Atractylenolide III shows neuroprotective effects in preclinical CNS disorder models

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Frontiers in Medicine Published May 29, 2026 Medically reviewed May 29, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider Atractylenolide III as an investigational neuroprotective agent; clinical data are absent.

This narrative review synthesizes preclinical evidence on the neuroprotective effects of Atractylenolide III, a natural compound, across several central nervous system disorders (CNSDs). The review covers studies in models of cognitive impairment, cerebral ischemia/reperfusion injury, depressive disorder, and spinal cord injury. The authors report that Atractylenolide III is effective in these preclinical models, suggesting potential as a therapeutic candidate. However, they emphasize that a systematic summary of its effects on CNSDs is currently lacking. The review does not report specific effect sizes, sample sizes, or safety data, and the authors caution that clinical efficacy, safety profile, pharmacological and toxicological properties, bioavailability, blood-brain barrier penetration, and brain retention remain uncharacterized. While the findings highlight promise, the evidence is limited to preclinical models, and no conclusions can be drawn about human application. Clinicians should interpret these results as preliminary and await further translational research.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

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 Atractylodes macrocephala 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.