{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:56Z","timestamp":1787027516053,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["FF082\/2567"],"award-info":[{"award-number":["FF082\/2567"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["RG32\/2567"],"award-info":[{"award-number":["RG32\/2567"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002842","name":"Research Center for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai, Thailand","doi-asserted-by":"publisher","award":["FF082\/2567"],"award-info":[{"award-number":["FF082\/2567"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002842","name":"Research Center for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai, Thailand","doi-asserted-by":"publisher","award":["RG32\/2567"],"award-info":[{"award-number":["RG32\/2567"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Perilla seed meal (PSM) is a waste biomass of perilla seed extraction that retains flavonoid and phenolic compounds. In this study, we aimed to investigate the potential of PSM extracts (PSMEs) from Perilla frutescens (L.) Britton as a sustainable source of natural active pharmaceutical ingredients (NAPIs) containing rosmarinic acid and luteolin for promoting bone health. PSMEs were obtained through shaking incubation and ultrasonic extraction, with 40% ethanol (PS-E40) and 80% ethanol (PS-E80) being found to be the most effective solvents. The effects of PSMEs on bone formation markers were evaluated in human fetal osteoblast cells (hFOB 1.19) using bone formation parameters. The results demonstrated that PS-E40 and PS-E80 extracts significantly increased alkaline phosphatase (ALP) activity, osteocalcin (OC) production, and osteoprotegerin (OPG) levels while concurrently reducing receptor activator of nuclear factor kappa-\u0392 ligand (RANKL) and reactive oxygen species (ROS) production in a dose-dependent manner, particularly at 100 \u00b5g\/mL on day 7 and 50 and 100 \u00b5g\/mL on day 14 of the co-incubation period. Moreover, Alizarin Red S staining demonstrated that PS-E40 enhanced calcium deposition in both normal and osteogenic media, further supporting the effect of PSMEs on mineralization and osteoblast differentiation. Our findings suggest that PSMEs rich in rosmarinic acid and luteolin enhance bone health by promoting osteoblast activity and reducing osteoclastogenesis.<\/jats:p>","DOI":"10.3390\/antiox14080973","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T11:41:53Z","timestamp":1754653313000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Perilla Seed Meal Extract Enriched with Rosmarinic Acid and Luteolin: Natural Active Pharmaceutical Ingredients (NAPIs) for Osteoprotective Effects"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-5875","authenticated-orcid":false,"given":"Thanawat","family":"Pattananandecha","sequence":"first","affiliation":[{"name":"Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Research Center for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutasinee","family":"Apichai","sequence":"additional","affiliation":[{"name":"Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Research Center for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-6444","authenticated-orcid":false,"given":"Treethip","family":"Sukkho","sequence":"additional","affiliation":[{"name":"Research Center for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9891-8113","authenticated-orcid":false,"given":"Jetsada","family":"Ruangsuriya","sequence":"additional","affiliation":[{"name":"Research Center for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2755-8341","authenticated-orcid":false,"given":"Fumihiko","family":"Ogata","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9412-0868","authenticated-orcid":false,"given":"Naohito","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan"},{"name":"Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0229-5116","authenticated-orcid":false,"given":"Chalermpong","family":"Saenjum","sequence":"additional","affiliation":[{"name":"Research Center for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"ref_1","first-page":"17455057231176655","article-title":"An overview of the management of osteoporosis in the aging female population","volume":"19","author":"Amin","year":"2023","journal-title":"Women\u2019s Health"},{"key":"ref_2","first-page":"46","article-title":"An overview and management of osteoporosis","volume":"4","year":"2017","journal-title":"Eur. J. Rheumatol. Inflamm."},{"key":"ref_3","first-page":"2845","article-title":"Understanding osteoporosis: A comprehensive review of risk factors, mechanisms, and management strategies","volume":"12","author":"Sivakumar","year":"2024","journal-title":"Int. J. Intell. Syst. Appl. Eng."