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 & E to inhibit AChE, BuChE, BACE, and MAGL. Hence, determining the main interactions in the inhibitor-enzyme complex. Methods: Inhibitory effect of Lepidium sativum, Juniperus phoenicea and Juniperus oxycedrus extracts on acetylcholinesterase using the Ellman method was investigated with Donepezil as the positive control. A molecular docking study is achieved using Autodock Vina. The structures of target molecules Lepidine B & E and the four enzymes were obtained from the 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 a positive control. The major components of alkaloids of L. sativum, Lepidine B & E bind 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 A beta aggregation. All the complexes of Lepidine B &E with the four enzymes show significant, several and different interactions. Conclusion: Our current study indicates that Lepidine B & E are promising anti-AD drugs and might become drug candidates to prevent Alzheimer's disease due to their multiple roles as potent inhibitors for AChE, BuChE, BACE, and MAGL. Indeed, they could inhibit A beta fibrillogenesis. No previous results about the inhibitory effect of Lepidine B & E on the AChE, BuChE, beta secretase, and monoacylglycerol lipase were reported.