{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:15:56Z","timestamp":1792815356598,"version":"4.5.0"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ligustilide (LIG), a natural phthalide compound mainly isolated from Angelica sinensis and Ligusticum chuanxiong, has attracted increasing attention because of its diverse pharmacological activities, including anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective effects. Emerging studies suggest that LIG may have therapeutic relevance in central nervous system (CNS) disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This review systematically summarizes the pharmacological effects, molecular mechanisms, pharmacokinetic characteristics, metabolism, safety profile, and therapeutic potential of LIG in CNS disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Relevant studies published up to 26 October 2025 were retrieved from PubMed, Web of Science, and Scopus using keywords related to ligustilide, central nervous system disorders, pharmacokinetics, metabolism, and toxicity. After removing duplicate records and excluding reviews, editorials, and irrelevant articles, 55 eligible original studies were included in this review.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Current evidence indicates that LIG exerts neuroprotective effects in multiple CNS disorders, including ischemic stroke, cerebral ischemia\u2013reperfusion injury, vascular dementia, Alzheimer\u2019s disease, Parkinson\u2019s disease, traumatic brain injury, and anxiety disorders. Its mechanisms mainly involve modulation of PI3K\/Akt, MAPK, NF-\u03baB, Nrf2\/ARE, AMPK, and other signaling pathways, leading to reduced oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. In addition, available studies suggest that LIG can cross the blood\u2013brain barrier and shows relatively favorable safety in preclinical models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LIG demonstrates broad neuroprotective potential in preclinical studies and may represent a promising candidate for CNS disease intervention. However, its poor chemical stability, low oral bioavailability, limited toxicity evaluation, and lack of clinical evidence remain major challenges for translational application. Further studies are required to optimize delivery strategies and validate its efficacy and safety in clinical settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1843537","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:39:43Z","timestamp":1782106783000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The latest research progress of ligustilide in the prevention and treatment of central nervous system disorders"],"prefix":"10.3389","volume":"17","author":[{"given":"Jin","family":"Han","sequence":"first","affiliation":[{"name":"Encephalopathy Center, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical School of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Sun","sequence":"additional","affiliation":[{"name":"Encephalopathy Center, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Song","sequence":"additional","affiliation":[{"name":"Encephalopathy Center, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical School of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Wu","sequence":"additional","affiliation":[{"name":"Encephalopathy Center, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical School of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Encephalopathy Center, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine","place":["Zhengzhou, China"]},{"name":"Institute of Encephalopathy, Henan Academy of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1666207","DOI":"10.3389\/fphar.2025.1666207","article-title":"Preclinical evidence and mechanistic insights of ligustilide in ischemic stroke: a systematic review and meta-analysis","volume":"16","author":"An","year":"2025","journal-title":"Front. 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