Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta

Jinliang Li; Fengchao Li; Guoxing Wu; Furong Gui; Hongmei Li; Lili Xu; Xiaojiang Hao; Yuhan Zhao; Xiao Ding; Xiaoping Qin

doi:10.3389/fpls.2023.1074184

Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta

Front Plant Sci. 2023 Feb 10:14:1074184. doi: 10.3389/fpls.2023.1074184. eCollection 2023.

Authors

Jinliang Li^{1

2}, Fengchao Li³, Guoxing Wu¹, Furong Gui¹, Hongmei Li¹, Lili Xu², Xiaojiang Hao², Yuhan Zhao², Xiao Ding², Xiaoping Qin¹

Affiliations

¹ State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, College of Plant Protection, Yunnan Agricultural University, Kunming, China.
² State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
³ College of Water Conservancy, Yunnan Agricultural University, Kunming, China.

Abstract

Plant-derived natural products are important resources for pesticide discovery. Acetylcholinesterase (AChE) is a well-validated pesticide target, and inhibiting AChE proves fatal for insects. Recent studies have shown that the potential of various sesquiterpenoids as AChE inhibitors. However, few studies have been conducted with eudesmane-type sesquiterpenes with AChE inhibitory effects. Therefore, in this research, we isolated two new sesquiterpenes, laggeranines A (1) and B (2), along with six known eudesmane-type sesquiterpenes (3-8) from Laggera pterodonta, and characterized their structures and the inhibitory effect they exerted on AChE. The results showed that these compounds had certain inhibitory effects on AChE in a dose-dependent manner, of which compound 5 had the best inhibitory effect with IC50 of 437.33 ± 8.33 mM. As revealed by the Lineweaver-Burk and Dixon plots, compound 5 was observed to suppress AChE activity reversibly and competitively. Furthermore, all compounds exhibited certain toxicity levels on C. elegans. Meanwhile, these compounds had good ADMET properties. These results are significant for the discovery of new AChE targeting compounds, and also enrich the bioactivity activity repertoire of L. pterodonta.

Keywords: Laggera pterodonta; acetylcholinesterase; enzyme kinetics; sesquiterpenes; toxic effects.

Grants and funding

This research was supported financially by grants from the Natural Science Foundation of Yunnan Province (202001AT070053, 202001AT070055, and 2019FY003003), grants of State Key Laboratory of Phytochemistry and Plant Resources in West China (P2019-ZZ06 and P2021-ZZ04), and the National Key R&D Program of China (2021YFD1400701). This study received funding from Science and Technology Planning Project of Yunnan Province of China National Tobacco Corporation (2021530000242030). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.