Investigation of Cannabis sativa Phytochemicals as Anti-Alzheimer’s Agents: An In Silico Study

Abstract

Cannabis sativa is a medicinal plant that has been known for years and is used as an Ayurvedic medicine. This plant has great potential in treating various types of brain diseases. Phytochemicals present in this plant act as antioxidants by maintaining synaptic plasticity and preventing neuronal loss. Cannabidiol (CBD) and Tetrahydrocannabinol (THC) are both beneficial in treating Alzheimer’s disease by increasing the solubility of Aβ42 amyloid and Tau aggregation. Apart from these therapeutic effects, there are certain unknown functions of these phytochemicals in Alzheimer’s disease that we want to elucidate through this study. In this research, our approach is to analyze the effect of phytochemicals in Cannabis sativa on multiple culprit enzymes in Alzheimer’s disease, such as AChE (Acetylcholinesterase), BChE (Butyrylcholinesterase), γ-secretase, and BACE-1. In this study, the compounds were selected by Lipinski’s rule, ADMET, and ProTox based on toxicity. Molecular docking between the selected compounds (THCV, Cannabinol C2, and Cannabidiorcol) and enzymes mentioned above was obtained by various software programs including AutoDock Vina 4.2, AutoDock, and iGEMDOCK. In comparison to Donepezil (BA = −8.4 kcal/mol, Ki = 1.46 mM), Rivastigmine (BA = −7.0 kcal/mol, Ki = 0.02 mM), and Galantamine (BA = −7.1, Ki = 2.1 mM), Cannabidiorcol (BA = −9.4 kcal/mol, Ki = 4.61 mM) shows significant inhibition of AChE. On the other hand, Cannabinol C2 (BA = −9.2 kcal/mol, Ki = 4.32 mM) significantly inhibits Butyrylcholinesterase (BuChE) in comparison to Memantine (BA = −6.8 kcal/mol, Ki = 0.54 mM). This study sheds new light and opens new avenues for elucidating the role of bioactive compounds present in Cannabis sativa in treating Alzheimer’s disease.

Network pharmacology-based approach to elucidate the pharmacologic mechanisms of natural compounds from Dictyostelium discoideum for Alzheimer's disease treatment

“…Swiss Target Prediction ( http://www.swisstargetprediction.ch/ ) [ 27 ] made the prediction of compound-based targets. Similarity between the compound-based targets and database-based targets were used for further network pharmacological analysis and validation through AutoDock [ 20 ].…”

“…Flavonoids, categorized as plant secondary compounds, possess antioxidant, anti -amyloidogenic, and anti-inflammatory properties and regulate cell-signaling pathways. Their demonstrated acetylcholinesterase inhibitory activity makes them a hopeful candidate for AD treatment [ 20 ]. In addition, terpenoids have many biological activities, and researchers have focused their attention on its anti-cholinesterase activity.…”

Exploring Cannabis sativa L for Anti-Alzheimer Potential: An extensive Computational Study including Molecular Docking, Molecular Dynamics, and ADMET Assessments

“…Many investigations have examined the potential bene ts of cannabis in addressing neurodegenerative diseases that affect cognitive abilities [20][21][22][23][24][25][26]. Additionally, the neuroprotective effect of this plant is widely studied and proven [27].…”

Computational Study on the Enzyme–Ligand Relationship between Cannabis Phytochemicals and Human Acetylcholinesterase: Implications in Alzheimer’s Disease

“…Fadaka et al 22 used molecular docking to predict potential compounds from C. sativa for Alzheimer's therapy. On the other hand, Patil et al 23 used three different molecular docking programs and concluded, as a first approximation, that THC, cannabinol (CBN), and cannabidiorcol would have some inhibitory effect on the enzymes AChE and BuChE (butyrylcholinesterase), which act as molecular targets of AD.…”