Derma-Hc, a New Developed Herbal Formula, Ameliorates Cutaneous Lichenification in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic cutaneous disorder that is characterized by severe eczematous inflammation, swelling, and lichenification. Activation of T helper (Th)-22 cells by allergens leads to epidermal hyperplasia with hyperkeratosis at the chronic phase of AD. Derma-Hc is composed of five natural herbs with anti-AD effects, such as Astragalus membranaceus BUNGE, Schizonepeta tenuifolia Briq., Cryptotympana pustulata Fabr., Angelica sinensis Diels, Arctium lappa L. In this study, the ameliorative effect of Derma-Hc on cutaneous lichenification in 2,4-dinitrochlorobenzne (DNCB)-induced AD was investigated. The dorsal skin of mice was sensitized with DNCB to induce AD-like skin lesions. The dermatitis score and frequency of scratching were evaluated. Thickness of epidermis and dermis was measured by staining with H&E. In addition, infiltration of the mast cell was observed by staining with toluidine blue. Then, desmosomal cadherin, DSC1 was examined by immunofluorescence. Pathological mechanisms involved in lichenification were analyzed in AD-like skin lesions and TNF-α + IFN-γ-treated with human keratinocytes including keratinocyte differentiation genes and JAK1-STAT3 signaling pathway with IL-22 by RT-PCR and western blotting. Topical treatment of Derma-Hc improved AD-like symptoms such as dryness, edema and lichenefication and decreased the number of scratches. Histopathological analysis demonstrated that Derma-Hc significantly inhibited epidermal hyperplasia, hyperkeratosis, and mast cells infiltration. In addition, the level of DSC1 was highly expressed in the epidermis by Derma-Hc. Moreover, mRNA expression level of FLG, an epidermal differentiation complex gene, was recovered by Derma-Hc treatment. KLK5 and KLK7 were markedly reduced to normalize keratinocyte differentiation in dorsal skin tissues and human keratinocytes. On the other hand, Derma-Hc restored expression level of SPINK5. In addition, Derma-Hc inhibited IL-22 via the blockade of JAK1-STAT3 signal pathway. Taken together, Derma-Hc, a natural herbal formula, regulated keratinocyte differentiation and inhibited epidermal hyperplasia with hyperkeratosis. Therefore, Derma-Hc could be a promising candidate for treating chronic AD through modulating signaling of IL-22-associated skin lichenification.

Phosphorylation of Janus kinase 1 and signal transducer and activator of transcription 3 and 6 in keratinocytes of canine atopic dermatitis

“…31,32 In a mouse model of AD, the transcription level of IL-22 was increased in secondary lesions with lichenification in which pSTAT3 also was detected. 33 Secondary lesions with a large number of pSTAT3positive keratinocytes in the present study showed a thickened epidermis (Figure 2c); therefore, the phosphorylation of STAT3 may have been induced by IL-22 in cAD, similar to the findings in the mouse model. Further studies are needed to investigate the role of IL-22 in the phosphorylation of STAT3 in cAD and its effect on epidermal proliferation.…”

“…Interleukin‐22 is a cytokine that induces acanthosis in the chronic phase of AD 31,32 . In a mouse model of AD, the transcription level of IL‐22 was increased in secondary lesions with lichenification in which pSTAT3 also was detected 33 . Secondary lesions with a large number of pSTAT3‐positive keratinocytes in the present study showed a thickened epidermis (Figure 2c); therefore, the phosphorylation of STAT3 may have been induced by IL‐22 in cAD, similar to the findings in the mouse model.…”

Lithospermum erythrorhizon Alleviates Atopic Dermatitis-like Skin Lesions by Restoring Immune Balance and Skin Barrier Function in 2.4-Dinitrochlorobenzene-Induced NC/Nga Mice

“…IgE secretion is increased in B cells by the Th2-mediated cytokine IL-4 [ 57 ], and the degranulation of mast cells by IgE increases itching through the release of histamine [ 27 , 58 ]. Continuous scratching can increase erythema, abrasions, and erosions, along with lichenification, which thickens the skin [ 59 , 60 , 61 ]. In addition, damage to the skin barrier caused by this scratching can further cause loss of moisture, leading to dry skin [ 62 ].…”

The Slough of Cicadidae Periostracum Ameliorated Lichenification by Inhibiting Interleukin (IL)-22/Janus Kinase (JAK) 1/Signal Transducer and Activator of Transcription (STAT) 3 Pathway in Atopic Dermatitis

“…Accordingly, the skin gets thickened and leathery, which is known as 'lichenification', a severe symptom of AD (Nam et al, 2021).…”