Gambogic acid protects from endotoxin shock by suppressing pro-inflammatory factors in vivo and in vitro.
OBJECTIVE
Gambogic acid (GBA) targeted Heat shock protein 90 (Hsp90) and prohibited TNF-α/NF-κB signaling pathway. It can be inferred that the anti-inflammatory activity of GBA results from inhibiting the cytokine production via NF-κB signaling pathway. We used the RAW264.7 cell line and the endotoxin shock mouse model to confirm the hypothesis that GBA protects mice from endotoxin shock by suppressing cytokine synthesis.


METHODS
RAW264.7 cells were cultured and the endotoxin shocked mice model was constructed. ELISA was employed to evaluate the change of cytokine secretion levels. The effects of GBA on the activation of NF-κB signaling pathway were also determined by western blot and immune-fluorescent analysis. Cell viability was determined by MTT assay, and the cell migration was tested by wound healing assay.


RESULTS
Our results demonstrated that GBA significantly inhibited the LPS-induced release of pro-inflammatory factors both in cell lines and mice serum, thereby protecting mice from endotoxin shock. Furthermore, we observed that the reduction of inflammatory cytokines interleukin 1-beta, interleukin 6 and TNF-α resulted from the Hsp90's client protein IKK degradation and the suppression of NF-κB pathway. Moreover, GBA suppressed the migration of LPS-induced RAW264.7 cells.


CONCLUSIONS
Our results indicate that GBA has a potential both as an antitumor and anti-inflammatory therapeutic agent.
State Key Lab of Cellular Stress Biology, School of Life Sciences, Xiamen University, No. 422, South Si-ming Road, Xiamen 361005, China.
Jing
J
Geng
Shuyan
S
Xiao
Zhonghui
Z
Zheng
Siyang
S
Song
Lianru
L
Zhang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D051550:I-kappa B Kinase / Q000276:immunology; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology; D014945:Wound Healing; D044004:Xanthones / Q000494:pharmacology / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D044004:Xanthones; C052659:gambogic acid; D051550:I-kappa B Kinase