8β-hydroxy-3-oxopimar-15-ene exerts anti-inflammatory effects by inhibiting ROS-mediated activation of the TRAF6-ASK1-p38 signaling pathway
- 8β-hydroxy-3-oxopimar-15-ene exerts anti-inflammatory effects by inhibiting ROS-mediated activation of the TRAF6-ASK1-p38 signaling pathway
- 조재흥; 이종현; 이은정; 남동우; 심범상; 송미연; 김성수; 김성훈; 정상훈; 정원석; 안광석
- 8β-hydroxy-3-oxopimar-15-ene; COX-2; inflammation; NO; TRAF6-ASK1-p38
- Issue Date
- Immunopharmacology and immunotoxicology
- VOL 35, NO 5, 549-557
- 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,
8b-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-a, 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-κB. 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.
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