Parthenolide, a feverfew-derived phytochemical, ameliorates obesity and obesity-induced inflammatory responses via the Nrf2/Keap1 pathway

Chae Young Kim, Bobin Kang, Hyung Joo Suh, Hyeon Son Choi

Research output: Contribution to journalArticle

Abstract

Parthenolide (PL) is one of the most abundant sesquiterpene lactones found in the plant feverfew (Tanacetum parthenium (L.) Sch.Bip.). PL was investigated for its effect on obesity and obesity-induced inflammatory/oxidant responses in vitro and in vivo. An obesity-induced inflammatory response was induced in various co-culture systems using adipocytes (3T3-L1) and macrophages (RAW264.7) in vitro and the effect of PL and its mechanism of action were determined. PL effectively suppressed the adiposity-induced inflammatory responses by downregulating IL-6 (40–42%) and MCP-1 (26–37%) in 3T3-CM-cultured macrophages and contact co-culture system. PL also favorably regulated the dysregulations of adiponectin and resistin in macrophage-conditioned medium (RAW-CM)-cultured adipocytes. In transwell system of adipocyte and macrophage, PL was shown to upregulated Nrf2 and its target molecule, HO-1 by promoting nuclear translocation of Nrf2. In particular, in siRNA knockdown study, the PL-mediated anti-inflammatory response was exerted via the Nrf2/Keap1 pathway. In animal study using high-fat diet (HFD)-fed mice, PL-administered mice showed a significant reduction in body weight and white adipose tissues (WATs). This PL-mediated anti-obese effect was connected to anti-inflammatory responses with the regulation of inflammatory cytokines, and the downregulation of NF-κB and MAPKs. Furthermore, PL differentially modulated CD11c and CD206, which are pro-/anti-inflammatory phenotypes of ATMs, in stroma vascular fraction (SVF) and immunohistochemistry (IHC) staining analyses. PL also regulated the level of (anti)oxidant molecules with the activation of Nrf2/Keap1signaling. Taken together, PL inhibited obesity and obesity-induced inflammatory responses via the activation of Nrf2/Keap1 signaling, indicating a potential of PL as a functional agent to control obesity-related diseases.

Original languageEnglish
Article number104259
JournalPharmacological Research
Volume145
DOIs
Publication statusPublished - 2019 Jul 1

Fingerprint

Tanacetum parthenium
Phytochemicals
Obesity
Macrophages
Adipocytes
Anti-Inflammatory Agents
Coculture Techniques
Oxidants
parthenolide
Down-Regulation
Resistin
White Adipose Tissue
Sesquiterpenes
Adiponectin
Adiposity
High Fat Diet
Lactones

Keywords

  • Co-culture
  • Nrf2/Keap1 signaling
  • Obesity
  • Obesity-induced inflammatory response
  • Parthenolide

ASJC Scopus subject areas

  • Pharmacology

Cite this

Parthenolide, a feverfew-derived phytochemical, ameliorates obesity and obesity-induced inflammatory responses via the Nrf2/Keap1 pathway. / Kim, Chae Young; Kang, Bobin; Suh, Hyung Joo; Choi, Hyeon Son.

In: Pharmacological Research, Vol. 145, 104259, 01.07.2019.

Research output: Contribution to journalArticle

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abstract = "Parthenolide (PL) is one of the most abundant sesquiterpene lactones found in the plant feverfew (Tanacetum parthenium (L.) Sch.Bip.). PL was investigated for its effect on obesity and obesity-induced inflammatory/oxidant responses in vitro and in vivo. An obesity-induced inflammatory response was induced in various co-culture systems using adipocytes (3T3-L1) and macrophages (RAW264.7) in vitro and the effect of PL and its mechanism of action were determined. PL effectively suppressed the adiposity-induced inflammatory responses by downregulating IL-6 (40–42{\%}) and MCP-1 (26–37{\%}) in 3T3-CM-cultured macrophages and contact co-culture system. PL also favorably regulated the dysregulations of adiponectin and resistin in macrophage-conditioned medium (RAW-CM)-cultured adipocytes. In transwell system of adipocyte and macrophage, PL was shown to upregulated Nrf2 and its target molecule, HO-1 by promoting nuclear translocation of Nrf2. In particular, in siRNA knockdown study, the PL-mediated anti-inflammatory response was exerted via the Nrf2/Keap1 pathway. In animal study using high-fat diet (HFD)-fed mice, PL-administered mice showed a significant reduction in body weight and white adipose tissues (WATs). This PL-mediated anti-obese effect was connected to anti-inflammatory responses with the regulation of inflammatory cytokines, and the downregulation of NF-κB and MAPKs. Furthermore, PL differentially modulated CD11c and CD206, which are pro-/anti-inflammatory phenotypes of ATMs, in stroma vascular fraction (SVF) and immunohistochemistry (IHC) staining analyses. PL also regulated the level of (anti)oxidant molecules with the activation of Nrf2/Keap1signaling. Taken together, PL inhibited obesity and obesity-induced inflammatory responses via the activation of Nrf2/Keap1 signaling, indicating a potential of PL as a functional agent to control obesity-related diseases.",
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