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Mar Drugs
2021 Nov 01;1911:. doi: 10.3390/md19110622.
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Echinochrome A Treatment Alleviates Atopic Dermatitis-like Skin Lesions in NC/Nga Mice via IL-4 and IL-13 Suppression.
Yun HR
,
Ahn SW
,
Seol B
,
Vasileva EA
,
Mishchenko NP
,
Fedoreyev SA
,
Stonik VA
,
Han J
,
Ko KS
,
Rhee BD
,
Seol JE
,
Kim HK
.
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Atopic dermatitis (AD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to dryness, pruritus, and erythematous lesions. AD is triggered by immune imbalance and oxidative stress. Echinochrome A (Ech A), a natural pigment isolated from sea urchins, exerts antioxidant and beneficial effects in various inflammatory disease models. In the present study, we tested whether Ech A treatment alleviated AD-like skin lesions. We examined the anti-inflammatory effect of Ech A on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions in an NC/Nga mouse model. AD-like skin symptoms were induced by treatment with 1% DNCB for 1 week and 0.4% DNCB for 5 weeks in NC/Nga mice. The results showed that Ech A alleviated AD clinical symptoms, such as edema, erythema, and dryness. Treatment with Ech A induced the recovery of epidermis skin lesions as observed histologically. Tewameter® and Corneometer® measurements indicated that Ech A treatment reduced transepidermal water loss and improved stratum corneum hydration, respectively. Ech A treatment also inhibited inflammatory-response-induced mast cell infiltration in AD-like skin lesions and suppressed the expression of proinflammatory cytokines, such as interferon-γ, interleukin-4, and interleukin-13. Collectively, these results suggest that Ech A may be beneficial for treating AD owing to its anti-inflammatory effects.
Figure 1. Changes in 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like symptoms in the dorsal skin lesions of the mouse model. (A) Structure of echinochrome A (Ech A); (B) overall schematic diagram and timeline of experiments. NC/Nga mice were divided into six groups: nontreated (N), DNCB (D), DNCB + PBS topical application (PT), DNCB + PBS intraperitoneal (IP) injection (PI), DNCB + (Ech A) topical application (ET), and DNCB + Ech A IP injection (EI). (C) AD-like dorsal skin lesions were observed by dermoscopy every 2 weeks.
Figure 2. Histopathological images showing how Ech A improves the condition of damaged epidermis in DNCB-induced AD-like lesions in NC/Nga mice. (A) Skin sections were stained with hematoxylin and eosin (H&E) for the measurement of epidermal thickness in the DNCB-induced AD mouse model; (B) the thickness of the epidermis was measured with a NanoZoomer. The data shown in the graphs represent the mean ± SEM. *** p < 0.001, * p < 0.05. Scale bar = 100 μm.
Figure 3. Effect of Ech A on transepidermal water loss (TEWL) and stratum corneum hydration (SCH) scores in DNCB-induced AD-like NC/Nga mice. (A) Levels of TEWL in the skin epidermis were evaluated every 2 weeks through Tewameter® measurements; (B) SCH score was determined through Corneometer® measurements every 2 weeks in the DNCB-induced skin lesions. The data shown in the graphs represent the mean ± SEM (n = 6). *** p < 0.001, * p < 0.05.
Figure 4. Ech A reduces mast cell infiltration in AD-like NC/Nga mice. (A) Histological observation of toluidine-blue-stained samples showed reduced infiltration of mast cells in the ET and EI groups compared with the DNCB-treated groups; (B) the number of infiltrated mast cells was counted in five representative high-power fields by means of a NanoZoomer (n = 6). The data shown in the graphs represent the mean ± SEM. *** p < 0.001. Scale bar = 100 μm.
Figure 5. Ech A treatment showed an anti-inflammatory effect in the DNCB-induced AD-like mouse model. (A) Immunoblot analysis of protein expression related to proinflammation; (BâD) relative band intensity of skin interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-13 (IL-13) in AD-like skin lesions assessed through analysis with ImageJ. β-actin served as an internal standard; (E) scheme of the suppression mechanism of Ech A treatment in AD-like skin lesions. The data shown in the graphs represent the mean ± SEM of three independent experiments. * p < 0.05.
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