# Photoprotective Effects of Quercetin and Hesperidin in Polymorphous Light Eruption: A Comparative Study with Alpha-Glucosylrutin

## TL;DR

This study compares natural flavonoids quercetin and hesperidin to a synthetic compound for protecting skin from UV damage, finding the natural mix more effective and safer.

## Contribution

The study introduces a safer, natural flavonoid complex as an effective alternative to synthetic photoprotective agents.

## Key findings

- An 8:1 quercetin:hesperidin complex outperformed alpha-glucosylrutin in restoring antioxidant enzymes and reducing inflammation.
- The complex reduced allergic response markers more effectively than the synthetic compound.
- Hesperidin maintained high cell viability across all tested concentrations, unlike quercetin at higher doses.

## Abstract

Polymorphous Light Eruption (PLE) is a prevalent UV-induced photodermatosis characterized by abnormal immune responses, oxidative stress, and cutaneous inflammation. Alpha-glucosylrutin (AGR), a chemically modified flavonoid widely used for its antioxidant and photoprotective effects, has shown clinical efficacy; however, its synthetic origin and classification as a potential skin sensitizer and aquatic toxin raise safety and environmental concerns. These limitations underscore the need for safer, naturally derived alternatives. In this study, we investigated the comparative efficacy of quercetin (QC) and hesperidin (HPN)—two plant-based flavonoids—against AGR in in vitro and ex vivo models of sun-induced skin damage. An optimized QC:HPN 8:1 (w/w) complex significantly restored antioxidant enzyme activities (SOD: 4.11 ± 0.32 mU/mg; CAT: 1.88 ± 0.04 mU/mg) and suppressed inflammatory cytokine production (IL-6: 155.95 ± 3.17 pg/mL; TNF-α: 62.34 ± 0.72 pg/mL) more effectively than AGR. β-hexosaminidase secretion, a marker of allergic response, was reduced to 99.02 ± 1.45% with QC:HPN 8:1, compared to 121.33 ± 1.15% with AGR. QC alone exhibited dose-dependent cytotoxicity at ≥10 μg/mL, whereas HPN maintained >94% cell viability at all tested concentrations. These findings highlight the QC:HPN 8:1 complex as a safe, natural, and effective alternative to synthetic AGR for preventing and managing PLE and UV-induced dermal inflammation. Further research should focus on clinical validation and formulation development for topical use.