PMID- 28415686
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 19
DP  - 2017 May 9
TI  - Chikusetsu saponin IVa ameliorates high fat diet-induced inflammation in adipose 
      tissue of mice through inhibition of NLRP3 inflammasome activation and NF-kappaB 
      signaling.
PG  - 31023-31040
LID - 10.18632/oncotarget.16052 [doi]
AB  - 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-1beta 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-kappaB signaling in vivo and LPS-induced NF-kappaB activation as reflected 
      by the fact that their phosphorylated forms and the ratios of pNF-kappaB/NF-kappaB, 
      pIKK/IKK, and pIkappaB/IkappaB 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-kappaB signaling. Thus, 
      CS can serve as a potential therapeutic drug in the prevention and treatment of 
      inflammation-associated diseases.
FAU - Yuan, Chengfu
AU  - Yuan C
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - Liu, Chaoqi
AU  - Liu C
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - Wang, Ting
AU  - Wang T
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - He, Yumin
AU  - He Y
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - Zhou, Zhiyong
AU  - Zhou Z
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - Dun, Yaoyan
AU  - Dun Y
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - Zhao, Haixia
AU  - Zhao H
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - Ren, Dongming
AU  - Ren D
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - Wang, Junjie
AU  - Wang J
AD  - Renhe Hospital of China Three Gorges University, Yichang, HuBei 443002, China.
FAU - Zhang, Changcheng
AU  - Zhang C
AD  - College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, 
      China.
FAU - Yuan, Ding
AU  - Yuan D
AD  - Renhe Hospital of China Three Gorges University, Yichang, HuBei 443002, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Saponins)
RN  - 51415-02-2 (chikusetsu saponin IVa)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Adipose Tissue/drug effects/metabolism/pathology
MH  - Animals
MH  - Diet, High-Fat/*adverse effects
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects
MH  - Homeostasis/drug effects
MH  - Inflammasomes/*metabolism
MH  - Lipid Metabolism/drug effects
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/drug effects/immunology/metabolism/pathology
MH  - Male
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Oleanolic Acid/*analogs & derivatives/pharmacology
MH  - Panniculitis/drug therapy/*etiology/*metabolism/pathology
MH  - Saponins/*pharmacology
MH  - Signal Transduction/*drug effects
PMC - PMC5458186
OTO - NOTNLM
OT  - ASC pyroptosome
OT  - Chikusetsu saponin IVa
OT  - NF-kappaB signaling
OT  - NLRP3 inflammasome
OT  - adipose tissue inflammation
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2017/04/19 06:00
MHDA- 2018/03/27 06:00
PMCR- 2017/05/09
CRDT- 2017/04/19 06:00
PHST- 2017/01/23 00:00 [received]
PHST- 2017/03/02 00:00 [accepted]
PHST- 2017/04/19 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/04/19 06:00 [entrez]
PHST- 2017/05/09 00:00 [pmc-release]
AID - 16052 [pii]
AID - 10.18632/oncotarget.16052 [doi]
PST - ppublish
SO  - Oncotarget. 2017 May 9;8(19):31023-31040. doi: 10.18632/oncotarget.16052.