8 beta-hydroxy-3-oxopimar-15-ene exerts anti-inflammatory effects by inhibiting ROS-mediated activation of the TRAF6-ASK1-p38 signaling pathway

Authors
Cho, Jae-HeungLee, Jong HyunLee, Eun-JungNam, DongwooShim, Bum SangSong, Mi-YeonKim, Sung-SooKim, Sung-HoonJung, Sang HoonChung, Won-SeokAhn, Kwang Seok
Issue Date
2013-10
Publisher
INFORMA HEALTHCARE
Citation
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY, v.35, no.5, pp.549 - 557
Abstract
The flying squirrel's droppings (Pteropus pselaphon) have been used for improving the blood circulation, arresting bleeding to treat hematological disorders, and reducing pain. Here, 8 beta-hydroxy-3-oxopimar-15-ene (OXO), one of main constituents of P. pselaphon, was examined for its anti-inflammatory activity in murine macrophages. We found that OXO significantly suppressed LPS-induced nitric oxide (NO) without exerting cytotoxic effects on RAW 264.7 cells. OXO inhibited the expression of LPS-induced iNOS and COX-2 protein and their mRNA in a dose-dependent manner. Also, TNF-alpha, IL-6, and PGE2 secretion was decreased by OXO in LPS-stimulated macrophages. These inflammatory biomarkers were attributed to the suppression of LPS-induced activation of p38 MAPK and subsequent activation of two components of AP-1 (c-Jun and c-Fos), but not of ERK, JNK, NF-kappa B. Moreover, OXO inhibited LPS-induced intracellular reactive oxygen species (ROS) production and co-incubation of OXO and hydrogen peroxide (H2O2) suppressed the phosphorylation of p38 in a concentration-dependent manner. In addition, OXO completely disrupted the formation of TRAF6-ASK complex in the cells. Therefore, we demonstrate here that OXO can potentially inhibit several biomarkers related to inflammation through inhibition of ROS-mediated activation of TRAF6-ASK1-p38 pathway.
Keywords
NF-KAPPA-B; OXIDE SYNTHASE EXPRESSION; PROTEIN-KINASE PATHWAY; TOLL-LIKE RECEPTORS; INNATE IMMUNITY; TRANSCRIPTION FACTOR; GENE-EXPRESSION; P38 MAPK; INFLAMMATION; SUPPRESSION; NF-KAPPA-B; OXIDE SYNTHASE EXPRESSION; PROTEIN-KINASE PATHWAY; TOLL-LIKE RECEPTORS; INNATE IMMUNITY; TRANSCRIPTION FACTOR; GENE-EXPRESSION; P38 MAPK; INFLAMMATION; SUPPRESSION; 8 beta-hydroxy-3-oxopimar-15-ene; COX-2; inflammation; NO; TRAF6-ASK1-p38
ISSN
0892-3973
URI
https://pubs.kist.re.kr/handle/201004/127578
DOI
10.3109/08923973.2013.820742
Appears in Collections:
KIST Article > 2013
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE