Oncotarget

Research Papers:

Chikusetsu saponin IVa ameliorates high fat diet-induced inflammation in adipose tissue of mice through inhibition of NLRP3 inflammasome activation and NF-κB signaling

Chengfu Yuan _, Chaoqi Liu, Ting Wang, Yumin He, Zhiyong Zhou, Yaoyan Dun, Haixia Zhao, Dongming Ren, Junjie Wang, Changcheng Zhang and Ding Yuan

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Oncotarget. 2017; 8:31023-31040. https://doi.org/10.18632/oncotarget.16052

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Abstract

Chengfu Yuan1, Chaoqi Liu1, Ting Wang1, Yumin He1, Zhiyong Zhou1, Yaoyan Dun1, Haixia Zhao1, Dongming Ren1, Junjie Wang2, Changcheng Zhang1, Ding Yuan2

1College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China

2Renhe Hospital of China Three Gorges University, Yichang, HuBei 443002, China

Correspondence to:

Chengfu Yuan, email: yuancf46@ctgu.edu.cn

Changcheng Zhang, email: greatwall1@ctgu.edu.cn

Ding Yuan, email: yuancf46@163.com

Junjie Wang, email: junjiewang@ctgu.edu.cn

Keywords: chikusetsu saponin IVa, adipose tissue inflammation, NLRP3 inflammasome, NF-κB signaling, ASC pyroptosome

Received: January 23, 2017     Accepted: March 02, 2017     Published: March 09, 2017

ABSTRACT

Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice. Moreover, CS treatment also inhibited the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs). Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed HFD-induced NF-κB signaling in vivo and LPS-induced NF-κB activation as reflected by the fact that their phosphorylated forms and the ratios of pNF-κB/NF-κB, pIKK/IKK, and pIκB/IκB were all decreased in EAT from HFD-fed mice treated with CS as compared with those of HFD mice. Taking together, this study has revealed that CS effectively inhibits HFD-induced inflammation in adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and NF-κB signaling. Thus, CS can serve as a potential therapeutic drug in the prevention and treatment of inflammation-associated diseases.


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