{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:13:04Z","timestamp":1788221584328,"version":"build-2803163510"},"reference-count":69,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"publisher","award":["Fund contract no.FF-WU68-07"],"award-info":[{"award-number":["Fund contract no.FF-WU68-07"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Huperzine A (HupA), a sesquiterpene alkaloid isolated from Huperzia serrata, is clinically applied in China for Alzheimer\u2019s disease and in the United States as a dietary supplement. In Thailand, Huperzia carinata (H. carinata) is an alternative and the richest natural source of HupA. However, poor solubility and low oral bioavailability restrict its therapeutic application. This study aimed to develop a self-emulsifying drug delivery system (SEDDS) to improve the solubility, dissolution, and efficacy of HupA from H. carinata extract in a mouse model of Parkinson\u2019s disease (PD). The optimized SEDDS consisted of oleic acid (20%), polyethylene glycol-40 hydrogenated castor oil (70%), and propylene glycol (10%), containing 10% H. carinata extract. The HupA-loaded SEDDS displayed efficient self-emulsification, producing droplet sizes of 175.2 \u00b1 8.3 nm to 253.4 \u00b1 2.8 nm upon dilution in water. The SEDDS promoted rapid dissolution, achieving approximately 70% HupA release within 5 min and near-complete dissolution (100%) by 120 min in both gastric and intestinal media. In vitro, the SEDDS displayed significantly superior antioxidant and anti-inflammatory activities compared with the unformulated extract (p &amp;lt; 0.001). In vivo, MPTP-induced Parkinsonian mice receiving SEDDS containing HupA (0.75 and 1.00 \u03bcmol\/kg body weight) showed significant improvements in locomotor function and motor coordination compared with both vehicle- and blank-SEDDS-treated groups (p &amp;lt; 0.001) at days 3 and 7 after MPTP induction. Biochemical assessments revealed declined malondialdehyde and nitrite levels in cortical and striatal brain tissues compared with the vehicle- and blank-SEDDS-treated groups (p &amp;lt; 0.05). Molecular studies confirmed that HupA-loaded SEDDS increased tyrosine hydroxylase and decreased tumor necrosis factor-\u03b1 expression compared with the vehicle-treated group (p &amp;lt; 0.001) while protecting dopaminergic neurons in immunohistochemistry, indicating neuroprotective and antineuroinflammatory effects. The SEDDS formulation may represent a promising drug delivery system for the clinical application of HupA in PD and potentially other neurodegenerative disorders. This study contributes to Sustainable Development Goal 3 (good health and well-being) by developing neuroprotective formulations for neurodegenerative diseases.<\/jats:p>","DOI":"10.1021\/acsomega.6c04075","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:13:15Z","timestamp":1785917595000},"page":"49717-49732","source":"Crossref","is-referenced-by-count":0,"title":["Self-Emulsifying\nFormulation of\n                    <i>Huperzia carinata<\/i>\n                    Extract to Improve Huperzine A Solubility\nfor Therapeutic Efficacy Enhancement in Parkinsonian Mice"],"prefix":"10.1021","volume":"11","author":[{"given":"Namfa","family":"Sermkaew","sequence":"first","affiliation":[{"name":"Walailak University , , ,","place":["Nakhon Si Thammarat, Thailand, 80160"]},{"name":"Walailak University , , ,","place":["Nakhon Si Thammarat, Thailand, 80160"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuttapon","family":"Songnaka","sequence":"additional","affiliation":[{"name":"Walailak University , , ,","place":["Nakhon Si Thammarat, Thailand, 80160"]},{"name":"Walailak University , , ,","place":["Nakhon Si Thammarat, Thailand, 80160"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0458-2091","authenticated-orcid":true,"given":"Wuttipong","family":"Masraksa","sequence":"additional","affiliation":[{"name":"Vongchavalitkul University , , ,","place":["Nakhon Ratchasima, Thailand, 30000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0261-7170","authenticated-orcid":true,"given":"Amit","family":"Jaisi","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosita","family":"Yongyuen","sequence":"additional","affiliation":[{"name":"Walailak University , , ,","place":["Nakhon Si Thammarat, Thailand, 80160"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pannatorn","family":"Buntha","sequence":"additional","affiliation":[{"name":"Walailak University , , ,","place":["Nakhon Si Thammarat, Thailand, 80160"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiah Syafiqah","family":"Nor