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

Abstract

SCOPE\nPunicalagin (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 were investigated in vitro and in vivo.\n\n\nMETHODS AND RESULTS\nThe effect of PCG on adipogenesis was examined using Oil red O staining. The effects and mechanism of action of PCG on inflammatory responses were 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 were examined in high-fat diet (HFD)-fed mice. PCG effectively suppressed lipid accumulation in adipocytes and adipocyte-induced inflammatory responses in adipocyte-macrophage co-culture systems. siRNA transfection indicated that the PCG-mediated anti-inflammatory effect was exerted via the Nrf2/Keap1 pathway. PCG administration resulted in a significant reduction in body and white adipose tissue (WAT) weights. PCG favorably regulated pro- and anti-inflammatory cytokines, downregulating NF-κB. Immunohistochemical (IHC) analysis demonstrated that PCG differentially modulated the distribution of CD11c and CD206. PCG regulated the level of antioxidant and oxidant molecules by activating Nrf2/Keap1 signaling.\n\n\nCONCLUSIONS\nPCG ameliorated 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. This article is protected by copyright. All rights reserved.