biostudies-literatureNguyen QNNational Research Foundation of Korea3387https://www.ebi.ac.uk/biostudies/studies/S-EPMC9740217biostudies-literatureUnknown11(23)<i>Acer tegmentosum</i>, a deciduous tree belonging to Aceraceae, has been used in traditional oriental medicine for treating hepatic disorders, such as hepatitis, cirrhosis, and liver cancer. We evaluated the estrogen-like effects of <i>A. tegmentosum</i> using an estrogen receptor (ER)-positive breast cancer cell line, namely MCF-7, to identify potential phytoestrogens and found that an aqueous extract of <i>A. tegmentosum</i> promoted cell proliferation in MCF-7 cells. Five phenolic compounds (<b>1</b>-<b>5</b>) were separated and identified from the active fraction using bioassay-guided fractionation of crude <i>A. tegmentosum</i> extract and phytochemical analysis. The chemical structures of the compounds were characterized as vanillic acid (<b>1</b>), 4-hydroxy-benzoic acid (<b>2</b>), syringic acid (<b>3</b>), isoscopoletin (<b>4</b>), and (<i>E</i>)-ferulic acid (<b>5</b>) based on the analysis of their nuclear magnetic resonance spectra and liquid chromatography-mass spectrometry data. All five compounds were evaluated using an E-screen assay for their estrogen-like effects on MCF-7 cells. Among the tested compounds, only 4-hydroxy-benzoic acid (<b>2</b>) promoted the proliferation of MCF-7 cells, which was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of 4-hydroxy-benzoic acid (<b>2</b>) was evaluated via western blotting analysis to determine the expression levels of extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), serine/threonine kinase (AKT), and ERα. Our results demonstrated that 4-hydroxy-benzoic acid (<b>2</b>) induced the increase in the protein expression levels of p-ERK, p-AKT, p-PI3K, and p-Erα, concentration dependently. Collectively, these experimental results suggest that 4-hydroxy-benzoic acid (<b>2</b>) is responsible for the estrogen-like effects of <i>A. tegmentosum</i> and may potentially aid in the control of estrogenic effects during menopause.Plants (Basel, Switzerland)Estrogenic Activity of 4-Hydroxy-Benzoic Acid from <i>Acer tegmentosum</i> via Estrogen Receptor α-Dependent Signaling Pathways.PMC97402172019R1A5A20273402019R1A5A2027340 and 2021R1A2C2007937, 2020M3A9E4104380122021R1A2C20079372020M3A9E410438012Kim BPang CHong JHLee DEJang YSKim KHLee SRNguyen QNKang KSfalseEstrogenic Activity of 4-Hydroxy-Benzoic Acid from <i>Acer tegmentosum</i> via Estrogen Receptor α-Dependent Signaling Pathways.<i>Acer tegmentosum</i>, a deciduous tree belonging to Aceraceae, has been used in traditional oriental medicine for treating hepatic disorders, such as hepatitis, cirrhosis, and liver cancer. We evaluated the estrogen-like effects of <i>A. tegmentosum</i> using an estrogen receptor (ER)-positive breast cancer cell line, namely MCF-7, to identify potential phytoestrogens and found that an aqueous extract of <i>A. tegmentosum</i> promoted cell proliferation in MCF-7 cells. Five phenolic compounds (<b>1</b>-<b>5</b>) were separated and identified from the active fraction using bioassay-guided fractionation of crude <i>A. tegmentosum</i> extract and phytochemical analysis. The chemical structures of the compounds were characterized as vanillic acid (<b>1</b>), 4-hydroxy-benzoic acid (<b>2</b>), syringic acid (<b>3</b>), isoscopoletin (<b>4</b>), and (<i>E</i>)-ferulic acid (<b>5</b>) based on the analysis of their nuclear magnetic resonance spectra and liquid chromatography-mass spectrometry data. All five compounds were evaluated using an E-screen assay for their estrogen-like effects on MCF-7 cells. Among the tested compounds, only 4-hydroxy-benzoic acid (<b>2</b>) promoted the proliferation of MCF-7 cells, which was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of 4-hydroxy-benzoic acid (<b>2</b>) was evaluated via western blotting analysis to determine the expression levels of extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), serine/threonine kinase (AKT), and ERα. Our results demonstrated that 4-hydroxy-benzoic acid (<b>2</b>) induced the increase in the protein expression levels of p-ERK, p-AKT, p-PI3K, and p-Erα, concentration dependently. Collectively, these experimental results suggest that 4-hydroxy-benzoic acid (<b>2</b>) is responsible for the estrogen-like effects of <i>A. tegmentosum</i> and may potentially aid in the control of estrogenic effects during menopause.2022-01-01T00:00:00Z2022 Dec2025-04-19T06:37:15.207Z2025-04-19T06:37:15.207ZS-EPMC97402173650142610.3390/plants11233387