{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:33:20Z","timestamp":1787765600597,"version":"build-2784847793"},"reference-count":67,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2023R141"],"award-info":[{"award-number":["PNURSP2023R141"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, we examined the sub-acute toxicity of quercetin and ferulic acid and evaluated their effects on protein, cholesterol, and estrogen levels in vivo. Six groups of female Wistar rats were fed by gavage. The first and second groups represent the positive (Clomiphene citrate 10 mg\/kg) and negative (NaCl 0.9%) control groups, while the other groups received quercetin and ferulic acid at doses of 5 and 10 mg\/kg\/day for 28 days. The sub-acute toxicity was monitored by examining the weights, biochemical parameters (AST, ALT, ALP, urea, and CREA), and histological changes in the kidneys and liver of the treated animals. Furthermore, the in vivo estrogenic effects were studied in terms of the serum and ovarian cholesterol levels, serum estradiol, and uterine proteins. Finally, Docking studies were conducted to evaluate the binding affinity of quercetin and ferulic acid for alpha and beta estrogen receptors. Results showed that both compounds were devoid of any signs of nephrotoxicity or hepatotoxicity. Additionally, quercetin and ferulic acid caused significant estrogenic effects evidenced by an increase of 8.7 to 22.48% in serum estradiol, though to a lesser amount than in the reference drug-treated group (64.21%). Moreover, the two compounds decreased the serum cholesterol levels (12.26\u201332.75%) as well as the ovarian cholesterol level (11.9% to 41.50%) compared to the negative control. The molecular docking in estrogen alpha and estrogen beta active sites showed high affinity of quercetin (\u221210.444 kcal\/mol for estrogen alpha and \u221210.662 kcal\/mol for estrogen beta) and ferulic acid (\u22126.377 kcal\/mol for estrogen alpha and \u22126.3 kcal\/mol for estrogen beta) to these receptors. This study provides promising insights into the potential use of quercetin as a therapeutic agent for the management of female fertility issues.<\/jats:p>","DOI":"10.3390\/molecules28135112","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T01:14:12Z","timestamp":1688087652000},"page":"5112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Quercetin and Ferulic Acid Elicit Estrogenic Activities In Vivo and In Silico"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8068-3627","authenticated-orcid":false,"given":"Meryem","family":"Slighoua","sequence":"first","affiliation":[{"name":"Laboratory of Biotechnology, Environment, Agro-Food, and Health (LBEAS), Faculty of Sciences, University 7 Sidi-Mohamed-Ben-Abdellah (USMBA), Fez 30050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Ez-Zahra","family":"Amrati","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology, Environment, Agro-Food, and Health (LBEAS), Faculty of Sciences, University 7 Sidi-Mohamed-Ben-Abdellah (USMBA), Fez 30050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6614-9594","authenticated-orcid":false,"given":"Mohamed","family":"Chebaibi","sequence":"additional","affiliation":[{"name":"Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy of Fez, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-941X","authenticated-orcid":false,"given":"Ismail","family":"Mahdi","sequence":"additional","affiliation":[{"name":"AgroBioSciences Research Division, College for Sustainable Agriculture and Environmental Science, Mohammed VI Polytechnic University, Lot 660-Hay Moulay Rachid, Ben Guerir 43150, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4706-4311","authenticated-orcid":false,"given":"Omkulthom","family":"Al Kamaly","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-7298","authenticated-orcid":false,"given":"Khadija","family":"El Ouahdani","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology, Environment, Agro-Food, and Health (LBEAS), Faculty of Sciences, University 7 Sidi-Mohamed-Ben-Abdellah (USMBA), Fez 30050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-5289","authenticated-orcid":false,"given":"Aziz","family":"Drioiche","sequence":"additional","affiliation":[{"name":"Laboratory of Innovative Materials and Biotechnology of Natural Resources, Faculty of