Parthenolide, a feverfew-derived phytochemical, ameliorates obesity and obesity-induced inflammatory responses via the Nrf2/Keap1 pathway
- Authors
- Kim, Chae Young; Kang, Bobin; Suh, Hyung Joo; Choi, Hyeon-Son
- Issue Date
- 7월-2019
- Publisher
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
- Keywords
- Parthenolide; Co-culture; Obesity; Obesity-induced inflammatory response; Nrf2/Keap1 signaling
- Citation
- PHARMACOLOGICAL RESEARCH, v.145
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHARMACOLOGICAL RESEARCH
- Volume
- 145
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/64261
- DOI
- 10.1016/j.phrs.2019.104259
- ISSN
- 1043-6618
- 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 down-regulating 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-kappa B 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Health Sciences > School of Biosystems and Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.