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.afos.2023.05.002","article-title":"Current issues in evaluation and management of osteoporosis in Thailand","volume":"9","author":"Charoenngam","year":"2023","journal-title":"Osteopor. Sarcopenia"},{"key":"ref_5","first-page":"154","article-title":"Economic burden of osteoporosis in the world: A systematic review","volume":"34","author":"Rezapour","year":"2020","journal-title":"Med. J. Islam. Repub. Iran."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/bcp.13759","article-title":"Side effects of drugs for osteoporosis and metastatic bone disease","volume":"85","author":"Frost","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, S.-S., He, S.-H., Xie, P.-Y., Li, W., Zhang, X.-X., Li, T.-F., and Li, D.-F. (2021). Recent progresses in the treatment of osteoporosis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.717065"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e3211","DOI":"10.1136\/bmj.e3211","article-title":"Bisphosphonates in the treatment of osteoporosis","volume":"344","author":"Poole","year":"2012","journal-title":"Br. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/bcp.12033","article-title":"Phytonutrients for bone health during ageing","volume":"75","author":"Sacco","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hanga-Farca\u0219, A., Miere, F., Filip, G.A., Clichici, S., Fritea, L., Vica\u0219, L.G., Marian, E., Pallag, A., Jurca, T., and Filip, S.M. (2023). Phytochemical compounds involved in the bone regeneration process and their innovative administration: A systematic review. Plants, 12.","DOI":"10.20944\/preprints202304.0484.v1"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1186\/s13018-023-04448-3","article-title":"Prevention and treatment of osteoporosis with natural products: Regulatory mechanism based on cell ferroptosis","volume":"18","author":"Yang","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_13","first-page":"e2021074","article-title":"The Attenuation of TNF-\u03b1-mediated Inflammatory Responses in Human Lung Adenocarcinoma Cell Line by Perilla Seed and Seed Meal Extract","volume":"20","author":"Khanaree","year":"2021","journal-title":"Chiang Mai Univ. J. Nat. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s12231-017-9383-1","article-title":"Phenotypic and genetic diversity of local Perilla (Perilla frutescens (L.) Britt.) from northern Thailand","volume":"71","author":"Pusadee","year":"2017","journal-title":"Econ. Bot."},{"key":"ref_15","first-page":"112","article-title":"Thai perilla (Perilla frutescens) leaf extract inhibits human breast cancer invasion and migration","volume":"12","author":"Pintha","year":"2018","journal-title":"Maejo Int. J. Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ahmed, H.M. (2019). Ethnomedicinal, phytochemical and pharmacological investigations of Perilla frutescens (L.) Britt. Molecules, 24.","DOI":"10.3390\/molecules24010102"},{"key":"ref_17","first-page":"369","article-title":"Perilla frutescens: A traditional medicine and food homologous plant","volume":"15","author":"Wu","year":"2023","journal-title":"Chin. Herb. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, H., Lin, J., Bai, B., Bo, T., He, Y., Fan, S., and Zhang, J. (2023). Study on purification, identification, and antioxidant of flavonoids extracted from Perilla leaves. Molecules, 28.","DOI":"10.3390\/molecules28217273"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hou, T., Netala, V.R., Zhang, H., Xing, Y., Li, H., and Zhang, Z. (2022). Perilla frutescens: A rich source of pharmacological active compounds. Molecules, 27.","DOI":"10.3390\/molecules27113578"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/pca.2521","article-title":"Identification and quantitation of phenolic compounds from the seed and pomace of perilla frutescens using HPLC\/PDA and HPLC-ESI\/QTOF\/MS\/MS","volume":"25","author":"Guan","year":"2014","journal-title":"Phytochem. Anal."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Adam, G., Robu, S., Flutur, M.M., Cioanca, O., Vasilache, I.A., Adam, A.M., Mircea, C., Nechita, A., Harabor, V., and Harabor, A. (2023). Applications of Perilla frutescens extracts in clinical practice. Antioxidants, 12.","DOI":"10.3390\/antiox12030727"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Khojasteh, A., Mirjalili, M.H., Alcalde, M.A., Cusido, R.M., Eibl, R., and Palazon, J. (2020). Powerful Plant Antioxidants: A New Biosustainable Approach to the Production of Rosmarinic Acid. Antioxidants, 9.","DOI":"10.3390\/antiox9121273"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Guan, H., Luo, W., Bao, B., Cao, Y., Cheng, F., Yu, S., Fan, Q., Zhang, L., Wu, Q., and Shan, M. (2022). A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight. Molecules, 27.","DOI":"10.3390\/molecules27103292"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Punia