Publication: Utilizing ADMET Analysis and Molecular Docking to Elucidate the Neuroprotective Mechanisms of a Cannabis-Containing Herbal Remedy (Suk-Saiyasna) in Inhibiting Acetylcholinesterase
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Issued Date
2025-04-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-105002325771
Pubmed ID
40243991
Journal Title
International Journal of Molecular Sciences
Volume
26
Issue
7
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.26 No.7 (2025)
Suggested Citation
Sumontri S., Eiamart W., Tadtong S., Samee W. Utilizing ADMET Analysis and Molecular Docking to Elucidate the Neuroprotective Mechanisms of a Cannabis-Containing Herbal Remedy (Suk-Saiyasna) in Inhibiting Acetylcholinesterase. International Journal of Molecular Sciences Vol.26 No.7 (2025). doi:10.3390/ijms26073189 Retrieved from: https://hdl.handle.net/20.500.14740/20634
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Abstract
Alzheimer’s disease is characterized by the degeneration of cholinergic neurons, which is primarily driven by the acetylcholinesterase (AChE) enzyme and oxidative stress. This study investigated the therapeutic potential of the cannabis-containing herbal remedy Suk-Saiyasna in alleviating amyloid β42 (Aβ42)-induced cytotoxicity in SH-SY5Y cells. The DPPH radical-scavenging activity and inhibitory effects on AChE were evaluated in vitro. The AChE inhibitory potential of 167 ligands, including cannabinoids, flavonoids, terpenoids, and alkaloids derived from Suk-Saiyasna, was assessed using ADMET analysis and molecular docking techniques. The results demonstrated that the Suk-Saiyasna extract exhibited a DPPH radical scavenging effect with an IC50 value of 27.40 ± 1.15 µg/mL and notable AChE inhibitory activity with an IC50 of 1.25 ± 0.35 mg/mL. Importantly, at a concentration of 1 µg/mL, the extract significantly protected cells from Aβ42-induced stress compared to controls. Docking studies revealed that delta-9-tetrahydrocannabinol (Δ9-THC), mesuaferrone B, piperine, β-sitosterol, and chlorogenic acid exhibited substantial binding affinities to AChE, surpassing reference drugs like galantamine and rivastigmine. Furthermore, in silico ADMET predictions indicated that Δ9-THC and piperine possessed favorable pharmacokinetic profiles, including solubility, absorption, and blood–brain barrier permeability, with no neurotoxicity or carcinogenicity associated with Δ9-THC.