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Punicalagin, a Pomegranate-Derived Ellagitannin, Suppresses Obesity and Obesity-Induced Inflammatory Responses Via the Nrf2/Keap1 Signaling Pathway

Authors
Kang, BobinKim, Chae YoungHwang, JisuJo, KyungaeKim, SingeunSuh, Hyung JooChoi, Hyeon-Son
Issue Date
11월-2019
Publisher
WILEY
Keywords
co-culture; HFD-fed mice; Nrf2; Keap1 signaling; obesity; obesity-induced inflammatory response; punicalagin
Citation
MOLECULAR NUTRITION & FOOD RESEARCH, v.63, no.22
Indexed
SCIE
SCOPUS
Journal Title
MOLECULAR NUTRITION & FOOD RESEARCH
Volume
63
Number
22
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/62011
DOI
10.1002/mnfr.201900574
ISSN
1613-4125
Abstract
Scope Punicalagin (PCG) is one of the most abundant phytochemicals found in pomegranates. The effects and mechanistic action of PCG on obesity and obesity-induced inflammatory and oxidant responses are investigated in vitro and in vivo. Methods and results The effect of PCG on adipogenesis is examined using Oil red O staining. The effects and mechanism of action of PCG on inflammatory responses are determined in adipocyte-conditioned medium (ACM)-cultured macrophages, a cell-to-cell contact system, and a transwell system. The effects of PCG on obesity and obesity-induced inflammatory/oxidant responses are examined in high-fat diet (HFD)-fed mice. PCG effectively suppresses lipid accumulation in adipocytes and adipocyte-induced inflammatory responses in adipocyte-macrophage co-culture systems. Small interfering RNA (siRNA) transfection indicates that the PCG-mediated anti-inflammatory effect is exerted via the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1(Nrf2/Keap1) pathway. PCG administration results in a significant reduction in body and white adipose tissue (WAT) weights. PCG favorably regulates pro- and anti-inflammatory cytokines, downregulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B). Immunohistochemical (IHC) analysis demonstrates that PCG differentially modulates the distribution of complement component 3 receptor 4 subunit (CD11c) and cluster of differentiation 206 (CD206). PCG regulates the level of antioxidant and oxidant molecules by activating Nrf2/Keap1 signaling. Conclusions PCG ameliorates obesity and obesity-induced inflammatory responses via activation of Nrf2/Keap1 signaling, suggesting that PCG has potential as an oral agent to control obesity-mediated diseases.
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보건과학대학 (바이오시스템의과학부)
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