4-Hydroxyphenylacetic acid is a phenolic acid with anti-inflammatory and anti-steatotic activities.1,2 It is formed via microbial metabolism of aromatic amino acids and polyphenolic compounds, including flavonoid glycosides, by gut microbiota.3,4,5 4-Hydroxyphenylacetic acid (100 mg/kg) inhibits seawater instillation-induced increases in TNF-α, IL-1β, and IL-6 levels in lung tissue and white blood cell numbers in bronchoalveolar lavage fluid (BALF) and prevents lung edema in a rat model of acute lung injury.1 It reverses hepatic steatosis in a mouse model of high-fat diet-induced obesity when administered via a subcutaneous implant at a dose of 350 ?g/day for two weeks.2 Levels of 4-hydroxyphenylacetic acid are increased and decreased in serum and urine, respectively, in rats fed a high-fat diet.3 Serum levels of 4-hydroxyphenylacetic acid are increased in patients with stage III pancreatic cancer.6
1.Liu, Z., Xi, R., Zhang, Z., et al.4-hydroxyphenylacetic acid attenuated inflammation and edema via suppressing HIF-1α in seawater aspiration-induced lung injury in ratsInt. J. Mol. Sci.15(7)12861-12884(2014) 2.Osborn, L.J., Schultz, K., Massey, W., et al.A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosisProc. Natl. Acad. Sci. USA119(48)e2202934119(2022) 3.Zeng, Y., Lin, Y., Li, L., et al.Targeted metabolomics for the quantitative measurement of 9 gut microbiota-host co-metabolites in rat serum, urine and feces by liquid chromatography-tandem mass spectrometryJ. Chromatogr. B. Analyt. Technol. Biomed. Life Sci.1110-1111133-143(2019) 4.Kim, D.-H., Jung, E.-A., Sohng, I.-S., et al.Intestinal bacterial metabolism of flavonoids and its relation to some biological activitiesArch. Pharm. Res.21(1)17-23(1998) 5.Chen, H., and Sang, S.Biotransformation of tea polyphenols by gut microbiotaJ. Funct. Foods726-42(2014) 6.Nishiumi, S., Shinohara, M., Ikeda, A., et al.Serum metabolomics as a novel diagnostic approach for pancreatic cancerMetabolomics6(4)518–528(2010)