Azman","sequence":"additional","affiliation":[{"name":"Lincoln University College , , ,","place":["Selangor, Malaysia, 47301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-8471","authenticated-orcid":true,"given":"Juntratip","family":"Jomrit","sequence":"additional","affiliation":[{"name":"Walailak University , , ,","place":["Nakhon Si Thammarat, Thailand, 80160"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0666-7522","authenticated-orcid":true,"given":"Phetcharat","family":"Boonruamkaew","sequence":"additional","affiliation":[{"name":"Walailak University , , ,","place":["Nakhon Si Thammarat, Thailand, 80160"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"2026083119135003100_cit1","doi-asserted-by":"publisher","first-page":"1498756","DOI":"10.3389\/fnagi.2024.1498756","article-title":"Global, regional, national epidemiology and trends of Parkinson\u2019s\ndisease from 1990 to 2021: findings from the Global Burden of Disease\nStudy 2021","volume":"16","author":"Luo","year":"2025","journal-title":"Front. 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Primers"},{"issue":"6","key":"2026083119135003100_cit4","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1177\/0891988719892318","article-title":"Visual Hallucinations and Impaired\nConscious Visual\nPerception in Parkinson Disease","volume":"33","author":"Kurita","year":"2020","journal-title":"J. Geriatr\nPsychiatry Neurol."},{"key":"2026083119135003100_cit5","doi-asserted-by":"publisher","first-page":"154757","DOI":"10.1016\/j.prp.2023.154757","article-title":"Involvement of antioxidant enzymes\nin Parkinson\u2019s\ndisease","volume":"249","author":"Tahavvori","year":"2023","journal-title":"Pathol Res. Pract."},{"key":"2026083119135003100_cit6","doi-asserted-by":"publisher","first-page":"8421","DOI":"10.3390\/ijms21228421","article-title":"Neurodegeneration\nand Inflammation\u2500An\nInteresting Interplay in Parkinson\u2019s Disease","volume":"21","author":"Marogianni","year":"2020","journal-title":"Int. J. Mol. 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Disord.: Drug Targets"},{"key":"2026083119135003100_cit9","unstructured":"National Center for Biotechnology Information.\n          \n          PubChem\nCompound Summary for CID 854026, Huperzine A. https:\/\/pubchem.ncbi.nlm.nih.gov\/\u00a0compound\/Huperzine-A."},{"issue":"4","key":"2026083119135003100_cit10","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1139\/v86-137","article-title":"The structures\nof huperzine A and\nB, two new alkaloids exhibiting marked anticholinesterase activity","volume":"64","author":"Liu","year":"1986","journal-title":"Can. J. Chem."},{"key":"2026083119135003100_cit11","doi-asserted-by":"publisher","first-page":"113","DOI":"10.2147\/JEP.S27084","article-title":"The pharmacology\nand therapeutic potential of (-)-huperzine\nA","volume":"4","author":"Tun","year":"2012","journal-title":"J. Exp.Pharmacol."},{"issue":"6","key":"2026083119135003100_cit12","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1007\/s11011-017-0075-4","article-title":"Huperzine\nA alleviates neuroinflammation, oxidative stress and improves cognitive\nfunction after repetitive traumatic brain injury","volume":"32","author":"Mei","year":"2017","journal-title":"Metab. Brain Dis."},{"issue":"1","key":"2026083119135003100_cit13","doi-asserted-by":"publisher","first-page":"16806","DOI":"10.1038\/s41598-021-94708-1","article-title":"AZP2006, a new promising treatment for Alzheimer\u2019s\nand related diseases","volume":"11","author":"Callizot","year":"2021","journal-title":"Sci. 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Sci."},{"issue":"1","key":"2026083119135003100_cit44","first-page":"95","article-title":"Huperzine induces alteration in oxidative balance and\nantioxidants in a guinea pig model","volume":"32","author":"Pohanka","year":"2011","journal-title":"Neuro Endocrinol.\nLett."},{"issue":"1","key":"2026083119135003100_cit45","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1080\/10717544.2020.1797240","article-title":"Dissolving microneedles for transdermal\ndelivery of huperzine A for the treatment of Alzheimer\u2019s disease","volume":"27","author":"Yan","year":"2020","journal-title":"Drug Delivery"},{"issue":"6","key":"2026083119135003100_cit46","doi-asserted-by":"publisher","first-page":"752","DOI":"10.3109\/03639045.2011.625031","article-title":"Microemulsion-based\npatch for transdermal delivery of huperzine A and ligustrazine phosphate\nin treatment of Alzheimer\u2019s disease","volume":"38","author":"Shi","year":"2012","journal-title":"Drug Dev. Ind. 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