{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:17Z","timestamp":1785422717989,"version":"3.56.0"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Centre for Complementary and Integrative Health","award":["R01 AT008824"],"award-info":[{"award-number":["R01 AT008824"]}]},{"award":["R01 AT008824"],"award-info":[{"award-number":["R01 AT008824"]}],"id":[{"id":"https:\/\/ror.org\/00190t495","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Botanical supplements are increasingly investigated for their potential to address women\u2019s health concerns. Compounds that modulate progesterone receptor (PR) signaling may help manage gynecologic disorders such as endometriosis, uterine hyperplasia, and preterm birth. Because PR ligands often cross-react with the glucocorticoid receptor (GR), this study examined two botanical compounds, paeoniflorin from Paeonia lactiflora (white peony root) and isoorientin from Vitex agnus-castus (chasteberry), that were identified as modulators of GR or PR signaling. Methods: Luciferase reporter assays were performed in OVCAR5, Ishikawa PR-B, and T47D A1-2 cells to evaluate GR and PR signaling. GR target gene expression was measured by qPCR. A receptor binding assay and computational docking were used to assess interaction with GR. Adipogenesis was evaluated in 3T3-L1 cells using Oil Red O staining and FABP4 protein expression by Western blot. Results: Paeoniflorin and isoorientin inhibited dexamethasone-induced GR signaling in OVCAR5 and Ishikawa PR-B cells. In T47D A1-2 cells, a variant of T47D engineered to express GR, both compounds blocked luciferase induction stimulated by progesterone; this effect was not observed in the parental line that expresses PR but lacks GR. In OVCAR5 cells, paeoniflorin or isoorientin combined with dexamethasone downregulated GILZ and DUSP1\/MKP1 mRNA. Isoorientin directly bound GR, and computational analysis supported potential binding poses. Both compounds also reduced lipid accumulation during 3T3-L1 adipocyte differentiation and decreased FABP4 expression, consistent with GR antagonist activity and reduced adipogenesis. Conclusions: These findings identify paeoniflorin and isoorientin as botanical modulators that suppress GR signaling and limit GR-dependent adipogenic responses across multiple cell-based models under controlled in vitro conditions.<\/jats:p>","DOI":"10.3390\/nu18101491","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T20:14:16Z","timestamp":1778530456000},"page":"1491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Isoorientin and Paeoniflorin as Botanical Glucocorticoid Receptor Modulators from White Peony and Chasteberry"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2396-9132","authenticated-orcid":false,"given":"Rasha M.","family":"Bashatwah","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA"},{"name":"Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8020-7006","authenticated-orcid":false,"given":"Luke T.","family":"Jesikiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1998-403X","authenticated-orcid":false,"given":"Alyssa L.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-347X","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Villegas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1372-3887","authenticated-orcid":false,"given":"Brian T.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-6847","authenticated-orcid":false,"given":"Joanna E.","family":"Burdette","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13643-021-01882-4","article-title":"Acceptance and use of complementary and alternative medicine among medical specialists: A 15-year systematic review and data synthesis","volume":"11","author":"Phutrakool","year":"2022","journal-title":"Syst. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1021\/acs.jnatprod.1c00835","article-title":"Irilone, a Red Clover Isoflavone, Combined with Progesterone Enhances PR Signaling through the Estrogen and Glucocorticoid Receptors","volume":"84","author":"Austin","year":"2021","journal-title":"J. Nat. Prod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1093\/emboj\/17.7.2008","article-title":"Activation of the Src\/p21ras\/Erk pathway by progesterone receptor via cross-talk with estrogen receptor","volume":"17","author":"Migliaccio","year":"1998","journal-title":"EMBO J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"589","DOI":"10.2147\/IJWH.S224159","article-title":"The Role Of Progestogens In Threatened And Idiopathic Recurrent Miscarriage","volume":"11","author":"Arab","year":"2019","journal-title":"Int. J. Women\u2019s Health"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-S\u00e1enz, M., Ibarra-Salce, R., Pozos-Varela, F.J., Mena-Ureta, T.S., Flores-Villag\u00f3mez, S., Santana-Mata, M., De