Bangar, S., Kajla, P., Chaudhary, V., Sharma, N., and Ozogul, F. (2023). Luteolin: A flavone with myriads of bioactivities and food applications. Food Biosci., 52.","DOI":"10.1016\/j.fbio.2023.102366"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Phromnoi, K., Suttajit, M., Saenjum, C., and Limtrakul, P. (2021). Inhibitory Effect of a Rosmarinic Acid-Enriched Fraction Prepared from Nga-Mon (Perilla frutescens) Seed Meal on Osteoclastogenesis through the RANK Signaling Pathway. Antioxidants, 10.","DOI":"10.3390\/antiox10020307"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Phromnoi, K., Yodkeeree, S., Pintha, K., Mapoung, S., Suttajit, M., Saenjum, C., and Dejkriengkraikul, P. (2022). Anti-osteoporosis effect of Perilla frutescens leaf hexane fraction through regulating osteoclast and osteoblast differentiation. Molecules, 27.","DOI":"10.3390\/molecules27030824"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"846","DOI":"10.4103\/2230-8210.192914","article-title":"Bone turnover markers: Emerging tool in the management of osteoporosis","volume":"20","author":"Shetty","year":"2016","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Huang, S., Nan, Y., Chen, G., Ning, N., Du, Y., Lu, D., Yang, Y., Meng, F., and Yuan, L. (2023). The role and mechanism of Perilla frutescens in cancer treatment. Molecules, 28.","DOI":"10.3390\/molecules28155883"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Liu, M., Ding, Y., Wang, T., Ma, Y., Huang, J., He, S., Qu, Q., Sun, F., and Lv, W. (2023). Effects of Perilla seed meal on productive performance, egg quality, antioxidant capacity, and hepatic lipid metabolism of Wenchang breeder hens. Animals, 13.","DOI":"10.3390\/ani13223587"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1002\/fsn3.998","article-title":"Purification and identification of an antioxidant peptide from perilla seed (Perilla frutescens) meal protein hydrolysate","volume":"7","author":"Kim","year":"2019","journal-title":"Food Sci. Nutr."},{"key":"ref_31","first-page":"130","article-title":"Studies on the extraction of polyphenolic compounds from pre-consumer organic solid waste","volume":"82","author":"Sivashanmugam","year":"2019","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Oroian, M., Ursachi, F., and Dranca, F. (2020). Ultrasound-assisted extraction of polyphenols from crude pollen. Antioxidants, 9.","DOI":"10.3390\/antiox9040322"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pattananandecha, T., Apichai, S., Julsrigival, J., Ungsurungsie, M., Samuhasaneetoo, S., Chulasiri, P., Kwankhao, P., Pitiporn, S., Ogata, F., and Kawasaki, N. (2021). Antioxidant activity and anti-photoaging effects on UVA-irradiated human fibroblasts of rosmarinic acid enriched extract prepared from Thunbergia laurifolia leaves. Plants, 10.","DOI":"10.3390\/plants10081648"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sukkho, T., Khanongnuch, C., Lumyong, S., Ruangsuriya, J., Pattananandecha, T., Apichai, S., Ogata, F., Kawasaki, N., and Saenjum, C. (2022). Local wisdom and diversity of medicinal plants in Cha Miang Forest in Mae Kampong Village, Chiang Mai, Thailand, and their potential for use as osteoprotective products. Plants, 11.","DOI":"10.3390\/plants11111492"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bernar, A., Gebetsberger, J.V., Bauer, M., Streif, W., and Schirmer, M. (2023). Optimization of the alizarin red s assay by enhancing mineralization of osteoblasts. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010723"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.3390\/molecules15107313","article-title":"Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties","volume":"15","author":"Dai","year":"2010","journal-title":"Molecules"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Fern\u00e1ndez, O., Dom\u00ednguez, R., Pateiro, M., Munekata, P.E.S., Rocchetti, G., and Lorenzo, J.M. (2020). Determination of polyphenols using liquid chromatography-tandem mass spectrometry technique (LC-MS\/MS): A review. Antioxidants, 9.","DOI":"10.3390\/antiox9060479"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lau, C.H., and Chua, L.S. (2019). Solubility models for the recovery of rosmarinic acid from Orthosiphon aristatus extract using solid phase extraction. Chem. Eng., 3.","DOI":"10.3390\/chemengineering3030064"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Elmowafy, M., Shalaby, K., Al-Sanea, M.M., Hendawy, O.M., Salama, A., Ibrahim, M.F., and Ghoneim, M.M. (2021). Influence of stabilizer on the development of luteolin nanosuspension for cutaneous delivery: An in vitro and in vivo evaluation. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111812"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s12272-022-01378-2","article-title":"Biomedical features and therapeutic potential of rosmarinic acid","volume":"45","author":"Noor","year":"2022","journal-title":"Arch. Pharm. