Atopic dermatitis (AD) is one of the most common chronic inflammatory diseases, affecting over 20% of children and 10% of adults worldwide (Odhiambo et al., 2009; Silverberg and Hanifin, 2013). Although the incidence of AD has stabilized in developed countries, the incidence of AD is gradually increasing worldwide (Langan et al., 2020). AD is characterized by intense pruritus and recurrent eczematous lesions, and the intensity of itching positively correlates with the severity of the disease. Emotional stress, humid conditions, sweating due to exercise or heat, and exposure to allergens are all factors that can worsen itching. However, scratching can cause skin damage, bleeding, and crusting, resulting in generalized lichenification and nodular itching. These diverse clinical symptoms cause severe discomfort, frequently affecting the patients’ daily lives and work, and ultimately lead to depression, anxiety, and even suicide (Ständer, 2021).

In AD, transantigen-presenting CD4+ T cells cause immediate release of alarm cytokines, such as IL-1β (interleukin-1β), IL-25, IL-33, and thymic stromal lymphoprotein (TSLP), from keratin-forming cells. In turn, this causes the release of high levels of Th2 marker cytokines (such as IL-4, IL-5, and IL-13), promoting immunoglobulin E (IgE) class switching and eosinophil recruitment (Chovatiya and Paller, 2021; Czarnowicki et al., 2019). Despite the prevalence of Th2 overexpression in patients with AD, the role of other helper T cells in AD should not be overlooked, especially Th17 cells, which have been reported in several studies to be more highly expressed in children and adult Asian patients (Chan et al., 2018; Noda et al., 2015; Wang et al., 2020). Moreover, oxidative stress caused by reactive oxygen species (ROS) has been proven to be an important factor leading to AD (Gao et al., 2022; Yan et al., 2022). A surge in oxidative stress can induce the release of IgE and cause degranulation of mast cells bound to IgE (Yamashita et al., 2009). In AD, ROS induce the activation of NLRP3 inflammasomes, which is the main factor leading to the over-differentiation of Th17 cells (Lin et al., 2021). Accordingly, differentiated Th17 cells release IL-17, further inducing the activation of NLRP3 inflammatory bodies (Lei et al., 2021).

The activation of NLRP3 inflammasomes plays a key role as inflammatory mediators in allergic diseases (Xiao et al., 2018). Hence, regulating NLRP3 inflammasomes may be an important treatment modality for AD. In many chronic diseases, autophagy could achieve therapeutic effects by negatively regulating the activation of NLRP3 inflammasomes (Biasizzo and Kopitar-Jerala, 2020; Cao et al., 2019). Previous studies suggested that autophagy is increased in AD; however, in a recent study, although there was an increase in the initiation and formation of autophagy in AD, the autophagy ability of lysosomes was impaired (Hailfinger and Schulze-Osthoff, 2021). SQSTM1/p62 is a multifunctional protein that comprises six functional regions. This structure is the center of multiple signaling pathways and participates in maintaining and regulating essential cellular functions (Ma et al., 2019). As an important selective autophagic adaptor protein, p62 participates as a receptor in scavenging ubiquitinated proteins (Beckers et al., 2021). It was found that p62 links ubiquitinated proteins and LC3/Atg8 through the phosphorylation of its UBA (Ser 405) and LIR (Ser 351/349) domains, delivering the ubiquitinated substrates to the autophagic lysosome to complete their degradation (Lamark et al., 2017). In addition, p62 transports ubiquitinated proteins to the proteasome for degradation (Peng et al., 2020). To date, no potential therapeutic drugs have been found to improve AD by regulating p62. Further research is needed to find effective therapeutic drugs for AD that work by regulating the p62 axis.

Lonicera japonica Thunb., also known as Jin Yin Hua or the Japanese honeysuckle, belongs to the family Caprifoliaceae and has been widely cultivated in Fengqiu County, Henan Province, China, for thousands of years. It has been used in various Asian countries as a food ingredient, herbal tea, traditional medicines, and health products (Bai et al., 2020a, Bai et al., 2020b). Lonicera japonica polysaccharides have diverse pharmacological activities including anti-inflammatory (Yang et al., 2019), antioxidative (Zhang et al., 2020a, Zhang et al., 2020b), and immunoregulatory activities (Zhou et al., 2018). Lonicera japonica Thunb. has been used in the Chinese herbal medicine (CHM) for thousands of years, and a study of CHM prescriptions for AD in Taiwan found that 11% of prescriptions included Lonicera japonica Thunb. (Chen et al., 2015). A randomized, double-blind, placebo-controlled study found that the Pentaherbs formula, which comprises five herbs including Lonicera japonica as the monarch drug, significantly improved the quality of life of children with moderate to severe AD and reduced the use of topical steroids (Hon et al., 2007). However, the mechanism of Lonicera japonica polysaccharides in the treatment of AD has not been clarified and further studies are required. Polysaccharides are among the main components of Lonicera japonica. Some studies have found that Lonicera japonica polysaccharide can alleviate allergy. Furthermore, some studies have found that Lonicera japonica crude polysaccharide can attenuate inflammatory signals by inhibiting NLRP3 inflammasomes (Liu et al., 2019). Therefore, this study investigated the potential pharmacological effects and mechanism of the homogeneous polysaccharide WLJP-025p (water-extracted Lonicera japonica polysaccharide) (Bai et al., 2022) previously isolated from Lonicera japonica on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin disease.