Los Santos-Aguilar, R.G., Uribe-Cort\u00e9s, D., and Ferreira-Hermosillo, A. (2023). Understanding progestins: From basics to clinical applicability. J. Clin. Med., 12.","DOI":"10.3390\/jcm12103388"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00404-021-06380-5","article-title":"Endometrial hyperplasia as a risk factor of endometrial cancer","volume":"306","author":"Nees","year":"2022","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/s41419-021-03893-4","article-title":"Noncanonical functions of glucocorticoids: A novel role for glucocorticoids in performing multiple beneficial functions in endometrial stem cells","volume":"12","author":"Park","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"900","DOI":"10.2337\/db13-0436","article-title":"FABP4 attenuates PPAR\u03b3 and adipogenesis and is inversely correlated with PPAR\u03b3 in adipose tissues","volume":"63","author":"Rudich","year":"2014","journal-title":"Diabetes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1093\/emboj\/cdg218","article-title":"Stimulation of preadipocyte differentiation by steroid through targeting of an HDAC1 complex","volume":"22","author":"Wu","year":"2003","journal-title":"EMBO J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Panayiotopoulos, A., Bhangoo, A., Khurana, D., Ten, S., Michl, J., and Ghanny, S. (2020). Glucocorticoid Resistance in Premature Adrenarche and PCOS: From Childhood to Adulthood. J. Endocr. Soc., 4.","DOI":"10.1210\/jendso\/bvaa111"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101373","DOI":"10.32527\/2018\/101373","article-title":"Glucocorticoid Receptor and Adipocyte Biology","volume":"5","author":"Lee","year":"2018","journal-title":"Nucl. Recept. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pecci, A., Ogara, M.F., Sanz, R.T., and Vicent, G.P. (2022). Choosing the right partner in hormone-dependent gene regulation: Glucocorticoid and progesterone receptors crosstalk in breast cancer cells. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1037177"},{"key":"ref_13","unstructured":"Laudet, V., and Gronemeyer, H. (2002). The Nuclear Receptor Factsbook, Gulf Professional Publishing."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/s41467-018-02856-2","article-title":"Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer","volume":"9","author":"Severson","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12672-020-00382-6","article-title":"Baicalein Is a Phytohormone that Signals Through the Progesterone and Glucocorticoid Receptors","volume":"11","author":"Austin","year":"2020","journal-title":"Horm. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/ptr.1905","article-title":"Common traditional Chinese medicinal herbs for dysmenorrhea","volume":"20","author":"Jia","year":"2006","journal-title":"Phytother. Res. PTR"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"348","DOI":"10.5653\/cerm.2024.07374","article-title":"Formulation of Paeonia lactiflora root extract can induce atrophy of endometriotic lesions and accelerate embryo implantation following in vitro fertilization in endometriosis: An experimental study","volume":"52","author":"Abdolmaleki","year":"2025","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1007\/s43032-024-01472-4","article-title":"Correction: Network Pharmacology Was Used to Predict the Active Components and Prospective Targets of Paeoniae Radix Alba for Treatment in Endometriosis","volume":"31","author":"Sun","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7084","DOI":"10.18632\/aging.202564","article-title":"Paeoniflorin attenuates DHEA-induced polycystic ovary syndrome via inactivation of TGF-\u03b21\/Smads signaling pathway in vivo","volume":"13","author":"Zhou","year":"2021","journal-title":"Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jep.2018.09.006","article-title":"Paeoniflorin extract reverses dexamethasone-induced testosterone over-secretion through downregulation of cytochrome P450 17A1 expression in primary murine theca cells","volume":"229","author":"Ong","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","first-page":"439","article-title":"Paeoniflorin regulates the hypothalamic-pituitary-adrenal axis negative feedback in a rat model of post-traumatic stress disorder","volume":"23","author":"Chen","year":"2020","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shaw, S., Wyatt, K., Campbell, J., Ernst, E., and Thompson-Coon, J. (2018). Vitex agnus castus for premenstrual syndrome. Cochrane Database Syst. Rev., 2018.","DOI":"10.1002\/14651858.CD004632.pub2"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1136\/bmj.322.7279.134","article-title":"Treatment for the premenstrual syndrome with agnus castus fruit extract: Prospective, randomised, placebo controlled study","volume":"322","author":"Schellenberg","year":"2001","journal-title":"BMJ"},{"key":"ref_24","first-page":"348","article-title":"Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications","volume":"10","author":"Wuttke","year":"2003","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_25","first-page":"562","article-title":"Vitex agnus-castus extracts for female reproductive disorders: A systematic review of clinical trials","volume":"79","author":"Burger","year":"2013","journal-title":"Planta Med."