Novel insights on acetylcholinesterase inhibition by Convolvulus pluricaulis,scopolamine and their combination in zebrafish  

作　　者：Kalyani Bindu Karunakaran Anand Thiyagaraj Kirankumar Santhakumar 

机构地区：[1]Supercomputer Education and Research Centre,Indian Institute of Sci-ence,Bengaluru,India [2]Department of Genetic Engineering,SRM Institute of Science and Technology,Kattankulathur 603203,India [3]Zebrafish Genetics Laboratory,Department of Genetic Engineering,SRM Institute of Science and Technology,Kattankulathur 603203,India

出　　处：《Natural Products and Bioprospecting》2022年第1期56-70,共15页应用天然产物（英文）

基　　金：financial assistance received from the Department of Biotechnology,Ministry of Science and Technology,New Delhi (BT/PR26189/GET/119/226/2017);DST-SERB,New Delhi (EMR/2017/000465).

摘　　要：Acetylcholinesterase(AChE)inhibitors increase the retention of acetylcholine(ACh)in synapses.Although they allevi-ate cognitive deficits in Alzheimer’s disease,their limited benefits warrant investigations of plant extracts with similar properties.We studied the anti-AChE activity of Convolvulus pluricaulis(CP)in a zebrafish model of cognitive impair-ment induced by scopolamine(SCOP).CP is a perennial herb with anti-amnesiac and anxiolytic properties.It contains alkaloid,anthocyanin,coumarin,flavonoid,phytosterol and triterpenoid components.Isoxazole(ISOX)was used as a positive control for AChE inhibition.CP-treated 168 hpf larvae showed a similar pattern of AChE inhibition(in the myelencephalon and somites)as that of ISOX-treated larvae.CP was superior to ISOX as evidenced by the retention of avoidance response behavior in adult zebrafish.Molecular docking studies indicated that ISOX binds Ser203 of the catalytic triad on the human AChE.The active components of CP-scopoletin and kaempferol-were bound by His447 of the catalytic triad,the anionic subsite of the catalytic center,and the peripheral anionic site.This suggested the ability of CP to mediate both competitive and non-competitive modes of inhibition.Surprisingly,SCOP showed AChE inhibition in larvae,possibly mediated via the choline-binding sites.CP+SCOP induced a concentration-dependent increase in AChE inhibition and ACh depletion.Abnormal motor responses were observed with ISOX,CP,ISOX+SCOP,and CP+SCOP,indicative of undesirable effects on the peripheral cholinergic system.Our study proposes the examination of CP,SCOP,and CP+SCOP as potential AChE inhibitors for their ability to modulate cognitive deficits.

关 键 词：Alzheimer’s disease ACETYLCHOLINESTERASE ZEBRAFISH Convolvulus pluricaulis SCOPOLAMINE ISOXAZOLE 

分 类 号：O62[理学—有机化学]