Objective:
This study aimed to investigate the therapeutic effects and mechanisms of quercetin compared with traditional drugs in the treatment of vocal fold fibrosis.

Methods:
A rat model of vocal fold scarring was established, followed by cellular and in vitro experiments. The rats were randomly divided into five groups: normal control, vocal fold injury, quercetin, 5-fluorouracil, and dexamethasone groups. The antifibrotic effects of quercetin, 5-fluorouracil, and dexamethasone were compared.

Results:
Alcian blue and modified EVG staining showed that compared with the normal control group, quercetin at doses of 100 mg/kg/day and 200 mg/kg/day increased hyaluronic acid levels in the vocal fold lamina propria and inhibited the proliferation of elastic fibers (P < 0.05). The inhibitory effect was significantly better than or comparable to that of 5-fluorouracil and dexamethasone (P 0.05), while their expression levels were decreased in the quercetin group (P > 0.05). The reductions were significantly different from those in the 5-fluorouracil and dexamethasone groups (P < 0.05).

The CCK-8 assay showed that fibroblast proliferation was significantly inhibited at 48 hours in the quercetin group (P < 0.05), and the inhibitory effect increased with higher doses and longer treatment duration. Colony formation assays revealed that quercetin more effectively inhibited fibroblast proliferation compared with 5-fluorouracil and dexamethasone (P < 0.05).

Western blot analysis of FN1 (fibronectin) and COL1A1 (type I collagen) showed that both proteins were upregulated in the vocal fold injury group. In contrast, quercetin treatment suppressed the expression of FN1 and COL1A1. At concentrations of 25–200 μM, quercetin significantly inhibited FN1 and COL1A1 expression more effectively than or comparably to 5-fluorouracil and dexamethasone (P < 0.05).

Conclusion:
This study suggests that quercetin exhibits a strong antifibrotic effect in vocal fold injury and may serve as a promising alternative to traditional drugs such as 5-fluorouracil and dexamethasone in the treatment of vocal fold scarring.

Keywords: Quercetin, Dexamethasone, 5-fluorouracil, Vocal fold injury, Vocal fold scarring, Fibrosis, Therapeutic comparison