Inhibitory effects of serratene-type triterpenoids from Lycopodium complanatum on cholinesterases and β-secretase 1

- Two new and eight known serratene-type triterpenoids were isolated from Lycopodium complanatum.
- Isolated compounds exerted as inhibition of cholinesterase (ChEs) and BACE1.
- BACE1 inhibitors (1 and 6) have beneficial therapeutic potential for AD.

Phytochemical investigation of Lycopodium complanatum whole plants led to the isolation of two new serratene-type triterpenoids (1 and 2) along with eight known triterpenoids (3-10). Their structures were established using 1D and 2D NMR spectroscopic techniques and mass spectrometry. These compounds did not inhibit acetylcholinesterases (AChE) and butyrylcholinesterase (BChE), but did inhibit β-secretase 1 (BACE1). Compounds 1 and 6 showed potent BACE1 inhibition with IC50 values of 2.79 ± 0.28 and 2.49 ± 0.12 μM, respectively. The kinetic study of BACE1 inhibition revealed that compound 1 showed competitive inhibition, whereas 6 showed mixed-type inhibition. Furthermore, molecular docking results showed that the tested inhibitors 1 and 6 exhibited good binding affinities toward BACE1, with binding energies of −8.8 and −10.3 kcal/mol, respectively.

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