{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:08:30Z","timestamp":1790780910701,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81473390"],"award-info":[{"award-number":["81473390"]}]},{"name":"National Natural Science Foundation of China","award":["30902014"],"award-info":[{"award-number":["30902014"]}]},{"name":"National Natural Science Foundation of China","award":["ZDXM-2022-12"],"award-info":[{"award-number":["ZDXM-2022-12"]}]},{"name":"National Natural Science Foundation of China","award":["20KJA360001"],"award-info":[{"award-number":["20KJA360001"]}]},{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization","award":["81473390"],"award-info":[{"award-number":["81473390"]}]},{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization","award":["30902014"],"award-info":[{"award-number":["30902014"]}]},{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization","award":["ZDXM-2022-12"],"award-info":[{"award-number":["ZDXM-2022-12"]}]},{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization","award":["20KJA360001"],"award-info":[{"award-number":["20KJA360001"]}]},{"name":"Natural Science Foundation of the Jiangsu Higher Education Institutions of China","award":["81473390"],"award-info":[{"award-number":["81473390"]}]},{"name":"Natural Science Foundation of the Jiangsu Higher Education Institutions of China","award":["30902014"],"award-info":[{"award-number":["30902014"]}]},{"name":"Natural Science Foundation of the Jiangsu Higher Education Institutions of China","award":["ZDXM-2022-12"],"award-info":[{"award-number":["ZDXM-2022-12"]}]},{"name":"Natural Science Foundation of the Jiangsu Higher Education Institutions of China","award":["20KJA360001"],"award-info":[{"award-number":["20KJA360001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>1,2,3,4,6-penta-O-galloyl-\u03b2-D-glucose (PGG) is the main phenolic active ingredient in Paeoniae Radix Alba, which is commonly used for the treatment of osteoporosis (OP). PGG is a potent natural antioxidant, and its effects on OP remain unknown. This study aimed to investigate the effects of PGG on promoting bone formation and explore its estrogen receptor (ER)-related mechanisms. A hydrogen peroxide-induced osteoblast apoptosis model was established in MC3T3-E1 cells. The effects of PGG were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, alkaline phosphatase (ALP) staining, RT-qPCR, and Western blot methods. Furthermore, a prednisolone-induced zebrafish OP model was employed to study the effects in vivo. ER inhibitors and molecular docking methods were used further to investigate the interactions between PGG and ERs. The results showed that PGG significantly enhanced cell viability and decreased cell apoptosis by restoring mitochondrial function, attenuating reactive oxygen species levels, decreasing the mitochondrial membrane potential, and enhancing ATP production. PGG enhanced ALP expression and activity and elevated osteogenic differentiation. PGG also promoted bone formation in the zebrafish model, and these effects were reversed by ICI182780. These results provide evidence that the effects of PGG in alleviating apoptosis and promoting bone formation may depend on ERs. As such, PGG is considered a valuable candidate for treating OP.<\/jats:p>","DOI":"10.3390\/molecules29215110","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T12:09:18Z","timestamp":1730203758000},"page":"5110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antioxidant 1,2,3,4,6-Penta-O-galloyl-\u03b2-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen Receptors"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-4439","authenticated-orcid":false,"given":"Yongqing","family":"Hua","sequence":"first","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haili","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeru","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqin","family":"Mo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8346-2246","authenticated-orcid":false,"given":"Hongyun","family":"Mao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxia","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Hong","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jff.2017.07.045","article-title":"Pentagalloylglucose (PGG): A valuable phenolic compound with functional properties","volume":"37","author":"Aguilar","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.foodchem.2008.12.020","article-title":"Antioxidant properties of 1,2,3,4,6-penta-O-galloyl-\u03b2-d-glucose from Elaeocarpus sylvestris var","volume":"115","author":"Piao","year":"2009","journal-title":"ellipticus. Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1007\/s10439-022-03093-x","article-title":"Pentagalloyl Glucose (PGG) Prevents and Restores Mechanical Changes Caused by Elastic Fiber Fragmentation in the Mouse Ascending Aorta","volume":"51","author":"Crandall","year":"2023","journal-title":"Ann. Biomed. Eng."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1039\/D3FO00997A","article-title":"Metabolic regulation and antihyperglycemic properties of diet-derived PGG through transcriptomic and metabolomic profiling","volume":"14","author":"Zhang","year":"2023","journal-title":"Food Funct."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"154192","DOI":"10.1016\/j.phymed.2022.154192","article-title":"Pentagalloylglucose suppresses the growth and migration of human nasopharyngeal cancer cells via the GSK3\u03b2\/\u03b2-catenin pathway in vitro and in vivo","volume":"102","author":"Fan","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"977","DOI":"10.32604\/biocell.2023.028402","article-title":"Network pharmacology and molecular docking identify mechanisms of medicinal plant-derived1,2,3,4,6-penta-O-galloyl-\u03b2-d-glucose treating gastric cancer","volume":"47","author":"Ren","year":"2023","journal-title":"Biocell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jpba.2016.06.044","article-title":"Influence of herbal combinations on the extraction efficiencies of chemical compounds from Cinnamomum cassia, Paeonia lactiflora, and Glycyrrhiza uralensis, the herbal components of Gyeji-tang, evaluated by HPLC method","volume":"129","author":"Kim","year":"2016","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/ptr.5653","article-title":"A Pharmacological Review of Bioactive Constituents of Paeonia lactiflora Pallas and Paeonia veitchii Lynch","volume":"30","author":"Parker","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lu, J., Hu, D., Ma, C., and Shuai, B. (2022). Advances in Our Understanding of the Mechanism of Action of Drugs (including Traditional Chinese Medicines) for the Intervention and Treatment of Osteoporosis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.938447"},{"key":"ref_10","first-page":"188","article-title":"Analysis of Common Prescriptions of Chinese Medicine Treatment of Osteoporosis","volume":"16","author":"Guo","year":"2010","journal-title":"Chin. J. Exp. Trandit. Med. Formul."},{"key":"ref_11","first-page":"254","article-title":"Comparative Analysis on Composition Principles of Traditional Chinese Medicine Prescriptions for Ankylosing Spondylitis and Osteoporosis","volume":"23","author":"Chen","year":"2017","journal-title":"J. Basic Chin. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41574-019-0282-7","article-title":"A road map for understanding molecular and genetic determinants of osteoporosis","volume":"16","author":"Yang","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1002\/jbmr.4410","article-title":"The diverse origin of bone-forming osteoblasts","volume":"36","author":"Mizoguchi","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116399","DOI":"10.1016\/j.jep.2023.116399","article-title":"Jintiange proteins promote osteogenesis and inhibit apoptosis of osteoblasts by enhancing autophagy via PI3K\/AKT and ER stress pathways","volume":"311","author":"Liu","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, C., Li, H., Li, J., Hu, J., Yang, K., and Tao, L. (2023). Oxidative stress: A common pathological state in a high-risk population for osteoporosis. Biomed. Pharmacother., 163.","DOI":"10.1016\/j.biopha.2023.114834"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.37349\/emed.2023.00124","article-title":"Oxidative stress, inflammation, dysfunctional redox homeostasis and autophagy cause age-associated diseases","volume":"4","author":"Sobhon","year":"2023","journal-title":"Explor. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/13510002.2022.2046423","article-title":"Role of mitochondrial reactive oxygen species in homeostasis regulation","volume":"27","author":"Zhang","year":"2022","journal-title":"Redox Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1016\/j.freeradbiomed.2011.02.016","article-title":"Hydrogen sulfide protects MC3T3-E1 osteoblastic cells against H2O2-induced oxidative damage\u2014Implications for the treatment of osteoporosis","volume":"50","author":"Xu","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.freeradbiomed.2022.07.013","article-title":"Nrf2 as a regulator of mitochondrial function: Energy metabolism and beyond","volume":"189","author":"Esteras","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kasai, S., Shimizu, S., Tatara, Y., Mimura, J., and Itoh, K. (2020). Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology. Biomolecules, 10.","DOI":"10.3390\/biom10020320"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Marcucci, G., Domazetovic, V., Nediani, C., Ruzzolini, J., Favre, C., and Brandi, M.L. (2023). Oxidative Stress and Natural Antioxidants in Osteoporosis: Novel Preventive and Therapeutic Approaches. Antioxidants, 12.","DOI":"10.3390\/antiox12020373"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41413-023-00308-2","article-title":"Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy","volume":"12","author":"Nie","year":"2024","journal-title":"Bone Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.omtn.2023.05.026","article-title":"Estrogen-regulated miRs in bone enhance osteoblast differentiation and matrix mineralization","volume":"33","author":"Emch","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1056\/NEJMcp1513724","article-title":"Postmenopausal Osteoporosis","volume":"374","author":"Black","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1111\/bph.15024","article-title":"Overview of treatment approaches to osteoporosis","volume":"178","author":"Langdahl","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1039\/D2TB00944G","article-title":"Antibacterial ability and osteogenic activity of polyphenol-tailored calcium silicate bone cement","volume":"10","author":"Wu","year":"2022","journal-title":"J. Mater. Chem. B"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ekiert, H., Klimek-Szczykutowicz, M., and Szopa, A. (2022). Paeonia \u00d7 suffruticosa (Moutan Peony)-A Review of the Chemical Composition, Traditional and Professional Use in Medicine, Position in Cosmetics Industries, and Biotechnological Studies. Plants, 11.","DOI":"10.3390\/plants11233379"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.freeradbiomed.2023.08.018","article-title":"5-(3\u2032,4\u2032-dihydroxyphenyl)-\u03b3-valerolactone, a microbiota metabolite of flavan-3-ols, activates SIRT1-mediated autophagy to attenuate H\u2082O\u2082-induced inhibition of osteoblast differentiation in MC3T3-E1 cells","volume":"208","author":"Chen","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/jbmr.4256","article-title":"Skeletal biology and disease modeling in zebrafish","volume":"36","author":"Dietrich","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/21691401.2019.1709851","article-title":"Protective effect of hyperoside against hydrogen peroxide-induced dysfunction and oxidative stress in osteoblastic MC3T3-E1 cells","volume":"48","author":"Qi","year":"2020","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1210\/endrev\/bnac031","article-title":"Bone Turnover Markers: Basic Biology to Clinical Applications","volume":"44","author":"Schini","year":"2023","journal-title":"Endocr. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13287-020-02085-9","article-title":"Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses","volume":"12","author":"Zhou","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Westhauser, F., Karadjian, M., Essers, C., Senger, A.S., Hagmann, S., Schmidmaier, G., and Moghaddam, A. (2019). Osteogenic differentiation of mesenchymal stem cells is enhanced in a 45S5-supplemented \u03b2-TCP composite scaffold: An in-vitro comparison of Vitoss and Vitoss BA. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212799"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1152\/physrev.00058.2021","article-title":"Mitochondria in health, disease, and aging","volume":"103","author":"Harrington","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41580-020-0210-7","article-title":"The cell biology of mitochondrial membrane dynamics","volume":"21","author":"Giacomello","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yang, F., Lin, Z.W., Huang, T.Y., Chen, T.T., Cui, J., Li, M.Y., and Hua, Y.Q. (2019). Ligustilide, a major bioactive component of Angelica sinensis, promotes bone formation via the GPR30\/EGFR pathway. