Luteolin Modulates Oxidative Stress and Inflammatory Responses in Models of Atopic Dermatitis

Abstract Atopic dermatitis (AD) features persistent or recurrent skin inflammation, with oxidative stress also implicated in its development. Luteolin (Lut), a flavonoid sourced from plants, has been reported to attenuate inflammatory and oxidative responses; its effects in experimental AD require further characterization. To assess Lut in vivo and in vitro, we used 2,4-dinitrochlorobenzene (DNCB) to induce AD-like skin lesions in mice and exposed HaCaT keratinocytes to tumor necrosis factor-α (TNF-α) plus interferon-γ (IFN-γ). Luteolin treatment improved AD-like skin manifestations, reduced serum IgE levels, and alleviated histopathological alterations in DNCB-treated mice. Furthermore, elevated doses of Lut markedly diminished malondialdehyde (MDA) levels, whereas Lut lowered reactive oxygen species (ROS) concentrations, reinstated superoxide dismutase (SOD) activity, and mitigated inflammatory reactions in dermal tissues. In vitro, Lut inhibited intracellular ROS generation and decreased the production of cytokines that promote inflammation in activated HaCaT cells. Further experiments involving Nrf2 immunofluorescence and siRNA-induced knockdown of Nrf2 showed greater nuclear accumulation of Nrf2 after Lut treatment and supported a functional role for Nrf2 in Lut-induced changes in HO-1 and NQO1 expression and NF-κB phosphorylation. Together, these results add mechanistic support for the effects of Lut on redox balance and inflammation in these AD models.