Andrographolide induces the COX‐2 expression in MC3T3 – E1 cells via the ERK1/2 pathway

Andrographolide is a labdane diterpene that possess antiinflamatory properties. This drug reduces iNOS, IL‐8 and COX‐2 expression in macrophages and neutrophils interfering with NF‐κB binding. COX‐2 are involved in the prostaglandins synthesis during inflammatory process, and selective COX‐2 inhibitors have been useful for rheumatoid arthritis and osteoarthritis treatment; however it is widely recognized that COX‐2 inhibition can also interfere with the bone repair, affecting the fracture healing. In this work we assess if androgrpholide can interfere with the COX‐2 expression induced by TNF‐α (proinflammatory cytokine) or TGF‐β (bone growth factor) in MC3T3 – E1 murine preosteoblastic cells. We analyzed the ERK1/2 and SMAD 2–3 phosphorylation and COX‐2 expression by western blot. By Q‐RT‐PCR we assess the effect of andrographolide on COX‐2, cbfa1 and NF‐κB mRNA level in cells treated with TNF‐α or TGF‐β. We demonstrated that andrographolide potentiates the COX‐2 expression and ERK1/2 phosphorylation induced by TNF‐α or TGF‐β in MC3T3 – E1 cells. Moreover we observed that andrographolide by itself was able to stimulate the ERK1/2 phosphorylation and COX‐2 expression in a dose dependant manner. We conclude that andrographolide can modulate directly the osteoblast activity inducing COX‐2 expression and potentiating other stimuli via ERK1/2 pathway. This work was supported by FONDEF D04I1240