Sciences, Moulay 19 Ismail University, Meknes 50070, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Bousta","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology, Environment, Agro-Food, and Health (LBEAS), Faculty of Sciences, University 7 Sidi-Mohamed-Ben-Abdellah (USMBA), Fez 30050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.jep.2009.10.021","article-title":"Fertility Inducing Effect of Aerial Parts of Coccinia cordifolia L. in Female Rats","volume":"127","author":"Jha","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_2","first-page":"379","article-title":"A Review of Female Infertility; Important Etiological Factors and Management","volume":"2","author":"Olooto","year":"2012","journal-title":"J. Microbiol. Biotechnol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","article-title":"Fertility and Infertility: Definition and Epidemiology","volume":"62","author":"Wyns","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1442-2042.2009.02280.x","article-title":"Role of Antioxidants in the Treatment of Male Infertility","volume":"16","author":"Kefer","year":"2009","journal-title":"Int. J. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.58397\/ashkmdc.v25i01.224","article-title":"The Role Of IGF-I in Females Selected for Assisted Reproductive Technique (Art)","volume":"25","author":"Salahuddin","year":"2020","journal-title":"Ann. Abbasi Shaheed Hosp. Karachi Med. Dent. Coll."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s43032-020-00312-5","article-title":"Ameliorating Effects of Natural Antioxidant Compounds on Female Infertility: A Review","volume":"28","author":"Bhardwaj","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_7","unstructured":"De La Rochebrochard, E. (2004). M\u00e9dicalisation de l\u2019Infertilit\u00e9: Quelle Est la Situation Mondiale du Nord au Sud?, Universitaires de Louvain City."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fakeye, T.O., Adisa, R., and Musa, I.E. (2009). Attitude and Use of Herbal Medicines among Pregnant Women in Nigeria. BMC Complement. Altern. Med., 9.","DOI":"10.1186\/1472-6882-9-53"},{"key":"ref_9","first-page":"2041","article-title":"Ethnopharmacological Survey of Medicinal Plants Used in the Traditional Treatment of Female Infertility in Fez Region, Morocco","volume":"6","author":"Slighoua","year":"2019","journal-title":"Phytoth\u00e9rapie"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jep.2014.12.014","article-title":"Effect of the Aqueous Extract of Senecio Biafrae (Oliv. & Hiern) J. Moore on Some Fertility Parameters in Immature Female Rat","volume":"161","author":"Lienou","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.sajb.2021.11.014","article-title":"Pharmacological Effects of Lavandula officinalis Chaix and Its Polyphenols: Focus on Their in Vivo Estrogenic and Anti-Inflammatory Properties","volume":"146","author":"Slighoua","year":"2022","journal-title":"S. Afr. J. Bot."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113290","DOI":"10.1016\/j.jep.2020.113290","article-title":"Assessment of in Vivo Estrogenic and Anti-Inflammatory Activities of the Hydro-Ethanolic Extract and Polyphenolic Fraction of Parsley (Petroselinum sativum Hoffm.)","volume":"265","author":"Slighoua","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1210\/endo.139.10.6216","article-title":"Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor \u03b2","volume":"139","author":"Kuiper","year":"1998","journal-title":"Endocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0891-5849(98)00190-7","article-title":"Quantitative Structure-Activity Relationship Analysis of Phenolic Antioxidants","volume":"26","author":"Lien","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0006-8993(94)91431-1","article-title":"Myricetin and Quercetin, the Flavonoid Constituents of Ginkgo biloba Extract, Greatly Reduce Oxidative Metabolism in Both Resting and Ca2+-Loaded Brain Neurons","volume":"635","author":"Oyama","year":"1994","journal-title":"Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.yfrne.2010.03.003","article-title":"The Pros and Cons of Phytoestrogens","volume":"31","author":"Patisaul","year":"2010","journal-title":"Front. Neuroendocrinol."},{"key":"ref_17","first-page":"185","article-title":"Phytoestrogens in Health and Disease","volume":"54","author":"Davis","year":"1999","journal-title":"Recent Prog. Horm. