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

[ Vol. 17 , Issue. 3 ]


Serseg Talia*, Khedidja Benarous, Meriem Lamrani and Mohamed Yousfi   Pages 360 - 377 ( 18 )


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 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 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.


Alzheimer's target enzymes, acetylcholinesterase, butyrylcholinesterase, β secretase, monoacylglycerol lipase, Lepidium sativum, Lepidine B & E, molecular docking.


Fundamental Science Laboratory, Amar Telidji University, Laghouat, Fundamental science laboratory, Amar Telidji University, Laghouat, Fundamental science laboratory, Amar Telidji University, Laghouat, Fundamental science laboratory, Amar Telidji University, Laghouat

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