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-43518-7"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"155284","DOI":"10.1016\/j.phymed.2023.155284","article-title":"Ginsenoside Rg1 modulates PI3K\/AKT pathway for enhanced osteogenesis via GPER","volume":"124","author":"Jiang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.molmed.2019.09.007","article-title":"Nrf2: Redox and Metabolic Regulator of Stem Cell State and Function","volume":"26","author":"Dai","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rosa, J.T., Laiz\u00e9, V., Gavaia, P.J., and Cancela, M.L. (2021). Fish Models of Induced Osteoporosis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.672424"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1161\/01.RES.0000050588.35034.3C","article-title":"Glucocorticoid Excess Induces Superoxide Production in Vascular Endothelial Cells and Elicits Vascular Endothelial Dysfunction","volume":"92","author":"Iuchi","year":"2003","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nature01660","article-title":"Control of osteoblast function and regulation of bone mass","volume":"423","author":"Harada","year":"2003","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s44324-024-00010-9","article-title":"Bone metabolism\u2013an underappreciated player","volume":"2","author":"Choi","year":"2024","journal-title":"NPJ Metab. Health Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41413-022-00190-4","article-title":"Mechanical regulation of bone remodeling","volume":"10","author":"Wang","year":"2022","journal-title":"Bone Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline phosphatase: Structure, expression and its function in bone mineralization","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Diao, Y., Chen, B., Wei, L., and Wang, Z. (2018). Polyphenols (S3) Isolated from Cone Scales of Pinus koraiensis Alleviate Decreased Bone Formation in Rat under Simulated Microgravity. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-30992-8"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41580-019-0173-8","article-title":"Mitochondria as multifaceted regulators of cell death","volume":"21","author":"Bock","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.cell.2019.08.004","article-title":"TNF Induces Pathogenic Programmed Macrophage Necrosis in Tuberculosis through a Mitochondrial-Lysosomal-Endoplasmic Reticulum Circuit","volume":"178","author":"Roca","year":"2019","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e107341","DOI":"10.15252\/embj.2020107341","article-title":"Too much death can kill you: Inhibiting intrinsic apoptosis to treat disease","volume":"40","author":"Li","year":"2021","journal-title":"EMBO J."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Pu, Q., Guo, X.-X., Hu, J.-J., Li, A.-L., Li, G.-G., and Li, X.-Y. (2022). Nicotinamide mononucleotide increases cell viability and restores tight junctions in high-glucose-treated human corneal epithelial cells via the SIRT1\/Nrf2\/HO-1 pathway. Biomed. Pharmacother., 147.","DOI":"10.1016\/j.biopha.2022.112659"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1210\/er.2014-1024","article-title":"Sex steroid actions in male bone","volume":"35","author":"Vanderschueren","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.cmet.2018.12.021","article-title":"Autoregulation of Osteocyte Sema3A Orchestrates Estrogen Action and Counteracts Bone Aging","volume":"29","author":"Hayashi","year":"2019","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1210\/er.2009-0024","article-title":"From estrogen-centric to aging and oxidative stress: A revised perspective of the pathogenesis of osteoporosis","volume":"31","author":"Manolagas","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1210\/endrev\/bnac017","article-title":"Estrogen receptor signaling in the immune system","volume":"44","author":"Chakraborty","year":"2023","journal-title":"Endocr. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1210\/edrv.20.3.0370","article-title":"Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us?","volume":"20","author":"Couse","year":"1999","journal-title":"Endocr. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Noirrit-Esclassan, E., Valera, M.-C., Tremollieres, F., Arnal, J.-F., Lenfant, F., Fontaine, C., and Vinel, A. (2021). Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041568"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.jnutbio.2015.07.021","article-title":"Prunetin signals via G-protein-coupled receptor, GPR30(GPER1): Stimulation of adenylyl cyclase and cAMP-mediated activation of MAPK signaling induces Runx2 expression in osteoblasts to promote bone regeneration","volume":"26","author":"Khan","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/jbmr.169","article-title":"Estrogen receptor alpha36 mediates a bone-sparing effect of 17beta-estrodiol in postmenopausal women","volume":"26","author":"Xie","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.freeradbiomed.2020.03.023","article-title":"Beyond repression of Nrf2: An update on Keap1","volume":"157","author":"Kopacz","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","article-title":"Nrf2-Keap1 signaling in oxidative and reductive stress","volume":"1865","author":"Bellezza","year":"2018","journal-title":"Biochim. Biophys. Acta-Mol. Cell Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1039\/C9FO01466G","article-title":"Effect of soybean peptides against hydrogen peroxide induced oxidative stress in HepG2 cells via Nrf2 signaling","volume":"11","author":"Yi","year":"2020","journal-title":"Food Funct."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/s12964-022-00979-0","article-title":"The ER\u03b1-NRF2 signalling axis promotes bicalutamide resistance in prostate cancer","volume":"20","author":"Tian","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"163","DOI":"10.4062\/biomolther.2019.071","article-title":"Involvement of Estrogen Receptor-\u03b1 in the Activation of Nrf2-Antioxidative Signaling Pathways by Silibinin in Pancreatic \u03b2-Cells","volume":"28","author":"Chu","year":"2020","journal-title":"Biomol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhao, H., You, X., Chen, Q., Yang, S., Ma, Q., He, Y., Liu, C., Dun, Y., Wu, J., and Zhang, C. (2020). Icariin Improves Age-Related Testicular Dysfunction by Alleviating Sertoli Cell Injury via Upregulation of the ER\u03b1\/Nrf2-Signaling Pathway. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00677"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"173236","DOI":"10.1016\/j.ejphar.2020.173236","article-title":"Silychristin A activates Nrf2-HO-1\/SOD2 pathway to reduce apoptosis and improve GLP-1 production through upregulation of estrogen receptor \u03b1 in GLUTag cells","volume":"881","author":"Wang","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kim, J.-H., Im, E., Lee, J., Lee, H.-J., Sim, D.Y., Park, J.E., Ahn, C.-H., Kwon, H.H., Shim, B.S., and Kim, B. (2022). Apoptotic and DNA Damage Effect of 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose in Cisplatin-Resistant Non-Small Lung Cancer Cells via Phosphorylation of H2AX, CHK2 and p53. Cells, 11.","DOI":"10.3390\/cells11081343"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1142\/S0192415X19500356","article-title":"\u03b2-Pentagalloyl-Glucose Sabotages Pancreatic Cancer Cells and Ameliorates Cachexia in Tumor-Bearing Mice","volume":"47","author":"Yang","year":"2019","journal-title":"Am. J. Chin. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/S0006-2952(03)00156-4","article-title":"Induction of G1 phase arrest in MCF human breast cancer cells by pentagalloylglucose through the down-regulation of CDK4 and CDK2 activities and up-regulation of the CDK inhibitors p27Kip and p21Cip","volume":"65","author":"Chen","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/mc.20226","article-title":"Pentagalloylglucose inhibits estrogen receptor \u03b1 by lysosome-dependent depletion and modulates ErbB\/PI3K\/Akt pathway in human breast cancer MCF-7 cells","volume":"45","author":"Hua","year":"2006","journal-title":"Mol. Carcinog."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Cheng, S., Xin, Z., Deng, H., Wang, Y., Li, Q., Wu, G., and Chen, W. (2022). 1,2,3,4,6-O-Pentagalloylglucose Protects against Acute Lung Injury by Activating the AMPK\/PI3K\/Akt\/Nrf2 Pathway. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214423"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1111\/bph.14583","article-title":"1,2,3,4,6-Penta-O-galloyl-\u03b2-d-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension","volume":"176","author":"Mikolajczyk","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"639","DOI":"10.3892\/etm.2022.11576","article-title":"1,2,3,4,6-penta-O-galloyl-\u03b2-D-glucose alleviates inflammation and oxidative stress in diabetic nephropathy rats through MAPK\/NF-\u03baB and ERK\/Nrf2\/HO-1 signaling pathways","volume":"24","author":"Wang","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jphs.2021.08.006","article-title":"Pentagalloylglucose reduces AGE-induced inflammation by activating Nrf2\/HO-1 and inhibiting the JAK2\/STAT3 pathway in mesangial cells","volume":"147","author":"Tong","year":"2021","journal-title":"J. Pharmacol. