Isoflavone-Rich Fraction of Traditional Thai Fermented Soybean (Thua Nao) Protects Dermal Fibroblasts from Photoaging by Modulating MAPK and Akt Signaling Pathways

Ultraviolet B (UVB) irradiation is a major environmental factor contributing to skin photoaging by inducing oxidative stress, apoptosis, inflammation, and extracellular matrix degradation in dermal fibroblasts. This study investigated the photoprotective effects of Thua Nao, a Thai fermented soybean, against UVB-induced human dermal fibroblast damage, and explores its underlying mechanisms. The dichloromethane fraction of Thua Nao (TN-DC) most effectively mitigated UVB-induced cell death. HPLC analysis identified daidzein and glycitein as the major constituent isoflavones in TN-DC that protect fibroblasts against UVB-induced cellular damage. Mechanistically, they reduced apoptosis by suppressing caspase-9/3 activation and preserving mitochondrial membrane potential. Additionally, they suppressed inflammatory mediators (IL-6, IL-8, iNOS, COX-2) and prevented collagen loss. These protective outcomes correlated with decreased intracellular reactive oxygen species and upregulated endogenous antioxidant enzymes (SOD-1, HO-1). Signaling pathway analysis revealed that TN-DC activated the pro-survival ERK1/2 and Akt pathways in UVB-exposed cells. Conversely, daidzein and glycitein selectively attenuated JNK MAPK activation, downregulating downstream pro-inflammatory cytokines and mediators. Collectively, these findings demonstrate that TN-DC protects human dermal fibroblasts against UVB-induced photoaging primarily by enhancing endogenous antioxidant defense, thereby preserving cellular homeostasis through coordinated regulation of oxidative stress-responsive signaling pathways.