Cho, Jae-Heung Lee, Jong Hyun Lee, Eun-Jung Nam, Dongwoo Shim, Bum Sang Song, Mi-Yeon Kim, Sung-Soo Kim, Sung-Hoon Jung, Sang Hoon Chung, Won-Seok Ahn, Kwang Seok 2024-01-20T11:30:58Z 2024-01-20T11:30:58Z 2021-09-05 2013-10 0892-3973 https://pubs.kist.re.kr/handle/201004/127578 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. English INFORMA HEALTHCARE 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 exerts anti-inflammatory effects by inhibiting ROS-mediated activation of the TRAF6-ASK1-p38 signaling pathway Article 10.3109/08923973.2013.820742 1 IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY, v.35, no.5, pp.549 - 557 IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY 35 5 549 557 scie scopus 000324768800003 2-s2.0-84884641728 Immunology Pharmacology & Pharmacy Toxicology Immunology Pharmacology & Pharmacy Toxicology Article 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