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115576","DOI":"10.1016\/j.fct.2025.115576","article-title":"Protective effects of rosmarinic acid against oxidative damage and atherosclerosis via the PI3K\/AKT pathway","volume":"203","author":"Tang","year":"2025","journal-title":"Food Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3892\/mmr.2024.13244","article-title":"Protective effect of luteolin against oxidative stress-mediated cell injury via enhancing antioxidant systems","volume":"30","author":"Fernando","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e4682","DOI":"10.1002\/fsn3.4682","article-title":"Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies","volume":"13","author":"Mahwish","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jobcr.2020.04.006","article-title":"A quantitative method to determine osteogenic differentiation aptness of scaffold","volume":"10","author":"Trivedi","year":"2020","journal-title":"J. Oral Biol. Craniofacial Res."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1097\/BCO.0b013e3282630851","article-title":"The role of alkaline phosphatase in mineralization","volume":"18","author":"Golub","year":"2007","journal-title":"Curr. Opin. Orthop."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/mnfr.201400164","article-title":"Rosmarinic acid exerts an antiosteoporotic effect in the RANKL-induced mouse model of bone loss by promotion of osteoblastic differentiation and inhibition of osteoclastic differentiation","volume":"59","author":"Lee","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1080\/19768354.2021.1886987","article-title":"Effect of rosmarinic acid on differentiation and mineralization of MC3T3-E1 osteoblastic cells on titanium surface","volume":"25","author":"Jeong","year":"2021","journal-title":"Anim. Cells Syst."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.cellbi.2007.01.038","article-title":"Modulatory effects of luteolin on osteoblastic function and inflammatory mediators in osteoblastic MC3T3-E1 cells","volume":"31","author":"Choi","year":"2007","journal-title":"Cell Biol. Int."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Quan, H., Dai, X., Liu, M., Wu, C., and Wang, D. (2019). Luteolin supports osteogenic differentiation of human periodontal ligament cells. BMC Oral Health, 19.","DOI":"10.1186\/s12903-019-0926-y"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1089\/ten.tec.2007.0334","article-title":"Osteocalcin secretion as an early marker of in vitro osteogenic differentiation of rat mesenchymal stem cells","volume":"15","author":"Nakamura","year":"2009","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bone.2015.05.046","article-title":"New insights into the biology of osteocalcin","volume":"82","author":"Zoch","year":"2016","journal-title":"Bone"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"115031","DOI":"10.1016\/j.bone.2019.08.004","article-title":"Osteocalcin affects bone mineral and mechanical properties in female mice","volume":"128","author":"Berezovska","year":"2019","journal-title":"Bone"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.abb.2008.03.018","article-title":"Functions of RANKL\/RANK\/OPG in bone modeling and remodeling","volume":"473","author":"Boyce","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kitaura, H., Marahleh, A., Ohori, F., Noguchi, T., Shen, W.-R., Qi, J., Nara, Y., Pramusita, A., Kinjo, R., and Mizoguchi, I. (2020). Osteocyte-related cytokines regulate osteoclast formation and bone resorption. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145169"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.2147\/CMAR.S431213","article-title":"Osteoclasts in osteosarcoma: Mechanisms, interactions, and therapeutic prospects","volume":"15","author":"Gao","year":"2023","journal-title":"Cancer Manag. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s10616-010-9253-5","article-title":"Inhibitory effect of luteolin on osteoclast differentiation and function","volume":"61","author":"Lee","year":"2009","journal-title":"Cytotechnology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1002\/JPER.18-0584","article-title":"The effect of luteolin in prevention of periodontal disease in Wistar rats","volume":"90","author":"Toker","year":"2019","journal-title":"J. Periodontol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/8\/973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:26:24Z","timestamp":1760034384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/8\/973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":58,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["antiox14080973"],"URL":"https:\/\/doi.org\/10.3390\/antiox14080973","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]}}}