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 inhibitorenzyme
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 noncompetitive
inhibitory by interacting with PAS of AChE and BuChE, therefore it is capable to prevent
the HuAChE-induced Aβ 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 Aβ fibrillogenesis. No
previous results about the inhibitory effect of Lepidine B & E on the AChE, BuChE, β secretase,
and monoacylglycerol lipase were reported.