{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:49:44Z","timestamp":1785408584914,"version":"3.56.0"},"reference-count":99,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Fund 2025","award":["207556"],"award-info":[{"award-number":["207556"]}]},{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05m2fqn25","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"crossref","award":["FRB680102\/0162"],"award-info":[{"award-number":["FRB680102\/0162"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FRB680102\/0162"],"award-info":[{"award-number":["FRB680102\/0162"]}],"id":[{"id":"https:\/\/ror.org\/000025p04","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The prevalent endocrine disruptor bisphenol A (BPA) is associated with aging-related conditions, including metabolic disorders. It has been shown that BPA promotes bone fragility through oxidative stress-induced apoptosis and impaired osteoblast differentiation. The identification of sustainable bioactive substances that alleviate BPA-induced bone toxicity is thus of biomedical and environmental significance. Wolffia globosa (WG), the world\u2019s smallest flowering aquatic plant, has recently gained attention as a high-protein, antioxidant-rich nutraceutical, yet its impact on BPA-induced osteoblast dysfunction has not been systematically investigated. This study presents a comprehensive assessment of WG ethanolic extract (WGE) in MC3T3-E1 pre-osteoblasts, incorporating thorough phytochemical characterization, acute high-dose and chronic low-dose BPA exposure models, and multi-faceted mechanistic analysis. LC-MS\/MS profiling identified luteolin (116.17 \u00b1 0.69 \u00b5g\/g), rosmarinic acid (54.80 \u00b1 2.12 \u00b5g\/g), and apigenin (48.77 \u00b1 0.61 \u00b5g\/g) as the predominant bioactive compounds. WGE exhibited potent antioxidant capacity across DPPH and ABTS radical scavenging assays, complemented by high ORAC and FRAP values, reflecting broad-spectrum antioxidant mechanisms. Treatment with WGE (25 and 50 \u00b5g\/mL) resulted in significant alleviation of BPA-induced cytotoxicity, decreased intracellular ROS levels, and inhibited apoptosis. WGE (12.5 \u00b5g\/mL) also modulated autophagy-related markers (LC3-II, Beclin-1, and p62), suggesting potential autophagic participation, although flux verification was not conducted. Treatment with WGE (12.5 \u00b5g\/mL) also restored BPA-suppressed osteogenesis under chronic exposure, as evidenced by enhanced alkaline phosphatase activity, and increased both mineralization and upregulation of osteogenic genes including runt-related transcription factor2 (Runx2), collagen type I alpha 1 (Colla1), alkaline phosphatase (ALP), and osteocalcin (OCN). These effects were accompanied by partial reactivation of Wnt\/\u03b2-catenin signaling. This study is the first to demonstrate that WGE protects osteoblasts from BPA toxicity by concurrently strengthening antioxidant defenses, limiting apoptosis, modulating autophagy-related markers, and supporting \u03b2-catenin-mediated osteogenesis, highlighting WG as a promising sustainable nutraceutical candidate for the prevention of environmental toxin-related bone fragility.<\/jats:p>","DOI":"10.3390\/ijms27125352","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:57:58Z","timestamp":1781513878000},"page":"5352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Wolffia globosa Ethanolic Extract Protects Against Bisphenol A-Induced Osteoblast Dysfunction via Antioxidant Defense, Apoptosis Inhibition, and \u03b2-Catenin Modulation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4383-4410","authenticated-orcid":false,"given":"Benjawan","family":"Wudtiwai","sequence":"first","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-386X","authenticated-orcid":false,"given":"Pornsiri","family":"Pitchakarn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-7024","authenticated-orcid":false,"given":"Piya","family":"Temviriyanukul","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattaralawan","family":"Sittiju","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai 50200, Thailand"},{"name":"Division of Clinical Chemistry, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4282-4908","authenticated-orcid":false,"given":"Woorawee","family":"Inthachat","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jirarat","family":"Karinchai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai 50200, Thailand"},{"name":"Faculty of Pharmacy, Institute of Entrepreneurial Science Ayutthaya, Phra Nakhon Si Ayutthaya 13000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuttida","family":"Phunsanit","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5963-2796","authenticated-orcid":false,"given":"Prachya","family":"Kongtawelert","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peraphan","family":"Pothacharoen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115330","DOI":"10.1016\/j.bone.2020.115330","article-title":"Practical guidance for the use of bisphosphonates in osteoporosis","volume":"136","author":"Compston","year":"2020","journal-title":"Bone"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115998","DOI":"10.1016\/j.bone.2021.115998","article-title":"Suppression of cancer-associated bone loss through dynamic mechanical loading","volume":"150","author":"Pagnotti","year":"2021","journal-title":"Bone"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114980","DOI":"10.1016\/j.envpol.2020.114980","article-title":"Microplastics as pollutants in agricultural soils","volume":"265","author":"Kumar","year":"2020","journal-title":"Environ. 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