Study On The Effect Of EGCG On LPS-induced P38 MAPK Signal Transduction

Epigallocatechin gallate (EGCG) is a predominant component of the green tea polyphenols. Recent studies show that EGCG have anti-inflammatory effects besides its anticancer and antioxidant properties. But the anti-inflammatory mechanisms are still little known. In the present study, we investigate the effect of EGCG on lipopolysacchande (LPS)-mediated inflammatory on the level of p38 MAPK pathway and inflammatory factors and study the potent anti-inflammatory mechanisms of EGCG through its intervene effect on animal acute lung injury (ALI) model.1. The direct effect of EGCG on LPS in vitro:We investigated the direct effect of EGCG on LPS through the transmission electron microscopy and limulus test for the first time. The results showed that EGCG had no significant effect on the structure and quantity of LPS. which indicated that EGCG had no direct effect on LPS.2. The effect of EGCG on LPS-induced mouse macrophages:LPS was used to stimulate mouse macrophage line RAW264.7. Western blotting was used to measure the phosphorylation of p38 MAPK , while ELISA was used to detect the expression of TNF-a and PGE2 . The findings indicated that EGCG could inhibit LPS-induced phosphorylation of p38 MAPK , TNF-a , and PGE2 production. The findings from immunocytochemistry on mouse peritoneal macrophages also showed the inhibition effect of EGCG on p38 MAPK pathway.3. The effect of EGCG on oleic acid-induced ALI mouse model:We use an oleic acid-induced ALI mouse model to investigate the effect of EGCG in vivo for the first time. EGCG is given before injection of oleic acid at doses of 6,12, and 25 mg/kg. The phosphorylation of p38 MAPK in the lung and production of serum TNF-a in mice were measured after injection of oleic acid. The findings showed that EGCG could inhibit the phosphorylation of p38 MAPK in the lung and reduce the serum TNF-a, which suggested that EGCG had a beneficial effect on ALI induced by oleic acid.In conclusion, our studies suggested that EGCG had no direct effect on LPS but blocked cellular signal pathway. The inhibition of EGCG on UPS-induced TNF-a production was mediated at least in part through blocking of p38 MAPK pathway. In addition, EGCG had a beneficial effect on acute lung injury induced by oleic acid in mice. The inhibition of phosphated p38 MAPK and the ultimate reduction of TNF-a in serum may be involved in its mechanism.