Estrogenic Activity of 4-Hydroxy-Benzoic Acid from Acer tegmentosum via Estrogen Receptor alpha-Dependent Signaling Pathwaysopen access
- Authors
- Nguyen, Quynh Nhu; Lee, Seoung Rak; Kim, Baolo; Hong, Joo-Hyun; Jang, Yoon Seo; Lee, Da Eun; Pang, Changhyun; Kang, Ki Sung; Kim, Ki Hyun
- Issue Date
- Dec-2022
- Publisher
- MDPI
- Keywords
- Acer tegmentosum; 4-hydroxy-benzoic acid; phytoestrogens; estrogen receptor
- Citation
- PLANTS-BASEL, v.11, no.23
- Journal Title
- PLANTS-BASEL
- Volume
- 11
- Number
- 23
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/86684
- DOI
- 10.3390/plants11233387
- ISSN
- 2223-7747
- Abstract
- Acer tegmentosum, 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 A. tegmentosum using an estrogen receptor (ER)-positive breast cancer cell line, namely MCF-7, to identify potential phytoestrogens and found that an aqueous extract of A. tegmentosum promoted cell proliferation in MCF-7 cells. Five phenolic compounds (1-5) were separated and identified from the active fraction using bioassay-guided fractionation of crude A. tegmentosum extract and phytochemical analysis. The chemical structures of the compounds were characterized as vanillic acid (1), 4-hydroxy-benzoic acid (2), syringic acid (3), isoscopoletin (4), and (E)-ferulic acid (5) 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 (2) 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 (2) 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 ER alpha. Our results demonstrated that 4-hydroxy-benzoic acid (2) induced the increase in the protein expression levels of p-ERK, p-AKT, p-PI3K, and p-Er alpha, concentration dependently. Collectively, these experimental results suggest that 4-hydroxy-benzoic acid (2) is responsible for the estrogen-like effects of A. tegmentosum and may potentially aid in the control of estrogenic effects during menopause.
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