Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by erythema, dryness, swelling, and persistent itching (Gatmaitan and Lee, 2023; Kim et al., 2023). The incidence of AD varies significantly across different ages, genders, and geographical regions, significantly impacting patients’ quality of life (Facheris et al., 2023; Tian et al., 2023). The exact pathogenesis of AD is very complicated, involving multiple factors, including genetic predisposition, immune dysregulation, skin barrier dysfunction, and environmental influences (Sroka-Tomaszewska and Trzeciak, 2021; Sugita, 2024).

Currently, topical corticosteroids are commonly used for patients with mild AD. However, long-term use may lead to side effects such as skin atrophy and hyperpigmentation (Alenazi, 2023; Eichenfield et al., 2014). For patients with severe symptoms, systemic treatments may be required, including biologics such as dupilumab and abrocitinib (Eichenfield et al., 2022; Reich et al., 2022). Despite the significant efficacy of these novel biologics, their application is limited due to side effects such as ocular discomfort, cardiovascular issues, and high treatment costs (Alves et al., 2022; Kamata and Tada, 2021; Kuznik et al., 2017). Therefore, the development of safe and effective alternative therapies has become an important focus of current research.

Chlorogenic acid (CGA), also known as caffeoylquinic acid, is a polyphenol widely found in various traditional Chinese medicinal plants and is renowned as the “gold of plants” (Wang et al., 2022a). CGA has various pharmacological effects, including anti-inflammatory (Wan et al., 2021), antioxidant (Li et al., 2023a), and immunomodulatory activities (Shi et al., 2020). It has significant therapeutic effects on diseases such as systemic lupus erythematosus (Wang et al., 2022b), colitis (Xu et al., 2024) and rheumatoid arthritis (Vyawahare et al., 2024). It is worth noting that CGA can be used as one of the quality control standards for traditional Chinese medicine (Zhang et al., 2018). It is a major component of several traditional Chinese medicine formulations, such as the Qingre-Qushi formula (Chen et al., 2017), the Pentaherbs formula (Tsang et al., 2016) and the Gu-ben-hua-shi formula (Jia et al., 2022; Li et al., 2023b). These formulations have been reported to alleviate symptoms of AD. Therefore, CGA holds potential application value in the treatment of AD. Further exploration of the efficacy and underlying mechanisms of CGA in treating AD is crucial for developing safe and effective alternative therapies.

In this study, we systematically investigated the therapeutic effects of CGA on AD by evaluating pathological parameters and cytokine levels in a DNCB-induced AD mouse model and TNF-α-stimulated HaCaT cells. Additionally, we explored the potential protective mechanisms of CGA using immunoblotting.