{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:02:07Z","timestamp":1784858527409,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Acute kidney injury (AKI) is a major global health challenge associated with substantial morbidity, mortality, and progression to chronic kidney disease. Increasing evidence indicates that oxidative stress, mitochondrial dysfunction, inflammatory signaling, regulated cell death, and maladaptive tissue repair play central roles in AKI pathogenesis, yet effective disease-modifying pharmacological therapies remain unavailable. This narrative review critically evaluated current evidence regarding the pharmacological characteristics, molecular mechanisms, and translational potential of alpha-mangostin (AM), the principal prenylated xanthone isolated from the pericarp of Garcinia mangostana L., through a comprehensive synthesis of experimental and mechanistic studies. Available preclinical evidence consistently demonstrates that AM improves renal function and attenuates histopathological injury, particularly in cisplatin-induced nephrotoxicity and glycerol-induced rhabdomyolysis models. These renoprotective effects are primarily associated with suppression of oxidative stress, activation of the Nrf2\/HO-1 antioxidant pathway, inhibition of NF-\u03baB-mediated inflammatory signaling, preservation of mitochondrial function, and attenuation of apoptosis. Several emerging pathways may also contribute to AM-mediated renoprotective effects; however, current evidence remains indirect, and their roles require validation in kidney-specific models. Clinical translation remains limited by poor oral bioavailability, insufficient pharmacokinetic data, lack of standardized formulations, and the absence of human clinical trials. Overall, current evidence suggests that AM has preliminary renoprotective potential in experimental AKI models. However, the limited number of available studies, predominance of cisplatin-induced nephrotoxicity models, insufficient pharmacokinetic and safety data, and absence of human clinical studies preclude conclusions regarding its clinical efficacy or translational readiness. Further validation in diverse and clinically relevant AKI models is required before clinical investigation can be considered.<\/jats:p>","DOI":"10.3390\/antiox15080915","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:18:51Z","timestamp":1784855931000},"page":"915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alpha-Mangostin in Acute Kidney Injury: Molecular Mechanisms, Regulated Cell Death, and Translational Opportunities"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-2644","authenticated-orcid":false,"given":"Atthaphong","family":"Phongphithakchai","sequence":"first","affiliation":[{"name":"Nephrology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8706-8881","authenticated-orcid":false,"given":"Nawanwat C.","family":"Pattaranggoon","sequence":"additional","affiliation":[{"name":"School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kraiyasak","family":"Wongna","sequence":"additional","affiliation":[{"name":"School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5418-8540","authenticated-orcid":false,"given":"Ratana","family":"Netphakdee","sequence":"additional","affiliation":[{"name":"School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman","family":"Tedasen","sequence":"additional","affiliation":[{"name":"School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products, Walailak University, Tha Sala, Nakhon Si Thammarat 80161, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7892-4436","authenticated-orcid":false,"given":"Chutima","family":"Jansakun","sequence":"additional","affiliation":[{"name":"School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5247-166X","authenticated-orcid":false,"given":"Wiyada Kwanhian","family":"Klangbud","sequence":"additional","affiliation":[{"name":"Medical Technology Program, Faculty of Science, Nakhon Phanom University, Nakhon Phanom 48000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4542-8980","authenticated-orcid":false,"given":"Jongkonnee","family":"Thanasai","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Mahasarakham University, Mahasarakham 44000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-2516","authenticated-orcid":false,"given":"Fumitaka","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Japan"},{"name":"Department of Health Administration, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-1155","authenticated-orcid":false,"given":"Moragot","family":"Chatatikun","sequence":"additional","affiliation":[{"name":"School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products, Walailak University, Tha Sala, Nakhon Si Thammarat 80161, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. 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