{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T05:05:07Z","timestamp":1780031107703,"version":"3.53.1"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Central nervous system disorders (CNSDs) are a leading cause of global mortality and disability, yet treatment options remain limited. Natural compounds derived from traditional Chinese herbs constitute a vital resource for discovering novel neuroprotective agents. Atractylenolide III (ATL-III), a sesquiterpene lactone isolated from the spleen-fortifying herb\n                    <jats:italic>Atractylodes macrocephala<\/jats:italic>\n                    Koidz., exhibits neuroprotective properties and possesses the ability to cross the blood-brain barrier (BBB). However, a systematic summary of its effects on CNSDs is currently lacking. This review therefore aimed to comprehensively summarize the therapeutic effects and underlying mechanisms of ATL-III against various CNSDs, and to provide insights for future clinical translation. A systematic literature search was conducted using PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang Database for studies published or available online between 1 January 2016, and 31 December 2025. The compiled evidence demonstrates that ATL-III is effective in preclinical models of cognitive impairment, cerebral ischemia\/reperfusion injury, depressive disorder, and spinal cord injury. Its neuroprotective mechanisms are multifaceted, involving the enhancement of neurotransmitter storage, reduction of neurotoxic protein accumulation, and exerting anti-apoptotic, anti-inflammatory, antioxidant, and autophagy-regulating effects, alongside BBB repair. In conclusion, ATL-III exerts broad neuroprotective effects through multi-target mechanisms, highlighting its promise as a therapeutic candidate for CNSDs. To realize this potential, key future efforts should include: (1) conducting definitive clinical trials to establish its efficacy and safety profile; (2) comprehensively elucidating its pharmacological and toxicological properties; and (3) developing novel delivery strategies to enhance its bioavailability, BBB penetration, and brain retention.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1799976","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:49:27Z","timestamp":1780030167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Atractylenolide III for central nervous system disorders: a review of multi-target mechanisms and therapeutic potential"],"prefix":"10.3389","volume":"17","author":[{"given":"Han","family":"Li","sequence":"first","affiliation":[{"name":"Shenzhen Bao\u2019an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]},{"name":"Shenzhen Key Laboratory of Metabolic Health, Shenzhen Metabolism and Reproductive Targeted Delivery Proof-of-Concept Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Xi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Medical Research Center, Dalang Hospital of Dongguan","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ge","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Metabolic Health, Shenzhen Metabolism and Reproductive Targeted Delivery Proof-of-Concept Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Liang","family":"Ye","sequence":"additional","affiliation":[{"name":"Medical Research Center, Dalang Hospital of Dongguan","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Yang","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Shenzhen Bao\u2019an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Na","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical Research Center, Dalang Hospital of Dongguan","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liang","sequence":"additional","affiliation":[{"name":"Shenzhen Bao\u2019an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian V.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Metabolic Health, Shenzhen Metabolism and Reproductive Targeted Delivery Proof-of-Concept Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shenzhen Bao\u2019an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"549","DOI":"10.3390\/plants11040549","article-title":"Natural products as novel neuroprotective agents; computational predictions of the molecular targets, ADME properties, and safety profile","volume":"11","author":"Alghamdi","year":"2022","journal-title":"Plants"},{"key":"B2","doi-asserted-by":"publisher","first-page":"282","DOI":"10.3389\/fneur.2019.00282","article-title":"Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms","volume":"10","author":"Alizadeh","year":"2019","journal-title":"Front. 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