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4-hydroxyphenylacetic acid, a major microbiota-derived metabolite of polyphenols, is involved in the antioxidative action. 4-hydroxyphenylacetic acid induces expression of Nrf2[1].

4-Hydroxyphenylacetic acid (6, 12, or 25 mg/kg) increases Nrf2 translocation to the nucleus and enhances the activity of phase II and antioxidant enzymes. The protein levels of nuclear Nrf2 are increased by 170% and 230% in pre-treated 12 and 25 mg/kg 4-Hydroxyphenylacetic acid groups, respectively, compared with the control group.The 4-Hydroxyphenylacetic acid pretreatment at a final dose of 25 mg/kg markedly and selectively up-regulated the target genes of phase II enzymes and resulted in higher up-regulation than that of the control group by 270%, 400%, and 500% or UGT1A1, UGT1A9, and SULT2A1, respectively. 4-Hydroxyphenylacetic acid also suppresses the expression of CYP2E1[1].

[1]. Zhao H, et al. 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase IIand Antioxidant Enzymes in Mice. Front Pharmacol. 2018 Jun 19;9:653.

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