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

Bobin Kang, Chae Young Kim, Jisu Hwang, Kyungae Jo, Singeun Kim, Hyung Joo Suh, Hyeon Son Choi

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

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-κB). 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.

Original languageEnglish
Article number1900574
JournalMolecular Nutrition and Food Research
Volume63
Issue number22
DOIs
Publication statusPublished - 2019 Nov 1

Bibliographical note

Funding Information:
B.K. performed major experiments and analyzed data; C.Y.K., J.H., K.J., and S.K. participated in experiments, and interpreted and analyzed data; H.J.S. analyzed and interpreted data; and H.‐S.C. designed experiments, analyzed, and interpreted data, and wrote the paper, with final approval of the version to be submitted. This work was supported by the National Research Foundation of Korea, a grant funded by the Korean government (the Ministry of Education) (NRF2015R1D1A1A01059729) (2018).

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • HFD-fed mice
  • Nrf2/Keap1 signaling
  • co-culture
  • obesity
  • obesity-induced inflammatory response
  • punicalagin

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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