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Baicalein Is a Phytohormone that Signals Through the Progesterone and Glucocorticoid Receptors
journal contributionposted on 2022-05-06, 17:14 authored by Julia R Austin, Brenna J Kirkpatrick, Rocío Rivera Rodríguez, Michael JohnsonMichael Johnson, Daniel D Lantvit, Joanna BurdetteJoanna Burdette
While flavonoids have been studied extensively for estrogen receptor activity, they have not been well studied for their ability to modify progesterone receptor (PR) and glucocorticoid receptor (GR) signaling. Three flavonoid compounds, tangeretin, wogonin, and baicalein, were selected for testing for PR and GR activity based on their structural similarity to known phytoprogesterone-like compounds. Each compound was docked in the binding pocket of PR and GR. Of these compounds, baicalein was predicted to be most likely to bind to both receptors. A fluorescence polarization competitive binding assay for PR and GR confirmed that baicalein binds to both the PR and GR with IC50 values of 15.30 μM and 19.26 μM, respectively. In Ishikawa PR-B and T47D cells, baicalein acted as a PR antagonist in a hormone response element (HRE) luciferase (Luc) assay. In OVCAR5 cells, which only express GR, baicalein was a GR agonist via an HRE/Luc assay and induced GR target genes, FKBP5 and GILZ. RU486, a PR and GR antagonist, abrogated baicalein's activity in OVCAR5 cells, confirming baicalein's activity is mediated through the GR. In vivo, baicalein administered intraperitoneally to female mice twice a week for 4 weeks at a dose of 25 mg/kg induced the GR target gene GILZ in the reproductive tract, which was blocked by RU486. In summary, baicalein has PR antagonist and GR agonist activity in vitro and demonstrates GR agonist activity in the uterus in vivo.
Research Training in Natural Product Complementary and Alternative Medicine | Funder: National Institutes of Health (National Center for Complementary and Integrative Health) | Grant ID: T32AT007533
Botanical Derived Progestins and Their Impact on Women's Health | Funder: National Institutes of Health (National Center for Complementary and Integrative Health) | Grant ID: R01AT008824
Botanical derived progestins and their impact on women's health | Funder: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH | Grant ID: 5R01AT008824
CitationAustin, J. R., Kirkpatrick, B. J., Rodríguez, R. R., Johnson, M. E., Lantvit, D. D.Burdette, J. E. (2020). Baicalein Is a Phytohormone that Signals Through the Progesterone and Glucocorticoid Receptors. Discover Oncology, 11(2), 97-110. https://doi.org/10.1007/s12672-020-00382-6
PublisherSpringer Science and Business Media LLC
CategoriesNo categories selected
1.1 Normal biological development and functioningPhytoprogestinPhytocorticoidBotanical supplementNatural productScutellaria baicalensisAnimalsAntioxidantsFemaleFlavanonesHumansMiceMice, NudeModels, MolecularRandom AllocationReceptors, GlucocorticoidReceptors, ProgesteroneSignal TransductionTransfectionOncology and Carcinogenesis