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.phymed.2009.01.005","article-title":"Antiosteoporotic Activity of Phenolic Compounds from Curculigo Orchioides","volume":"16","author":"Jiao","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.5152\/etd.2016.0005","article-title":"Estrogen-like Activity of Quercetin in Female Rats","volume":"38","author":"Erol","year":"2016","journal-title":"Erciyes Med. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"153736","DOI":"10.1016\/j.phymed.2021.153736","article-title":"A Review on Pharmacological Activities and Synergistic Effect of Quercetin with Small Molecule Agents","volume":"92","author":"Zou","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_21","first-page":"700","article-title":"Ferulic Acid-A Comprehensive Pharmacology of an Important Bioflavonoid","volume":"3","author":"Gohil","year":"2012","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.fct.2013.12.024","article-title":"Ferulic Acid: Pharmacological and Toxicological Aspects","volume":"65","author":"Mancuso","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1208\/ps060214","article-title":"Acute and Subchronic (28-Day) Oral Toxicity Study in Rats Fed with Novel Surfactants","volume":"6","author":"Bidhe","year":"2004","journal-title":"AAPS PharmSci"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1006\/abbi.1999.1516","article-title":"Inhibitory Effect of Quercetin Metabolites and Their Related Derivatives on Copper Ion-Induced Lipid Peroxidation in Human Low-Density Lipoprotein","volume":"372","author":"Yamamoto","year":"1999","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1182\/blood.V83.9.2654.2654","article-title":"Changes in the Localization of Catalase during Differentiation of Neutrophilic Granulocytes","volume":"83","author":"Ballinger","year":"1994","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0014-5793(98)00709-1","article-title":"Quercetin Metabolites Inhibit Copper Ion-Induced Lipid Peroxidation in Rat Plasma","volume":"430","author":"Piskula","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1006\/taap.1994.1059","article-title":"Quercetin Increases the Severity of Estradiol-Induced Tumorigenesis in Hamster Kidney","volume":"125","author":"Zhu","year":"1994","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/j.1365-2362.2006.01676.x","article-title":"Modulation of HER2 Expression by Ferulic Acid on Human Breast Cancer MCF7 Cells","volume":"36","author":"Chang","year":"2006","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1172\/JCI116985","article-title":"Raloxifene (LY139481 HCI) Prevents Bone Loss and Reduces Serum Cholesterol without Causing Uterine Hypertrophy in Ovariectomized Rats","volume":"93","author":"Black","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1532-0456(03)00140-6","article-title":"Antidiabetic Effects of Quercetin in Streptozocin-Induced Diabetic Rats","volume":"135","author":"Vessal","year":"2003","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bandera, E.V., King, M., Chandran, U., Paddock, L.E., Rodriguez-Rodriguez, L., and Olson, S.H. (2011). Phytoestrogen Consumption from Foods and Supplements and Epithelial Ovarian Cancer Risk: A Population-Based Case Control Study. BMC Womens Health, 11.","DOI":"10.1186\/1472-6874-11-40"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"705","DOI":"10.5306\/wjco.v5.i4.705","article-title":"Phytoestrogens and Prevention of Breast Cancer: The Contentious Debate","volume":"5","author":"Bilal","year":"2014","journal-title":"World J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0960-0760(97)00092-7","article-title":"Effects of Genistein and Lavendustin on Reproductive Processes in Domestic Animals in Vitro","volume":"63","author":"Makarevich","year":"1997","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0960-0760(95)00261-8","article-title":"Effects of Flavonoids on Aromatase Activity, an in Vitro Study","volume":"57","author":"Pelissero","year":"1996","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1289\/ehp.00108701","article-title":"Genistein: Does It Prevent or Promote Breast Cancer?","volume":"108","author":"Bouker","year":"2000","journal-title":"Environ. Health Perspect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1600-0749.2004.00167.x","article-title":"Novel Approach for Evaluation of Estrogenic and Anti-Estrogenic Activities of Genistein and Daidzein Using B16 Melanoma Cells and Dendricity Assay","volume":"17","author":"Miyazaki","year":"2004","journal-title":"Pigment Cell Res."