Potential bioactive compounds and mechanisms of Fibraurea recisa Pierre for the treatment of Alzheimer's disease analyzed by network pharmacology and molecular docking prediction

Shishuai Wang; Yixuan Ma; Yuping Huang; Yuhui Hu; Yushan Huang; Yi Wu

doi:10.3389/fnagi.2022.1052249

Potential bioactive compounds and mechanisms of Fibraurea recisa Pierre for the treatment of Alzheimer's disease analyzed by network pharmacology and molecular docking prediction

Front Aging Neurosci. 2022 Dec 8:14:1052249. doi: 10.3389/fnagi.2022.1052249. eCollection 2022.

Authors

Shishuai Wang^{1

2

3}, Yixuan Ma^{1

2

3}, Yuping Huang⁴, Yuhui Hu⁵, Yushan Huang², Yi Wu^{1

6}

Affiliations

¹ Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China.
² Center for Evidence Based Medical and Clinical Research, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
³ College of Pharmacy, Gannan Medical University, Ganzhou, China.
⁴ Department of Biochemistry and Molecular Biology, Gannan Medical University, Ganzhou, China.
⁵ Medical College, Jinggangshan University, Ji'an, China.
⁶ Jiangxi Province Key Laboratory of Biomaterials and Biofabrication for Tissue Engineering, Gannan Medical University, Ganzhou, China.

Abstract

Introduction: Heat-clearing and detoxifying Chinese medicines have been documented to have anti-Alzheimer's disease (AD) activities according to the accumulated clinical experience and pharmacological research results in recent decades. In this study, Fibraurea recisa Pierre (FRP), the classic type of Heat-clearing and detoxifying Chinese medicine, was selected as the object of research.

Methods: 12 components with anti-AD activities were identified in FRP by a variety of methods, including silica gel column chromatography, multiple databases, and literature searches. Then, network pharmacology and molecular docking were adopted to systematically study the potential anti-AD mechanism of these compounds. Consequently, it was found that these 12 compounds could act on 235 anti-AD targets, of which AKT and other targets were the core targets. Meanwhile, among these 235 targets, 71 targets were identified to be significantly correlated with the pathology of amyloid beta (Aβ) and Tau.

Results and discussion: In view of the analysis results of the network of active ingredients and targets, it was observed that palmatine, berberine, and other alkaloids in FRP were the key active ingredients for the treatment of AD. Further, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis revealed that the neuroactive ligand-receptor interaction pathway and PI3K-Akt signaling pathway were the most significant signaling pathways for FRP to play an anti-AD role. Findings in our study suggest that multiple primary active ingredients in FRP can play a multitarget anti-AD effect by regulating key physiological processes such as neurotransmitter transmission and anti-inflammation. Besides, key ingredients such as palmatine and berberine in FRP are expected to be excellent leading compounds of multitarget anti-AD drugs.

Keywords: AD pathology; Alzheimer’s disease; Fibraurea recisa Pierre; alkaloids; heat-clearing and detoxifying traditional Chinese medicine; network pharmacology.