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Food Chem Toxicol. 2018 Jan;111:176-188. doi: 10.1016/j.fct.2017.11.014. Epub 2017 Nov 9.

Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-κB and activation of nuclear factor erythroid 2-related factor 2.

Author information

1
College of Korean Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do 38610, Republic of Korea.
2
HaniBio Co., Ltd., Gyeongsan, Gyeongsangbuk-do 38540, Republic of Korea.
3
College of Korean Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do 38610, Republic of Korea. Electronic address: skek023@dhu.ac.kr.
4
College of Korean Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do 38610, Republic of Korea. Electronic address: sckim@dhu.ac.kr.

Abstract

Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H2O2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2.

KEYWORDS:

Anti-inflammation; D-galactosamine/lipopolysaccharide-induced liver injury; Hemistepsin A; Nuclear factor erythroid 2-related factor 2 (Nrf2); Nuclear factor-κB (NF-κB)

PMID:
29129664
DOI:
10.1016/j.fct.2017.11.014
[Indexed for MEDLINE]

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