},{"key":"ref_37","first-page":"297","article-title":"Phytoestrogens","volume":"83","author":"Murkies","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1289\/ehp.10538","article-title":"Phytoestrogens and Breast Cancer Prevention: Possible Mechanisms of Action","volume":"116","author":"Mense","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2174\/1389203718666170111121255","article-title":"Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer","volume":"19","author":"Hsieh","year":"2018","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jsbmb.2004.12.041","article-title":"Comparative Study of Oestrogenic Properties of Eight Phytoestrogens in MCF7 Human Breast Cancer Cells","volume":"94","author":"Matsumura","year":"2005","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1055\/s-0028-1088304","article-title":"Selective Estrogen Receptor Modulators and Phytoestrogens","volume":"74","author":"Oseni","year":"2008","journal-title":"Planta Med."},{"key":"ref_42","first-page":"ra47","article-title":"Perinuclear Mitochondrial Clustering Creates an Oxidant-Rich Nuclear Domain Required for Hypoxia-Induced Transcription","volume":"5","author":"Pastukh","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1152\/physrev.00041.2010","article-title":"Hypoxic Pulmonary Vasoconstriction","volume":"92","author":"Sylvester","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1152\/japplphysiol.01095.2005","article-title":"Influence of Sex Steroid Hormones on Cerebrovascular Function","volume":"101","author":"Krause","year":"2006","journal-title":"J. Appl. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ejphar.2014.07.057","article-title":"Phytoestrogens and Their Effects","volume":"741","author":"Sirotkin","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"521313","DOI":"10.1155\/2014\/521313","article-title":"Receptors of Hypothalamic-Pituitary-Ovarian-Axis Hormone in Uterine Myomas","volume":"2014","author":"Plewka","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.canlet.2005.01.021","article-title":"Estrogen Receptor Beta, a Possible Tumor Suppressor Involved in Ovarian Carcinogenesis","volume":"231","author":"Lazennec","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5936","DOI":"10.1073\/pnas.97.11.5936","article-title":"Estrogen Receptor (ER) \u03b2, a Modulator of ER\u03b1 in the Uterus","volume":"97","author":"Weihua","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2014.00001","article-title":"Role of Estrogen Receptors and G Protein-Coupled Estrogen Receptor in Regulation of Hypothalamus\u2013Pituitary\u2013Testis Axis and Spermatogenesis","volume":"5","author":"Chimento","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1002\/fsn3.2523","article-title":"Female Infertility and Herbal Medicine: An Overview of the New Findings","volume":"9","author":"Akbaribazm","year":"2021","journal-title":"Food Sci. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s11655-016-2510-5","article-title":"Chinese Medicine as Complementary Therapy for Female Infertility","volume":"23","author":"Xia","year":"2017","journal-title":"Chin. J. Integr. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8643","DOI":"10.1021\/jf101510z","article-title":"Apoptotic Effect of Quercetin on HT-29 Colon Cancer Cells via the AMPK Signaling Pathway","volume":"58","author":"Kim","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1002\/jcp.22917","article-title":"The Pro-apoptotic Effect of Quercetin in Cancer Cell Lines Requires ER\u03b2-dependent Signals","volume":"227","author":"Bulzomi","year":"2012","journal-title":"J. Cell Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9437","DOI":"10.1007\/s13277-015-3689-3","article-title":"Assessment of the Anticancer Mechanism of Ferulic Acid via Cell Cycle and Apoptotic Pathways in Human Prostate Cancer Cell Lines","volume":"36","author":"Dodurga","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1093\/jn\/136.11.2715","article-title":"Quercetin Induces Apoptosis via Caspase Activation, Regulation of Bcl-2, and Inhibition of PI-3-Kinase\/Akt and ERK Pathways in a Human Hepatoma Cell Line (HepG2)","volume":"136","author":"Bravo","year":"2006","journal-title":"J. