Anti-inflammatory activity of lipophilic epigallocatechin gallate (EGCG) derivatives in LPS-stimulated murine macrophages

Abstract

Epigallocatechin gallate (EGCG), the major polyphenol in green tea and the main bioactive compound responsible for the health benefits of tea consumption, has been proposed as a functional ingredient for food and natural health products. However, EGCG is hydrophilic with poor cellular absorption and thus compromised bioefficiency in vivo. In order to enhance the lipophilicity of EGCG for improved bioefficiency and to take advantage of the health beneficial omega 3 fatty acids, the EGCG molecule was esterified with docosapentaenoic acid (DPA), upon which a mixture of ester derivatives with different degrees of substitution was produced. The EGCG-DPA esters were evaluated for their anti-inflammatory activity in LPS (lipopolysaccharides)-stimulated murine RAW 264.7 macrophages. The production of pro-inflammatory mediators nitric oxide (NO) and prostaglandin (PGE(2)) was significantly inhibited by treatment of EGCG-DPA esters, and the inhibition was largely due to their down-regulatory effect on iNOS (inducible NO synthase) and COX (cyclooxygenase)-2 gene expression at transcriptional level. The EGCG-DPA esters effectively suppressed the expression of iNOS and COX -2 proteins as well as their mRNA, as observed with western blotting and RT-PCR analyses. Ester derivatives of EGCG with other fatty acids (stearic acid, SA; eicosapentaenoic acid, EPA; and docosahexaenoic acid, DHA) were also prepared in the form of pure tetraesters, which also exhibited anti-inflammatory effect in the macrophages. The results suggest that EGCG ester derivatives with anti-inflammatory potentials may be useful in preventing/treating inflammation-mediated diseases and health conditions.