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13291","DOI":"10.1074\/jbc.R900010200","article-title":"The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress","volume":"284","author":"Nguyen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1200\/JCO.20.03565","article-title":"Next-generation endocrine therapies for breast cancer","volume":"39","author":"McDonnell","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e244","DOI":"10.1002\/mco2.244","article-title":"Mechanistic advances in osteoporosis and anti-osteoporosis therapies","volume":"4","author":"Wang","year":"2023","journal-title":"MedComm"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jsbmb.2013.12.011","article-title":"Use of SERMs for treatment in postmenopausal women","volume":"142","author":"Pinkerton","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e2303494","DOI":"10.1002\/smll.202303494","article-title":"Bone-Targeted Biomimetic Nanogels Re-Establish Osteoblast\/Osteoclast Balance to Treat Postmenopausal Osteoporosis","volume":"20","author":"Cui","year":"2024","journal-title":"Small"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1152\/physrev.00033.2015","article-title":"Estrogens and Androgens in Skeletal Physiology and Pathophysiology","volume":"97","author":"Almeida","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"101855","DOI":"10.1016\/j.beem.2023.101855","article-title":"Menopause: Physiology, definitions, and symptoms","volume":"38","author":"Gatenby","year":"2024","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/s41401-022-01006-1","article-title":"Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS\/AMPK signaling pathway","volume":"44","author":"Song","year":"2023","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7032","DOI":"10.7150\/thno.74197","article-title":"TCA-phospholipid-glycolysis targeted triple therapy effectively suppresses ATP production and tumor growth in glioblastoma","volume":"12","author":"Yang","year":"2022","journal-title":"Theranostics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"154729","DOI":"10.1016\/j.phymed.2023.154729","article-title":"Loureirin C inhibits ferroptosis after cerebral ischemia reperfusion through regulation of the Nrf2 pathway in mice","volume":"113","author":"Liu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_83","unstructured":"(2021). Technical Requirements for Breeding Laboratory Zebrafish (Standard No. DB32\/T3979-2021)."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41467-019-14169-z","article-title":"Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1\/TFEB pathway","volume":"11","author":"Sun","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"163783","DOI":"10.1016\/j.scitotenv.2023.163783","article-title":"Toxic effects of triphenyltin on the development of zebrafish (Danio rerio) embryos","volume":"885","author":"Qiao","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1039\/D2FO02788G","article-title":"Protective effects of Lycium barbarum L. berry extracts against oxidative stress-induced damage of the retina of aging mouse and ARPE-19 cells","volume":"14","author":"Zheng","year":"2023","journal-title":"Food Funct."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e37020","DOI":"10.1016\/j.heliyon.2024.e37020","article-title":"The hemostatic molecular mechanism of Sanguisorbae Radix\u2019s pharmacological active components based on HSA: Spectroscopic investigations, molecular docking and dynamics simulation","volume":"10","author":"Xu","year":"2024","journal-title":"Heliyon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.1080\/07391102.2019.1699862","article-title":"Design potential selective inhibitors for human leukocyte common antigen-related (PTP-LAR) with fragment replace approach","volume":"38","author":"Wu","year":"2020","journal-title":"J. Biomol. Struct. Dyn."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/21\/5110\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:23:28Z","timestamp":1760113408000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/21\/5110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,29]]},"references-count":88,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["molecules29215110"],"URL":"https:\/\/doi.org\/10.3390\/molecules29215110","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,29]]}}}