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11010-014-2169-1","article-title":"ELF-MF Attenuates Quercetin-Induced Apoptosis in K562 Cells through Modulating the Expression of Bcl-2 Family Proteins","volume":"397","author":"Brisdelli","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_57","first-page":"968","article-title":"Ferulic Acid Inhibits Proliferation and Promotes Apoptosis via Blockage of PI3K\/Akt Pathway in Osteosarcoma Cell","volume":"8","author":"Wang","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_58","unstructured":"(2019, December 21). Union, P.O. of the E. Council Directive 86\/609\/EEC of 24 November 1986 on the Approximation of Laws, Regulations and Administrative Provisions of the Member States Regarding the Protection of Animals Used for Experimental and Other Scientific Purposes, CELEX1. Available online: https:\/\/op.europa.eu:443\/en\/publication-detail\/-\/publication\/cc3a8ccb-5a30-4b6e-8da8-b13348caeb0c\/language-en."},{"key":"ref_59","first-page":"546","article-title":"Effects of Daily Oral Administration of Quercetin Chalcone and Modified Citrus Pectin on Implanted Colon-25 Tumor Growth in Balb-c Mice","volume":"5","author":"Hayashi","year":"2000","journal-title":"Altern. Med. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1248\/jhs.53.351","article-title":"Oral Acute and Subacute Toxicity Studies with Kalpaamruthaa, a Modified Indigenous Preparation, on Rats","volume":"53","author":"Mythilypriya","year":"2007","journal-title":"J. Health Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s002040100214","article-title":"Feasibility and Potential Gains of Enhancing the Subacute Rat Study Protocol (OECD Test Guideline No. 407) by Additional Parameters Selected to Determine Endocrine Modulation. A Pre-Validation Study to Determine Endocrine-Mediated Effects of the Antiandrogenic Drug Flutamide","volume":"75","author":"Andrews","year":"2001","journal-title":"Arch. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S1567-1739(02)00178-5","article-title":"Co-Immobilization of Cholesterol Esterase, Cholesterol Oxidase and Peroxidase onto Alkylamine Glass Beads for Measurement of Total Cholesterol in Serum","volume":"3","author":"Suman","year":"2003","journal-title":"Curr. Appl. Phys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1128\/jcm.10.3.317-321.1979","article-title":"Enzyme-Linked Fluorescence Assay: Ultrasensitive Solid-Phase Assay for Detection of Human Rotavirus","volume":"10","author":"Yolken","year":"1979","journal-title":"J. Clin. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1016\/S0024-3205(01)01031-1","article-title":"Cryopreservation of Rat Precision-Cut Liver Slices by Ultrarapid Freezing: Influence on Phase I and II Metabolism and on Cell Viability upon Incubation for 24 Hours","volume":"68","author":"Vanhulle","year":"2001","journal-title":"Life Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1210\/en.2016-1916","article-title":"Defining the Role of Estrogen Receptor \u03b2 in the Regulation of Female Fertility","volume":"158","author":"Rumi","year":"2017","journal-title":"Endocrinology"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Aboul-Soud, M.A., Ennaji, H., Kumar, A., Alfhili, M.A., Bari, A., Ahamed, M., Chebaibi, M., Bourhia, M., Khallouki, F., and Alghamdi, K.M. (2022). Antioxidant, Anti-Proliferative Activity and Chemical Fingerprinting of Centaurea Calcitrapa against Breast Cancer Cells and Molecular Docking of Caspase-3. Antioxidants, 11.","DOI":"10.3390\/antiox11081514"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40203-015-0008-z","article-title":"A Molecular Docking Study of Phytochemical Estrogen Mimics from Dietary Herbal Supplements","volume":"3","author":"Powers","year":"2015","journal-title":"Silico Pharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5112\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:57Z","timestamp":1760126637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,29]]},"references-count":67,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["molecules28135112"],"URL":"https:\/\/doi.org\/10.3390\/molecules28135112","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,29]]}}}