Afzelin resists UVA damage through autophagy and synergizes with ganoderic acid A to skin photoaging

Chronic UVA exposure accelerates photoaging by inducing oxidative stress and mitochondrial dysfunction. Autophagy maintains dermal homeostasis, but its decline promotes aging. Afzelin, a flavonoid with antioxidant activity, has not been fully studied for its autophagy-related photoprotective effects.

To determine whether afzelin protects against UVA-induced photoaging through autophagy and mitophagy activation, and to assess its synergy with ganoderic acid A (GAA), a triterpenoid possessing established anti-aging activity.

UVA-irradiated and D-galactose-induced senescence models of human dermal fibroblasts were examined by Western blotting, immunofluorescence, and flow cytometry. A 20-day UVA mouse model evaluated topical efficacy. Synergy was calculated using the Bliss model.

Afzelin restored UVA-impaired cell viability and reduced β-galactosidase, p53, and p21 while recovering Lamin B1. It lowered ROS levels and restored mitochondrial membrane potential (2.8-fold) via AMPK-AKT/mTOR-ULK1 and PINK1-Parkin activation. Combined with GAA (50 mM), afzelin showed strong synergy (Bliss = 67.6 ± 5.1). In vivo, co-treatment reduced epidermal thickness (∼37.3 %), restored collagen I and elastin, and suppressed p53/p21 expression.

Afzelin alleviates UVA-induced photodamage by activating autophagy and mitophagy. Together with the anti-aging triterpenoid GAA, it exerts synergistic anti-photoaging effects, supporting its potential as a natural autophagy-targeting agent for skin rejuvenation.