Screening the Synergistic Components of Acetylcholinesterase Inhibition from Phellodendron Bark Based on Fingerprint-Activity Relationship Modeling

Author:

Zhou Hong-Shan1,Luo Qi-Ming1,Lin Xiao-Bing1,Zhu Chuan-Sheng1,Li Ping1,Gao Wen1

Affiliation:

1. State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China

Abstract

Objective: Phellodendron chinense (PC) bark and Phellodendron amurense (PA) bark are two herbal medicines recorded in the Chinese Pharmacopoeia (2020 edition) that are easily mistaken for one another. In this study, the chemical constituents of PC and PA were compared using chromatographic fingerprints, and the potential synergistic acetylcholinesterase (AChE) inhibitor components were screened based on the correlation of fingerprint activity. Materials and Methods: Chromatographic fingerprints based on high-performance liquid chromatography were developed for the analysis and comparison of chemical compounds in PC and PA samples. The AChE inhibitory activity of PC and PA was determined using the Ellman method. Subsequently, the contribution of the characterized alkaloids in PC and PA to the overall AChE inhibition was modeled using partial least squares regression (PLSR). Results: The total alkaloid content in PC was higher than that in PA, which causes PC to have stronger anti-AChE activity. Overall, 13 and 20 common peaks were identified in the PC and PA samples, respectively. Among them, berberine (BER) was the dominant alkaloid in PC, which covered more than 65% of the total peak area in PC, but only approximately 25% of that in PA, indicating that the chemical composition is different between PC and PA. The spectrum–effect analysis based on PLSR and the correlation analysis showed that the BER-palmatine (PAL) and BER-jatrorrhizine (JAT) pairs have a synergistic inhibitory effect on AChE activity. Conclusions: A high-performance chromatographic fingerprint was established to distinguish PC and PA. The efficacy-associated markers were screened, including the pairs of BER-PAL and BER-JAT with anti-AChE activity, and the findings may assist with the quality control of PA and PC.

Publisher

Medknow

Subject

Complementary and alternative medicine

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