Related Experiment Video
Updated: Aug 27, 2026
Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
Quercetin Attenuates Vocal Fold Fibrosis via PI3K/AKT and MAPK Pathways: An Integrative Network Pharmacology and
Yujie Feng1, Qiurong Yang2, Yuanjia Hu1
1School of Medicine, Xiamen University, Xiamen, Fujian, China; Department of Otolaryngology - Head and Neck Surgery, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China; Xiamen Key Laboratory of Voice, Xiamen, Fujian, China.
Objective:
This study combined network pharmacology with in vivo and in vitro experiments to investigate the molecular mechanisms of quercetin against vocal fold fibrosis (VFI).
Methods:
Common targets of quercetin and VFI were identified via network pharmacology. A protein-protein interaction network was constructed, and key pathways were analyzed. Molecular docking was performed to evaluate binding affinity between quercetin and core targets. A rat model of vocal fold scar (in vivo) and TGF-β1-stimulated vocal fold fibroblasts (in vitro) were used to assess the expression of PI3K/AKT and MAPK pathway proteins, as well as changes in cell proliferation, migration, and apoptosis.
Results:
A total of 92 common targets were identified, with significant enrichment in the PI3K/AKT and MAPK pathways. Molecular docking showed binding energies < -5 kcal/mol for quercetin with PI3K, AKT1, and p38. In vivo, quercetin significantly inhibited the expression of PI3K, AKT, and p38 (P < 0.05). Moreover, quercetin and the PI3K inhibitor Alpelisib both significantly improved extracellular matrix organization, as evidenced by increased Energy, Correlation, and Homogeneity, and decreased Entropy and Contrast in gray-level co-occurrence matrix analysis (P < 0.05). Both treatments also restored hyaluronic acid and elastic fiber content in scarred vocal folds (P < 0.05). In vitro, quercetin suppressed the proliferation and migration of vocal fold fibroblasts (P < 0.05) and promoted apoptosis (P < 0.05).
Conclusion:
Quercetin exerts anti-fibrotic effects on vocal folds by multi-target inhibition of PI3K/AKT and MAPK signaling pathways, thereby modulating fibroblast behavior, preserving extracellular matrix integrity, and restoring key matrix components such as hyaluronic acid and elastic fibers.