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[Oral submucosal fibrosis induced by active components in areca nut: a network pharmacology-based analysis and
1Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmacy, Hainan University, Haikou 570228, China.
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 PAkt 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.
Insights
Areca nut
Area of Science:
- Pharmacology
- Oral pathology
- Molecular biology
Context:
- Areca nut consumption is linked to oral submucosal fibrosis (OSF).
- The specific active components and mechanisms driving OSF remain incompletely understood.
- Identifying these factors is crucial for developing targeted interventions.
Purpose:
- To identify pharmacologically active components in areca nut that induce OSF.
- To elucidate the molecular mechanisms underlying OSF pathogenesis.
- To investigate the role of PI3K-Akt and MAPK signaling pathways in OSF.
Summary:
- Areca nut contains active ingredients like arecoline, arecaine, and guvacine.
- These compounds activate PI3K-Akt and MAPK pathways, increasing inflammatory mediators (IL-6, IL-8) and collagen.
- This leads to collagen hyperplasia and the development of oral submucosal fibrosis.
Impact:
- Provides insights into the molecular basis of OSF induced by areca nut.
- Highlights the involvement of PI3K-Akt and MAPK pathways in OSF.
- Identifies key inflammatory mediators and active components for potential therapeutic targets.
