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, 8β-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-α, 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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Inflammatory Agents / pharmacology*
-
Cell Line
-
Cyclooxygenase 2 / immunology
-
Cyclooxygenase 2 / metabolism
-
Dinoprostone / immunology
-
Dinoprostone / metabolism
-
Diterpenes / chemistry
-
Diterpenes / pharmacology*
-
Dose-Response Relationship, Drug
-
Interleukin-6 / immunology
-
Interleukin-6 / metabolism
-
Lipopolysaccharides / toxicity
-
MAP Kinase Kinase Kinase 5 / immunology*
-
MAP Kinase Kinase Kinase 5 / metabolism
-
MAP Kinase Signaling System / drug effects*
-
MAP Kinase Signaling System / immunology
-
Macrophages
-
Mice
-
Nitric Oxide / immunology
-
Nitric Oxide / metabolism
-
Nitric Oxide Synthase Type II / immunology
-
Nitric Oxide Synthase Type II / metabolism
-
RNA, Messenger / immunology
-
RNA, Messenger / metabolism
-
Reactive Oxygen Species / immunology*
-
Reactive Oxygen Species / metabolism
-
Sciuridae
-
TNF Receptor-Associated Factor 6 / immunology*
-
TNF Receptor-Associated Factor 6 / metabolism
-
Tumor Necrosis Factor-alpha / immunology
-
Tumor Necrosis Factor-alpha / metabolism
-
p38 Mitogen-Activated Protein Kinases / immunology*
-
p38 Mitogen-Activated Protein Kinases / metabolism
Substances
-
8-hydroxy-3-oxopimar-15-ene
-
Anti-Inflammatory Agents
-
Diterpenes
-
Interleukin-6
-
Lipopolysaccharides
-
RNA, Messenger
-
Reactive Oxygen Species
-
TNF Receptor-Associated Factor 6
-
Tumor Necrosis Factor-alpha
-
Nitric Oxide
-
Nitric Oxide Synthase Type II
-
Nos2 protein, mouse
-
Ptgs2 protein, mouse
-
Cyclooxygenase 2
-
p38 Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase Kinase 5
-
Map3k5 protein, mouse
-
Dinoprostone