Elsevier

Fitoterapia

Volume 139, November 2019, 104378
Fitoterapia

Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity

https://doi.org/10.1016/j.fitote.2019.104378Get rights and content

Abstract

Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the aerial parts and roots of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC50 value of 0.525 ± 0.140 μM, which was comparable with the positive control, huperzine A (IC50 = 0.143 ± 0.029 μM).

Introduction

Alzheimer's disease (AD) is a progressive disease that destroys memory and other important mental functions [1]. The decreased levels of the neurotransmitter acetylcholine (ACh) in the cortex cause memory impairment in patients suffering from AD [2]. Thus, the acetylcholinesterase (AChE) inhibitors that block the cholinergic degradation of Ach are considered to be a promising approach for the treatment of AD [3,4]. Moreover, the AChE inhibitors prevent the assembly of β-amyloid peptide into amyloid plaque [5], which stimulates a great interest in searching for novel and potent AChE inhibitors for the treatment of AD.

The Lycopodium alkaloids are a unique class of compounds containing pyridine or α-pyridone ring, most of which were isolated from club moss belonging to the plant family Lycopodiaceae [6]. Huperzine A, a Lycopodium alkaloid from Huperzia serrata, acts as an AchE inhibitor that slows the cognitive decline associated with AD [7,8]. Lycopodiastrum casuarinoides (Spring) Holub ex R.D. Dixit is widely distributed in tropical and subtropical Asia. It is commonly known as “Shu Jin Cao” in Chinese and traditionally used for the treatment of contusions, strains, and swelling [9]. In previous studies, the ethanol extract of L. casuarinoides and several lycodine-type alkaloids from L. casuarinoides have been reported with potent anti-AchE activity [10,11]. Herein, further phytochemical investigation of the aerial parts and roots of L. casuarinoides collected from Jiangxi province of China was carried out to identify novel AChE inhibitors. The isolation and structure elucidation of five new (Fig. 1) and ten known lycodine-type alkaloids, as well as their anti-AChE properties were reported.

Section snippets

General experimental procedures

TLC was performed on pre-coated silica gel GF254 plates (Merck Chemical Co. Ltd., Shanghai, China). MCI (Polystyrene) gel (CHP20P, 75–150 μm, Mitsubishi Chemical Industries, Tokyo, Japan), silica gel (Qingdao Marine Chemical Industrials, Qingdao, Shandong, China), macro porous resin AB-8 (Shandong Lu Kang Chemical Industrials, Jinan, Shandong, China), and Sephadex LH-20 (Pharmacia Biotech AB, Uppsala, Sweden) were used for column chromatography (CC). Analytical HPLC was applied on a Waters 2695

Results and discussion

Compound 1, obtained as a white amorphous powder, showed an [M + H] + ion peak at m/z 305.1859 in its HRESIMS, corresponding to the molecular formula C17H24N2O3 (calcd. for C17H25N2O3, 305.1860). The IR absorption band at 3380 cm−1 (strong, broad) indicated the presence of hydroxy group in compound 1. The existence of α-pyridone moiety was revealed by the IR absorption band at 1653 cm−1 (α,β-unsaturated carbonyl group) and two characteristic proton signals [δH 7.84, 6.41 (each 1H, d, J

Conclusions

In summary, the aerial parts and roots of L. casuarinoides were thoroughly investigated, resulting in the identification of five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), along with ten known analogues. And huperzine C was found with moderate AchE inhibitory activity.

Declaration of competing interest

The authors declare no conflict of interest.

Acknowledgments

Financial support by the Research Fund of the Research Fund of University of Macau, Macao (MYRG2017-00109-ICMS and MYRG2018-00037-ICMS); National Natural Science Foundation of China, China (81573305, 81872754); the Strategic Priority Research Program of the Chinese Academy of Sciences, China (XDA12040106); the International Partnership Program of Chinese Academy of Sciences, China (153631KYSB20160004); the State Key Laboratory of Drug Research, China (SIMM1803KF-16).

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    These authors contributed equally to this work.

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