Brassinin, a phytoalexin in cruciferous vegetables, suppresses obesity-induced inflammatory responses through the Nrf2-HO-1 signaling pathway in an adipocyte-macrophage co-culture system

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

Research output: Contribution to journalArticle

Abstract

The aim of this study was to investigate the effect of brassinin (BR), a phytoalexin found in plants belonging to the Brassicaceae family, on the obesity-induced inflammatory response and its molecular mechanism in co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages. BR effectively suppressed lipid accumulation by down-regulating the expression of adipogenic factors, which in turn, were regulated by early adipogenic factors such as CCAAT-enhancer-binding protein-β and Kruppel-like factor 2. Production of inflammatory cytokines and reactive oxygen species, induced by adipocyte-conditioned medium, was significantly decreased in BR-treated cells. This effect of BR was more prominent in contact co-culture of adipocytes and macrophages with a 90% and 34% reduction in IL-6 and MCP-1 levels, respectively. BR also restored adiponectin expression, which was significantly reduced by culturing adipocytes in macrophage-conditioned medium. In the transwell system, BR increased the protein levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target molecule, hemoxygenase-1 (HO-1), by 55%–93% and 45%–48%, respectively, and also increased Nrf2 translocation into the nucleus. However, knockdown of Nrf2 or HO-1 in RAW264.7 cells restored this BR-mediated inhibition of IL-6 and MCP-1 production. These results indicated that BR inhibited obesity-induced inflammation via the Nrf2-HO-1 pathway.

Original languageEnglish
JournalPhytotherapy Research
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Coculture Techniques
Adipocytes
Vegetables
Obesity
Macrophages
Conditioned Culture Medium
Interleukin-6
NF-E2-Related Factor 2
Kruppel-Like Transcription Factors
CCAAT-Enhancer-Binding Proteins
Brassicaceae
brassinin
phytoalexins
Adiponectin
Reactive Oxygen Species
Cytokines
Inflammation
Lipids

Keywords

  • brassinin
  • co-culture
  • nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling pathway
  • obesity-induced inflammation

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{8d1c150c29f345b5b74151a4fa3854e7,
title = "Brassinin, a phytoalexin in cruciferous vegetables, suppresses obesity-induced inflammatory responses through the Nrf2-HO-1 signaling pathway in an adipocyte-macrophage co-culture system",
abstract = "The aim of this study was to investigate the effect of brassinin (BR), a phytoalexin found in plants belonging to the Brassicaceae family, on the obesity-induced inflammatory response and its molecular mechanism in co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages. BR effectively suppressed lipid accumulation by down-regulating the expression of adipogenic factors, which in turn, were regulated by early adipogenic factors such as CCAAT-enhancer-binding protein-β and Kruppel-like factor 2. Production of inflammatory cytokines and reactive oxygen species, induced by adipocyte-conditioned medium, was significantly decreased in BR-treated cells. This effect of BR was more prominent in contact co-culture of adipocytes and macrophages with a 90{\%} and 34{\%} reduction in IL-6 and MCP-1 levels, respectively. BR also restored adiponectin expression, which was significantly reduced by culturing adipocytes in macrophage-conditioned medium. In the transwell system, BR increased the protein levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target molecule, hemoxygenase-1 (HO-1), by 55{\%}–93{\%} and 45{\%}–48{\%}, respectively, and also increased Nrf2 translocation into the nucleus. However, knockdown of Nrf2 or HO-1 in RAW264.7 cells restored this BR-mediated inhibition of IL-6 and MCP-1 production. These results indicated that BR inhibited obesity-induced inflammation via the Nrf2-HO-1 pathway.",
keywords = "brassinin, co-culture, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling pathway, obesity-induced inflammation",
author = "Bobin Kang and Kim, {Chae Young} and Jisu Hwang and Suh, {Hyung Joo} and Choi, {Hyeon Son}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/ptr.6333",
language = "English",
journal = "Phytotherapy Research",
issn = "0951-418X",
publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - Brassinin, a phytoalexin in cruciferous vegetables, suppresses obesity-induced inflammatory responses through the Nrf2-HO-1 signaling pathway in an adipocyte-macrophage co-culture system

AU - Kang, Bobin

AU - Kim, Chae Young

AU - Hwang, Jisu

AU - Suh, Hyung Joo

AU - Choi, Hyeon Son

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The aim of this study was to investigate the effect of brassinin (BR), a phytoalexin found in plants belonging to the Brassicaceae family, on the obesity-induced inflammatory response and its molecular mechanism in co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages. BR effectively suppressed lipid accumulation by down-regulating the expression of adipogenic factors, which in turn, were regulated by early adipogenic factors such as CCAAT-enhancer-binding protein-β and Kruppel-like factor 2. Production of inflammatory cytokines and reactive oxygen species, induced by adipocyte-conditioned medium, was significantly decreased in BR-treated cells. This effect of BR was more prominent in contact co-culture of adipocytes and macrophages with a 90% and 34% reduction in IL-6 and MCP-1 levels, respectively. BR also restored adiponectin expression, which was significantly reduced by culturing adipocytes in macrophage-conditioned medium. In the transwell system, BR increased the protein levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target molecule, hemoxygenase-1 (HO-1), by 55%–93% and 45%–48%, respectively, and also increased Nrf2 translocation into the nucleus. However, knockdown of Nrf2 or HO-1 in RAW264.7 cells restored this BR-mediated inhibition of IL-6 and MCP-1 production. These results indicated that BR inhibited obesity-induced inflammation via the Nrf2-HO-1 pathway.

AB - The aim of this study was to investigate the effect of brassinin (BR), a phytoalexin found in plants belonging to the Brassicaceae family, on the obesity-induced inflammatory response and its molecular mechanism in co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages. BR effectively suppressed lipid accumulation by down-regulating the expression of adipogenic factors, which in turn, were regulated by early adipogenic factors such as CCAAT-enhancer-binding protein-β and Kruppel-like factor 2. Production of inflammatory cytokines and reactive oxygen species, induced by adipocyte-conditioned medium, was significantly decreased in BR-treated cells. This effect of BR was more prominent in contact co-culture of adipocytes and macrophages with a 90% and 34% reduction in IL-6 and MCP-1 levels, respectively. BR also restored adiponectin expression, which was significantly reduced by culturing adipocytes in macrophage-conditioned medium. In the transwell system, BR increased the protein levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target molecule, hemoxygenase-1 (HO-1), by 55%–93% and 45%–48%, respectively, and also increased Nrf2 translocation into the nucleus. However, knockdown of Nrf2 or HO-1 in RAW264.7 cells restored this BR-mediated inhibition of IL-6 and MCP-1 production. These results indicated that BR inhibited obesity-induced inflammation via the Nrf2-HO-1 pathway.

KW - brassinin

KW - co-culture

KW - nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling pathway

KW - obesity-induced inflammation

UR - http://www.scopus.com/inward/record.url?scp=85062784153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062784153&partnerID=8YFLogxK

U2 - 10.1002/ptr.6333

DO - 10.1002/ptr.6333

M3 - Article

C2 - 30848529

AN - SCOPUS:85062784153

JO - Phytotherapy Research

JF - Phytotherapy Research

SN - 0951-418X

ER -