Sumontri_2025_Int.J.Mol.Sci_26_

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 beta42 (Abeta42)-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 IC(50) value of 27.40 +/- 1.15 microg/mL and notable AChE inhibitory activity with an IC(50) of 1.25 +/- 0.35 mg/mL. Importantly, at a concentration of 1 microg/mL, the extract significantly protected cells from Abeta42-induced stress compared to controls. Docking studies revealed that delta-9-tetrahydrocannabinol (delta(9)-THC), mesuaferrone B, piperine, beta-sitosterol, and chlorogenic acid exhibited substantial binding affinities to AChE, surpassing reference drugs like galantamine and rivastigmine. Furthermore, in silico ADMET predictions indicated that delta(9)-THC and piperine possessed favorable pharmacokinetic profiles, including solubility, absorption, and blood-brain barrier permeability, with no neurotoxicity or carcinogenicity associated with delta(9)-THC.