},{"key":"ref_26","first-page":"18","article-title":"Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry)","volume":"11","author":"Liu","year":"2004","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1021\/jf0014157","article-title":"Evaluation of Estrogenic Activity of Plant Extracts for the Potential Treatment of Menopausal Symptoms","volume":"49","author":"Liu","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1248\/cpb.c13-00588","article-title":"Quality evaluation of medicinal products and health foods containing chaste berry (Vitex agnus-castus) in Japanese, European and American markets","volume":"62","author":"Fukahori","year":"2014","journal-title":"Chem. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s12672-013-0150-1","article-title":"Endocrine disrupting activities of the flavonoid nutraceuticals luteolin and quercetin","volume":"4","author":"Nordeen","year":"2013","journal-title":"Horm. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/107155760301000110","article-title":"Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines","volume":"10","author":"Blok","year":"2003","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100037","DOI":"10.1016\/j.metop.2020.100037","article-title":"Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes","volume":"6","author":"Ziqubu","year":"2020","journal-title":"Metab. Open"},{"key":"ref_32","first-page":"805","article-title":"Inhibition of dexamethasone-induced cytoskeletal changes in cultured human trabecular meshwork cells by tetrahydrocortisol","volume":"37","author":"Clark","year":"1996","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_33","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian 09, Gaussian, Inc.. Available online: https:\/\/gaussian.com\/g09citation\/."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jmb.2009.11.011","article-title":"Molecular Switch in the Glucocorticoid Receptor: Active and Passive Antagonist Conformations","volume":"395","author":"Schoch","year":"2010","journal-title":"J. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1093\/bioinformatics\/btg362","article-title":"ModLoop: Automated modeling of loops in protein structures","volume":"19","author":"Fiser","year":"2003","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"W368","DOI":"10.1093\/nar\/gki464","article-title":"H++: A server for estimating p K as and adding missing hydrogens to macromolecules","volume":"33","author":"Gordon","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_38","unstructured":"Case, D.A., Aktulga, H.M., Belfon, K., Ben-Shalom, I.Y., Berryman, J.T., Brozell, S.R., Cerutti, D.S., Cheatham, T.E., Cisneros, G.A., and Cruzeiro, V.W.D. (2022). Amber 2022, University of California."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general amber force field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N log (N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_43","unstructured":"(The PyMOL Molecular Graphics System, 2024). The PyMOL Molecular Graphics System, Version 3.0.0."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA. py: An efficient program for end-state free energy calculations","volume":"8","author":"Miller","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ronchetti, S., Migliorati, G., and Riccardi, C. (2015). GILZ as a Mediator of the Anti-Inflammatory Effects of Glucocorticoids. Front. Endocrinol., 6.","DOI":"10.3389\/fendo.2015.00170"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/j.bbadis.2013.05.022","article-title":"Protein tyrosine phosphatase variants in human hereditary disorders and disease susceptibilities","volume":"1832","author":"Hendriks","year":"2013","journal-title":"Biochim. Et. Biophys. Acta Mol. Basis Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ziqubu, K., Muller, C.J.F., Dludla, P.V., Mthembu, S.X.H., Obonye, N., Louw, J., Kappo, A.P., Silvestri, S., Orlando, P., and Tiano, L. (2020). Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes. Molecules, 25.","DOI":"10.3390\/molecules25081773"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.fitote.2013.08.010","article-title":"Effects of paeoniflorin on tumor necrosis factor-\u03b1-induced insulin resistance and changes of adipokines in 3T3-L1 adipocytes","volume":"91","author":"Kong","year":"2013","journal-title":"Fitoterapia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.mce.2011.04.021","article-title":"Steroid receptor coactivators 1, 2, and 3: Critical regulators of nuclear receptor activity and steroid receptor modulator (SRM)-based cancer therapy","volume":"348","author":"Johnson","year":"2012","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1021\/acs.jcim.9b00776","article-title":"Structural Insights into the Ligand Binding Domain of the Glucocorticoid Receptor: A Molecular Dynamics Study","volume":"60","author":"Alves","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.1128\/MCB.23.11.3763-3773.2003","article-title":"Progesterone and glucocorticoid receptors recruit distinct coactivator complexes and promote distinct patterns of local chromatin modification","volume":"23","author":"Li","year":"2003","journal-title":"Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1002\/cncr.11760","article-title":"Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression","volume":"98","author":"Uchikawa","year":"2003","journal-title":"Cancer"},{"key":"ref_53","first-page":"4","article-title":"Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling","volume":"9","author":"Singhal","year":"2017","journal-title":"Oncotarget"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1073\/pnas.0300372101","article-title":"Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects","volume":"101","author":"Schottelius","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Scheschowitsch, K., Leite, J.A., and Assreuy, J. (2017). New Insights in Glucocorticoid Receptor Signaling-More Than Just a Ligand-Binding Receptor. Front. Endocrinol., 8.","DOI":"10.3389\/fendo.2017.00016"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1158\/1535-7163.MCT-16-0923","article-title":"Selective Glucocorticoid Receptor Modulators (SGRMs) Delay Castrate-Resistant Prostate Cancer Growth","volume":"16","author":"Kach","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Pivonello, R., Munster, P.N., Terzolo, M., Ferrigno, R., Simeoli, C., Puglisi, S., Bali, U., and Moraitis, A.G. (2021). Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.793262"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"100741","DOI":"10.1016\/j.mcpro.2024.100741","article-title":"Selective Modulation of the Human Glucocorticoid Receptor Compromises GR Chromatin Occupancy and Recruitment of p300\/CBP and the Mediator Complex","volume":"23","author":"Verhee","year":"2024","journal-title":"Mol. Cell Proteom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"22748","DOI":"10.1074\/jbc.M212711200","article-title":"The three-dimensional structures of antagonistic and agonistic forms of the glucocorticoid receptor ligand-binding domain: RU-486 induces a transconformation that leads to active antagonism","volume":"278","author":"Kauppi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.bpc.2007.03.013","article-title":"Agonist versus antagonist induce distinct thermodynamic modes of co-factor binding to the glucocorticoid receptor","volume":"128","author":"Kroe","year":"2007","journal-title":"Biophys. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/0002-9378(86)90365-0","article-title":"Possible mechanism of steroid action of the plant herb extracts glycyrrhizin, glycyrrhetinic acid, and paeoniflorin: Inhibition by plant herb extracts of steroid protein binding in the rabbit","volume":"155","author":"Tamaya","year":"1986","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_62","first-page":"907","article-title":"Effect of paeoniflorin on level of glucocorticoid receptor of peripheral blood monocytes in rats of collagen-induced arthritis","volume":"39","author":"Yi","year":"2014","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1210\/jc.2004-0395","article-title":"Adipose tissue as an endocrine organ","volume":"89","author":"Kershaw","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1073\/pnas.0812308106","article-title":"Discovery of selective glucocorticoid receptor modulators by multiplexed reporter screening","volume":"106","author":"Gerber","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/10\/1491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T20:19:41Z","timestamp":1778530781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/10\/1491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":64,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["nu18101491"],"URL":"https:\/\/doi.org\/10.3390\/nu18101491","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]}}}