## 1 Introduction  
Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease that affects individuals of all ages, from childhood (15-20%) to adulthood (1-3%) worldwide [1]. The clinical symptoms are characterized by skin dryness, pruritus, erythema, scaling, and eczematous inflammation. The pathogenesis involves imbalanced immune responses to various allergens and defective skin barriers, which elevate immunoglobulin (Ig) E levels and activate T cells, particularly type 2-helper T cells (Th2), dendritic cells, mast cells, and eosinophils [2]. Consequently, allergic reactions stimulate the production of Th2-derived cytokines and chemokines, leading to an increase in the release of Th1-derived pro-inflammatory cytokines, including tumor necrosis factor (TNF)-\(\alpha\), interferon (IFN)-\(\gamma\) and various interleukin (IL) families, with elevated immune cell infiltrations in skin lesions [3, 4]. The incidence of AD is continuously increasing, posing a public health problem with a decline in the quality of life of patients and an increasing healthcare burden [5]. The treatment options include topical corticosteroids (i.e., dexamethasone), calcineurin inhibitors, antihistamines, antibiotics, and phototherapy [6]. However, they are limited to symptom management, and some of them can often be ineffective or have adverse effects in long-term use, such as immune suppression, hyperglycemia, and skin atrophy [7]. Thus, there is an unmet need to develop safe and effective treatments for AD.  
Red ginseng (the steamed root of _Panax ginseng_ [PERSON]) is a traditional medicine primarily used to treat various diseases, including inflammatory skin diseases in Korea, China, and Japan [8]. There have been many reports regarding the anti-allergic effects of red ginseng [9]. Furthermore, topical treatment with red ginseng has shown anti-AD effects in animal models by alleviating skin lesions and reducing IgE levels and the production of the relevant inflammatory mediators [10; 11; 12; 13; 14]. Clinical studies also support the anti-AD effects by showing improved clinical symptoms following a reduction in serum IgE levels [15; 16]. In particular, ginseng, including Rb1, Rb2, Rg3, Rh1, and Rh2, among compounds belonging to red ginseng, are believed to be responsible for the anti-AD effects via immune-modulating and anti-inflammatory pathways [2; 17; 18].  
Red ginseng marc (RGM) is a byproduct of red ginseng extraction, and it is usually treated as an industrial waste. However, increasing demand for red ginseng among patients finding more effective medications has aroused interest in the recycling of RGM. In this context, recent studies have shown evidence supporting the immunomodulatory, anti-inflammatory, antioxidant, and anticancer effects of RGM, despite small contents of bioactive components, such as ginseng, polyphenols, and flavonoids [19; 20; 21; 22]. Furthermore, the fermentation process of red ginseng and RGM has been reported to enhance the bioactive properties in AD [9]. Fermented RGM contains a greater proportion of ginsconsides, Rg2, Rg3, and Rh2 than non-fermented RGM, which enhances its antioxidant activities and incidental favorable effects [23; 24]. Our previous study showed that topical treatment of RGM extracts fermented with a complex of microorganisms promotes hair growth [25]. The fermented RGM contained crude ginensosides (1.7 mg/g) and polyphenols (9.8 mg/g), and the antioxidant activities were greater than those of the non-fermented form. It contained the anti-AD- or antioxidant-related ginscosides of Rb1 (0.6 mg/kg), Rb2 (0.9 mg/kg), Rg2 (12.1 mg/kg), Rg3 (9.6 mg/kg), and Rh1 (17.9 mg/kg). The other ginsconsides of Rb3 (1.8 mg/kg), Rc (1.9 mg/kg), Rd (3.5 mg/kg), Re (3.1 mg/kg), and Rf (3.9 mg/kg) were also detected. Thus, the anti-allergic effects of fermented RGM were examined in a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mice model.