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 journalArticle

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
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Punicaceae
obesity
Obesity
inflammation
adipocytes
oxidants
proteins
Adipocytes
macrophages
Oxidants
pomegranates
white adipose tissue
coculture
transfection
high fat diet
tissue weight
small interfering RNA
Kelch-Like ECH-Associated Protein 1
punicalagin
ellagitannin

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

Punicalagin, a Pomegranate-Derived Ellagitannin, Suppresses Obesity and Obesity-Induced Inflammatory Responses Via the Nrf2/Keap1 Signaling Pathway. / Kang, Bobin; Kim, Chae Young; Hwang, Jisu; Jo, Kyungae; Kim, Singeun; Suh, Hyung Joo; Choi, Hyeon Son.

In: Molecular Nutrition and Food Research, 01.01.2019.

Research output: Contribution to journalArticle

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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.",
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author = "Bobin Kang and Kim, {Chae Young} and Jisu Hwang and Kyungae Jo and Singeun Kim and Suh, {Hyung Joo} and Choi, {Hyeon Son}",
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T1 - Punicalagin, a Pomegranate-Derived Ellagitannin, Suppresses Obesity and Obesity-Induced Inflammatory Responses Via the Nrf2/Keap1 Signaling Pathway

AU - Kang, Bobin

AU - Kim, Chae Young

AU - Hwang, Jisu

AU - Jo, Kyungae

AU - Kim, Singeun

AU - Suh, Hyung Joo

AU - Choi, Hyeon Son

PY - 2019/1/1

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N2 - 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.

AB - 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.

KW - co-culture

KW - HFD-fed mice

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KW - obesity-induced inflammatory response

KW - punicalagin

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