“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.”
https://pubmed.ncbi.nlm.nih.gov/40243991/
“This study highlighted the potential of the Suk-Saiyasna herbal remedy in developing novel neuroprotective compounds for Alzheimer’s disease. The extracts of Suk-Saiyasna demonstrated significant antioxidant and acetylcholinesterase inhibitory activities, indicating their therapeutic applications. Molecular docking studies identified various active constituents with promising binding affinities, reinforcing their potential as acetylcholinesterase inhibitors.
Additionally, ADME predictions indicated favorable properties for Δ9-THC and piperine, underscoring their ability to cross the blood–brain barrier, which is crucial for neuroprotective effects. The safety evaluation of the extracts revealed moderate toxicity for piperine and Δ9-THC, while mesuaferrone B and chlorogenic acid displayed a safer profile. The inactivity of these compounds regarding hepatotoxicity and neurotoxicity further supported their potential use in therapeutic settings. However, concerns regarding carcinogenicity associated with piperine, donepezil, and galantamine necessitate rigorous safety assessments.
Overall, the findings from this research provide a foundation for the future exploration of Suk-Saiyasna as a promising source of natural antioxidants and neuroprotective agents.”