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Published on: August 28, 2009
bis-Eugenol Induces Heme Oxygenase 1 Expression and Activation of Nrf2 in RAW264.7 Cells
Yukio Murakami1, Akihiro Inoue2, Kaho Matsumura2
1Division of Oral Diagnosis and General Dentistry, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Japan ymura@dent.meikai.ac.jp.
Background/Aim:
Eugenol dimer (bis-eugenol), a representative ortho-bisphenol, has been reported to have potent antioxidant/anti-inflammatory activity. To clarify the antioxidant/anti-inflammatory mechanisms of bis-eugenol, we investigated its involvement in heme oxygenase-1 (HO-1) expression and anti-inflammatory activity.
Materials And Methods:
HO-1 expression in RAW264.7 cells was measured using real-time reverse transcription polymerase chain reaction analysis (RT-PCR) and western blot analysis. Expression of Escherichia coli lipopolysaccharide (LPS)-stimulated cyclooxygenase-2 (Cox2) and tumor necrosis factor-α (Tnfα) mRNA was measured using RT-PCR. Nuclear factor (NF)-erythroid 2-related factor 2 (Nrf2) activation was measured using an ELISA-based transcription factor assay.
Results:
bis-Eugenol induced HO-1 expression in a dose-dependent manner, and tin-protoporphyrin IX (PPIX) suppressed this increase in terms of Ho-1 mRNA. LPS-stimulated expression of Cox2 and Tnfα mRNA was significantly suppressed by bis-eugenol, but not by eugenol. The inhibitory effect of bis-eugenol on LPS-stimulated Cox2 and Tnfα mRNA expression was not changed by the addition of PPIX, but an inhibitory effect was evident in the case of eugenol. bis-Eugenol activated Nrf2 and promoted its binding to the antioxidant response element (ARE).
Conclusion:
bis-Eugenol is a potent HO-1 inducer and Nrf2 activator. The present findings offer interesting insights for re-evaluating the antioxidant/anti-inflammatory mechanisms of ortho-bisphenols.
