018 
Yes 
Biomedicine & Pharmacotherapy
ISSN: 0753-3322
EISSN: 1950-6007 
Elsevier Masson SAS 
105 
862-869 
English 
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. © 2018 
Atherosclerosis; Inflammation; IκBα/NF-κB; NLRP3-ASC; Peperomin E (PepE); acetylcysteine; antiinflammatory agent; apolipoprotein E; cryopyrin; herbaceous agent; inflammasome; interleukin 18; interleukin 1beta; interleukin 1beta converting enzyme; interleukin 6; monocyte chemotactic protein 1; monocyte chemotactic protein 2; oxidized low density lipoprotein; peperomin e; reactive oxygen metabolite; small interfering RNA; tumor necrosis factor; unclassified drug; 1,3 benzodioxole derivative; apolipoprotein E; cryopyrin; Nlrp3 protein, mouse; peperomin E; reactive oxygen metabolite; animal experiment; animal model; animal tissue; aortic endothelial cell; apoptosis; Article; cell infiltration; cell viability; comparative study; controlled study; disease course; down regulation; experimental atherosclerosis; heart protection; human; human cell; immunofluorescence; in vitro study; lipid diet; male; mouse; MTT assay; nonhuman; priority journal; reverse transcription polymerase chain reaction; RNA extraction; RNA isolation; signal transduction; triacylglycerol level; TUNEL assay; Western blotting; animal; antagonists and inhibitors; atherosclerosis; C57BL mouse; cell survival; deficiency; drug effect; inflammation; knockout mouse; lipid diet; metabolism; physiology; signal transduction; Animals; Apolipoproteins E; Atherosclerosis; Benzodioxoles; Cell Survival; Diet, High-Fat; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Reactive Oxygen Species; Signal Transduction