Molybdenum Nanoparticles Alleviate MC903-Induced Atopic Dermatitis-Like Symptoms in Mice by Modulating the ROS-Mediated NF-κB and Nrf2 /HO-1 Signaling Pathways.

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin condition that can affect individuals of all ages. Recent research has shown that oxidative stress plays a crucial role in the development of AD. Therefore, inhibiting oxidative stress may be an effective therapeutic approach for AD. Nano-molybdenum is a promising material for use as an antioxidant. We aimed to evaluate the therapeutic effects and preliminary mechanisms of molybdenum nanoparticles (Mo NPs) by using a murine model of chemically induced AD-like disease. Methods: HaCaT cells, a spontaneously immortalized human keratinocyte cell line, were stimulated by tumor necrosis factor-alpha /interferon-gamma after pre-treatment with Mo NPs. Reactive oxygen species levels, production of inflammatory factors, and activation of the nuclear factor kappa-B and the nuclear factor erythroid 2-related factor pathways were then evaluated. Mo NPs was topically applied to treat a murine model of AD-like disease induced by MC903, a vitamin D3 analog. Dermatitis scores, pruritus scores, transepidermal water loss and body weight were evaluated. AD-related inflammatory factors and chemokines were evaluated. Activation of the nuclear factor kappa-B and nuclear factor erythroid 2-related factor / heme oxygenase-1 pathways was assessed. Results: Our data showed that the topical application of Mo NPs dispersion could significantly alleviate AD skin lesions and itching and promote skin barrier repair. Further mechanistic experiments revealed that Mo NPs could inhibit the excessive activation of the nuclear factor kappa-B pathway, promote the expression of nuclear factor erythroid 2-related factor and heme oxygenase-1 proteins, and suppress oxidative stress reactions. Additionally, they inhibited the expression of thymic stromal lymphopoietin, inflammatory factors, and chemokines, thereby alleviating skin inflammation. Conclusion: Mo NPs present a promising alternative treatment option for patients with AD as they could address three pivotal mechanisms in the pathogenesis of AD concurrently.