Analysis of Inhibitory Effect of Berberine Compounds on Acetylcholinesterase and Blood-brain Barrier Permeability
10.13422/j.cnki.syfjx.20240411
- VernacularTitle:小檗碱类成分对乙酰胆碱酯酶的抑制作用及血脑屏障透过性分析
- Author:
Fulu PAN
1
;
Yang LIU
1
;
Huining LIU
1
;
Shuang YU
1
;
Xueyan LI
1
;
Xinyu WANG
1
;
Dongying QI
1
;
Xiaoyu CHAI
1
;
Qianqian WANG
1
;
Zirong YI
1
;
Yanli PAN
2
Author Information
1. School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 102488， China
2. Institute of Information on Traditional Chinese Medicine， China Academy of Chinese Medical Sciences， Beijing 100700， China
- Publication Type:Journal Article
- Keywords:
columbamine;
acetylcholinesterase;
drug-target binding;
affinity;
blood-brain barrier
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(9):116-124
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo examine the inhibitory effects of berberine compounds， including columbamine， on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier （BBB） permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration （IC50） of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters （Koff） of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds （including medicinal herbs and compound formulas） was conducted using ultra performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS）. ResultBerberine compounds， including columbamine， exhibited strong inhibition of acetylcholinesterase， with IC50 values in the nanomolar range. Moreover， they displayed better drug-target binding kinetics characteristics （with smaller Koff values） than the positive control of donepezil hydrochloride （P<0.01）， indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer， as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance， this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease， providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.
