Involvement of heme oxygenase-1 induction in inhibitory effect of ethyl gallate isolated from Galla Rhois on nitric oxide production in RAW 264.7 macrophages

In the present study, we investigated an anti-inflammatory effect of ethyl gallate (EG) isolated from Galla Rhois as evaluated by inhibition of nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression, and a potential role of heme oxygenase-1 (HO-1) in the inhibition of NO production elicited by EG. Treatment of RAW264.7 macrophages with EG significantly inhibited the production of NO and iNOS expression stimulated by lipopolysaccharide (LPS). We also demonstrated that EG treatment increased HO-1 mRNA and protein expression, as assessed by quantitative RT-PCR and Western blot analysis. EG treatment also increased the levels of nuclear factor-erythroid 2-related factor 2, which is critical for transcriptional induction of HO-1. In addition, treatment with SnPP (tin protoporphyrin IX), a selective HO-1 inhibitor, counteracted the inhibitory effect of EG on nitrite production, suggesting that HO-1 is, at least in part, implicated in the inhibition of NO production induced by EG treatment. Taken together, these results indicate that EG isolated from Galla Rhois suppresses NO production in LPS-stimulated RAW 264.7 macrophages via HO-1 induction.