Abstract
Atopic dermatitis (AD) is a common chronic skin disease driven by a T-cell-mediated immune response, with inflammation and pruritus being its main clinical manifestations. Huanglian Jiedu decoction (HLJDT), which is an ancient Chinese medicine herbal formula derived from Wai-Tai-Mi-Yao, is a potentially effective treatment for AD. We aimed to clarify the anti-inflammatory and anti-pruritus mechanisms of HLJDT in AD treatment. We performed immunohistochemistry, Western blotting, reverse transcriptase-polymerase chain reaction, Luminex-based direct multiplex immunoassay, enzyme-linked immunosorbent assays, and flow cytometry to address the abovementioned aims. HLJDT significantly reduced clinical symptoms and ear swelling in AD-like mice by inhibiting the production of cytokines [histamine, interleukin (IL)-3, IL-4, IL-5, IL-13, IL-17A, IL-31, and IL-33], substance P (SP), transient receptor potential cation channel subfamily V member 1 (TRPV-1), and gastrin-releasing peptide (GRP). Additionally, HLJDT significantly suppressed the protein expression levels and positive cell percentage of CD28, CD80, CD86, CD207, CD326, MHCII, and OX40 in the lymphoid nodes. Moreover, HLJDT significantly suppressed mRNA and protein expression of tyrosine–protein kinase (JAK1), histamine H4 receptor, and IL-4Rα, as well as the protein expression of GRP, SP, and TRPV-1 in the root ganglion. Our findings indicate that HLJDT can treat AD by regulating the antigen presentation function of dendritic cells, weakening T-lymphocyte activation, and subsequently exerting anti-inflammatory and anti-pruritus effects.
Highlights
Atopic dermatitis (AD) is a common, highly heritable chronic skin disease that is usually mediated by IgE and is clinically characterized by erythema, itch, eczema skin lesions, skin thickening, and inflammation (Badloe et al, 2020; Kuo et al, 2020)
Luminex-based direct multiplex immunoassay and Enzyme-linked immunosorbent assays (ELISA) revealed significantly increased serum histamine, IgE, IL-3, IL-4, IL-5, IL-13, IL-17A, IL-3,1 and IL-33 levels in the model group than in the control group (p < 0.01), which was indicative of abnormal cytokine secretion mainly related to inflammation and pruritus in the model group
12.8 g/kg Huanglian Jiedu decoction (HLJDT) inhibited the abnormal secretion of the aforementioned cytokines (p < 0.01) except for IgE (p > 0.05) (Figure 10A, see Discussion section); 6.4 g/kg HLJDT only significantly decreased IL-4 and IL-17A levels (p < 0.05), IL-3, IL-5, IL-13, and IL-33 (p < 0.01) compared with the levels in the model group
Summary
Atopic dermatitis (AD) is a common, highly heritable chronic skin disease that is usually mediated by IgE and is clinically characterized by erythema, itch, eczema skin lesions, skin thickening, and inflammation (Badloe et al, 2020; Kuo et al, 2020). The exact pathogenesis of AD remains unclear; it is widely considered to be induced by the complex interaction of skin barrier dysfunction and skin inflammation, with the involvement of environmental, genetic, and immunological factors; immunological abnormality is considered a key link The main effector cells of chronic skin lesions in AD are eosinophils and mast cells, which mediate numerous inflammatory molecules, including histamine, leukotriene, and interleukin, causing pruritus and mossy skin lesions in patients with AD. Anti-inflammatory and anti-pruritus effects are key factors in AD treatment
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