ArticleFrontiers in pharmacology2021
Arecoline Enhances Phosphodiesterase 4A Activity to Promote Transforming Growth Factor-β-Induced Buccal Mucosal Fibroblast Activation via cAMP-Epac1 Signaling Pathway.
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- A Multifunctional Nucleic Acid Nanomedicine Coregulates Angiogenesis and Fibrosis to Treat Oral Submucous Fibrosis.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- The multistep progression of areca nut-induced oral cancer: a mechanistic roadmap from pathogenesis to precision therapy.Life medicine · 2026Review
- An organoid-guided roadmap for precision delivery of epigallocatechin gallate in oral submucous fibrosis.Frontiers in bioengineering and biotechnology · 2026Review
- Mechanistic Insights into Astragalus Membranaceus for Oral Submucosal Fibrosis: A Network Pharmacology and Experimental Approach.Current pharmaceutical design · 2026Article
- Impact of red-lime and white-lime betel quid on oral cell lines: Cytotoxicity and effects on fibronectin and type I collagen expression.Journal of dental sciences · 2025Article
- A Narrative Review of Prognostic Gene Signatures in Oral Squamous Cell Carcinoma Using LASSO Cox Regression.Biomedicines · 2025Review
- Source-specific metabolic profiles and gene expression in areca nut cultivars from Hainan (China).Frontiers in plant science · 2025Article
- Comprehensive insights into areca nut: active components and omics technologies for bioactivity evaluation and quality control.Frontiers in pharmacology · 2024Review
- The Controversial Roles of Areca Nut: Medicine or Toxin?International journal of molecular sciences · 2023Review
- Article
- Self-Confidence, Not Self-Awareness, Is Negatively Associated With Areca Nut Dependence.Frontiers in nutrition · 2022Article
- Arecoline Is Associated With Inhibition of Cuproptosis and Proliferation of Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma: A Potential Mechanism for Tumor Metastasis.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chewing areca nut (betel quid) is strongly associated with oral submucous fibrosis (OSF), a pre-cancerous lesion. Among the areca alkaloids, arecoline is the main agent responsible for fibroblast proliferation; however, the specific molecular mechanism of arecoline affecting the OSF remains unclear. The present study revealed that arecoline treatment significantly enhanced Transforming growth factor-β (TGF-β)-induced buccal mucosal fibroblast (BMF) activation and fibrotic changes. Arecoline interacts with phosphodiesterase 4A (PDE4A) to exert its effects through modulating PDE4A activity but not PDE4A expression. PDE4A silence reversed the effects of arecoline on TGF-β-induced BMFs activation and fibrotic changes. Moreover, the exchange protein directly activated by cAMP 1 (Epac1)-selective Cyclic adenosine 3',5'-monophosphate (cAMP) analog (8-Me-cAMP) but not the protein kinase A (PKA)-selective cAMP analog (N6-cAMP) remarkably suppressed α-smooth muscle actin(α-SMA) and Collagen Type I Alpha 1 Chain (Col1A1) protein levels in response to TGF-β1 and arecoline co-treatment, indicating that cAMP-Epac1 but not cAMP-PKA signaling is involved in arecoline functions on TGF-β1-induced BMFs activation. In conclusion, arecoline promotes TGF-β1-induced BMFs activation through enhancing PDE4A activity and the cAMP-Epac1 signaling pathway during OSF. This novel mechanism might provide more powerful strategies for OSF treatment, requiring further
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