Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by eczematous lesions, intense itch, and significant discomfort (Fishbein et al., 2020). Termed as the first step of the ‘atopic march’, AD manifests with relapsing-remitting patterns and is closely associated with a higher incidence of mental health issues and other atopic disorders, such as anxiety, sleep disturbance, food allergy, asthma, and allergic rhinitis. It is estimated to affect approximately 20% of children and 10% of adults globally (Mayba and Gooderham, 2017; Paller et al., 2018; Schneider et al., 2016). The significant burden that AD places on patients' daily lives, combined with its financial implications, underscores the pressing need for optimal disease control (Ali et al., 2020). And the complex etiology of AD makes the development of effective treatments a challenge, further emphasizing this need (Schuler et al., 2023).

The pathogenesis of AD is multifaceted, implicating genetic predispositions, environmental triggers, skin barrier disruptions, and immune dysregulation (Langan et al., 2020). Hallmarked by excessive Type 2 immune responses, various triggers such as allergens, microbes, and mechanical injury disrupt the skin barrier and activate the innate immune system (Furue et al., 2019). This cascade eventually leads to overexpression of Th2 cytokines like IL-4, IL-5, IL-13 and IL-31(Sroka-Tomaszewska and Trzeciak, 2021). The subsequent induction of the IgE isotype switching in B-lymphocytes and mast cells activation exacerbates inflammation (Tanaka and Furuta, 2021). In that way, the management of AD should primarily focus on controlling inflammation and immune dysregulation.

Over the past decades, AD therapy has centered on the use of systemic or local immunomodulators, including corticosteroids and calcineurin inhibitors. However, these treatment modalities often come with adverse effects, and tolerance or dependence could develop over time (Ashcroft et al., 2005; Newsom et al., 2020; Puar et al., 2021). Although recent advancements in medical technology have introduced novel treatment options, such as Dupilumab and oral JAK-inhibitors (Rodrigues et al., 2019; Worm et al., 2020), their safety profiles, high relapse rate due to the chronic nature of AD, and the potential financial burden for patients limit their use (Jia et al., 2022; Shalabi et al., 2022). Therefore, the need for exploring more efficient and cost-effective therapeutic approaches becomes evident. In this context, natural products and alternative medicine, due to their reported efficacy and lower risk of side effects, appear as promising strategies for the prevention and treatment of immune-inflammatory diseases (Goh et al., 2021).

Qing-Re-Chu-Shi Decoction (QRCSD), a traditional herbal formula, prepared using 9 medicinal plants, has a rich history of use in Chinese medicine for treating a variety of inflammatory skin conditions, including eczema, atopic dermatitis, neurodermatitis and psoriasis. Its application, pioneered by the renowned Chinese dermatologist Zhao Bingnan, was primarily aimed at 'clearing heat' (Qing-re) and 'removing dampness' (Chu-shi). The prescription is widely recognized and utilized in clinical settings for its efficacy in treating dermatological conditions attributed to the pathogenic influences of damp-heat according to Traditional Chinese Medicine principles. Dr. Zhu Huiting has succinctly summarized Zhao Bingnan's clinical expertise in treating AD, highlighting the efficacy of QRCSD in patients with damp-heat symptoms. This review, enriched by detailed case studies, underscores the decoction's ability to alleviate symptoms like skin redness, erythema, rash exudation, and itching, providing a concise yet comprehensive insight into its therapeutic value for AD (Zhu et al., 2019). Dr. Yang Lan's team also conducted a comprehensive literature review on QRCSD, elucidating its therapeutic efficacy in treating damp-heat-related dermatological disorders. Their analysis revealed a notable cure rate of 90.1% in 440 cases of acute eczema and dermatitis, and also demonstrated effectiveness in managing AD and herpes zoster (Yang et al., 2019). Aligning with the traditional Chinese Medicine principle of 'treating different diseases with the same therapeutic strategy,' these insights pave the way for extending the application of QRCSD to a wider spectrum of damp-heat related dermatological conditions, including acne, seborrheic dermatitis, psoriasis, and steroid-dependent dermatitis.The relevance of these traditional concepts to modern scientific understanding of inflammatory and immune processes suggests a potential role for QRCSD in managing conditions like atopic dermatitis. Existing clinical research suggests that Qing-Re-Chu-Shi therapies can modulate immune factors like IL-17, IL-23 (Zhang et al., 2021). However, comprehensive studies elucidating the biological activity of QRCSD are currently lacking.

We have recently found that QRCSD exhibits anti-inflammatory and immunomodulatory properties in AD treatment, suggesting the potential presence of anti-inflammatory and immune-regulating substances within this herbal remedy. The current study aims to explore the modulatory role and mechanistic action of QRCSD in AD. We used 1-choloro-2,4-dinitrobenzene (DNCB) to induce AD-like skin lesions in NC/Nga mice and evaluated whether QRCSD treatment could attenuate symptoms and regulate the production of pro-inflammatory and Th2-related cytokines in AD-like skin lesions.