Information from the abstract
Abstract Huperzine A (HupA), a sesquiterpene alkaloid isolated from Huperzia serrata, is clinically applied in China for Alzheimer’s 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’s 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 ± 8.3 nm to 253.4 ± 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 < 0.001). In vivo, MPTP-induced Parkinsonian mice receiving SEDDS containing HupA (0.75 and 1.00 μmol/kg body weight) showed significant improvements in locomotor function and motor coordination compared with both vehicle- and blank-SEDDS-treated groups (p < 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 < 0.05). Molecular studies confirmed that HupA-loaded SEDDS increased tyrosine hydroxylase and decreased tumor necrosis factor-α expression compared with the vehicle-treated group (p < 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.
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Related topics: Cholinesterase and Neurodegenerative Diseases · Advancements in Transdermal Drug Delivery · Cannabis and Cannabinoid Research
Thai researcher and institutional participation
Namfa Sermkaew · Nuttapon Songnaka · Wuttipong Masraksa · Amit Jaisi · Yosita Yongyuen · Pannatorn Buntha · Juntratip Jomrit · Phetcharat Boonruamkaew · Walailak University · Vongchavalitkul University · Chulalongkorn University
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