南方医科大学学报2024，Vol.44Issue(5)：930-940,11.DOI:10.12122/j.issn.1673-4254.2024.05.15
槟榔活性成分诱导口腔黏膜下纤维化的机制:基于网络药理学结合临床样本验证
Oral submucosal fibrosis induced by active components in areca nut:a network pharmacology-based analysis and validation of the mechanism
摘要
Abstract
Objective To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis(OSF)and the possible mechanism.Methods The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software.The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia(2015),PubChem,Chemical book,and SciFinder databases.The potential active components,core targets,biological functions and signaling pathways affecting OSF were analyzed by network pharmacology.The targets of OSF were obtained by integrating Genecards and KEGG databases.The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine(TCMSP),and the target-compound,compound-TCM,target-compound-TCM network was constructed.Molecular docking was used to analyze the component-target binding.Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF.Results The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways.In the clinical samples,the expressions of PI3K protein decreased and the expressions p-PI3K,AKT1 and P-Akt all increased significantly in OSF tissue,where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected.The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals.Conclusion The main active ingredients including arecoline,arecaine,and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia,thus leading to the occurrence of oral submucosal fibrosis.关键词
槟榔/口腔黏膜下纤维化性变/网络药理学/分子对接Key words
areca nut/oral submucosal fibrosis/network pharmacology/molecular docking引用本文复制引用
李睿镈,高歌,谢曦,罗海彬..槟榔活性成分诱导口腔黏膜下纤维化的机制:基于网络药理学结合临床样本验证[J].南方医科大学学报,2024,44(5):930-940,11.基金项目
国家自然科学基金(82360731) （82360731）
海南省自然科学基金(821MS027,823RC467,KJRC2023B10) Supported by National Natural Science Foundation of China(82360731). （821MS027,823RC467,KJRC2023B10）
