Lepidine B from Lepidium Sativum Seeds as Multi-Functional Anti-Alzheimer’s Disease Agent: In Vitro and In Silico Studies

OBJECTIVE: The present study is carried out to screen the anticholinesterase effect of the total alkaloids of L. sativum seeds and other plants, and studied the ability of Lepidine B to inhibit AChE, BuChE, BACE and MAGL. and the main interactions in inhibitor-enzyme complex. METHOD: Inhibitory effect extracts from Lepidium sativum, Juniperus phoenicea and Juniperus oxycedrus on acetylcholinesterase using Ellman method have been investigated using Donepezil as positive control. Molecular docking study carried out using Autodock vina. The structures of studied molecules Lepidine B, Galantamine and Donepezil were obtained from PubChem database and Protein databank. RESULTS: Alkaloidal extract of Lepidium sativum and ethyl acetate extracts of Juniperus phoenicea and Juniperus oxycedrus exhibit a strong acetylcholinesterase inhibitory activity with IC50 values of 0.59 +/- 0.04, 0.57 +/- 0.00 and 0.49 +/- 0.00 mg/mL, respectively using Donepezil <0.25 mg/mL as positive control. The major component of alkaloid of L. sativum, Lepidine B bind so tightly to AChE and BuChE as much as galantamine and donepezil. We suggest that Lepidine B is a non-competitive inhibitory by interacting with PAS of AChE and BuChE, therefore it is capable to prevent the HuAChE-induced Abeta aggregation. We have found significant interactions in the Lepidine B-BACE and Lepidine B-MAGL complexes. CONCLUSION: The docking study indicate that Lepidine B is a promising anti-AD drug and might become a drug candidate to prevent Alzheimer's disease due to its multiple roles as potent inhibitor for AChE, BuChE, BACE and MAGL, also inhibitor for Abeta fibrillogenesis. No previous results about the inhibitory effect Lepidine B on the AChE, BuChE, beta secretase and monoacylglycerol lipase have been reported.