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DNFB
Journal of Functional Foods · 2020 · IF 3.701

Ameliorative effect of orally administered different linoleic acid/α-linolenic acid ratios in a mouse model of DNFB-induced atopic dermatitis

Liu Tang,Xiaolei Li,Liping Wan,Huiling Wang,Qianting Mai,Zixin Deng,Hong Ding

The present research was designed to evaluate the protective effects and underlying mechanisms of different ratios of linoleic acid (LA) and α-linolenic acid (ALA), two essential polyunsaturated fatty acids (PUFAs) fatty acids, on atopic dermatitis (AD)-like skin lesions induced by 2, 4-dinitrofluorobenzene (DNFB). The dorsal flank and ear pinnas of mice were sensitized and challenged with DNFB for four weeks in order to establish AD model. Simultaneously, the mice were orally administered different ratios of LA/ALA (v/v; 4:1 or 1:1), or dexamethasone (Dex; 0.1 mg/kg). Results showed that different LA/ALA ratios, especially a ratio of 4:1 treatment, could effectively ameliorate DNFB-induced skin lesions, ear edema, scratching behavior and skin inflammation, as reflected by the reduced inflammatory blood cells, IgE serum levels, and skin levels of the pro-inflammatory lipid mediators, including PGE 2 and LTB 4 . These findings were further confirmed by skin pathological examination. Moreover, LA/ALA administration markedly suppressed the proliferation and infiltration of T cells, the production of T helper cell type 1 (Th1), Th2 and Th17 cytokines in dorsal skin and serum of DNFB-treated mice. Western blotting and immunohistochemistry staining revealed that LA/ALA downregulated the protein expressions of JAK2 and STAT4, and thus reducing the synthesis of type Th1 cytokine IFN-γ. Taken together, these results suggest that optimal nutrition ratio of LA/ALA has beneficial effects on AD-like symptoms, which provide theoretical basis for its therapeutic potential in the clinical prevention and treatment of AD.

研究领域: 免疫学 · 营养学 · 皮肤病学
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2022 · IF 5.714

Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROS-mediated JAK2/STAT5 signaling pathway

Jie-Fang Gao,Liu Tang,Fei Luo,Yi-Yuan Zhang,Lu Chen,Hong Ding,Zu-Dong Meng

Background and purpose Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritus and impaired skin barrier function. The pathology of AD involves in immune dysfunction and epidermal barrier disruption. Reactive oxygen species (ROS) are found to be associated with AD, and play a role in the immunological abnormalities and dysfunctional skin barrier. Nicotinamide mononucleotide (NMN) plays an important role in oxidative stress related diseases, but its role in AD is unclear. Methods KM mice were treated with DNFB to induce AD-like lesion and typical applied with NMN for two weeks. The dermatitis score, the degree of itching and TEWL were evaluated during modeling. Epidermal thickness of skin lesions and histopathological changes were detected. Further, inflammatory factors, epidermal differentiation-related genes, oxidative stress indicators and JAK2/STAT5 signaling pathway were evaluated. NHEK cells were stimulated by TNF-α/IFN-γ after pre-treatment with NMN, then ROS levels, inflammatory factors and JAK2/STAT5 signaling pathway were detected. Results NMN exhibited potent anti-atopic activities, shown by alleviated AD-like symptoms, inhibited the increased expression of inflammatory cytokines and restored proteins and mRNA level of skin barrier genes. In addition, NMN inhibited TNF-α/IFN-γ-stimulated elevation of inflammatory chemokines, which was associated with blocking the activation of ROS-mediated JAK2/STAT5 pathway. Conclusion NMN may have a positive effect on relieving symptoms of AD.

CAS / MDL: 8001-25-0
研究领域: 皮肤病学 · 免疫学 · 药理学 · 分子生物学
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Journal of Inflammation Research · 2026 · IF 4.6

Gut Microbiota Mitigates Chronic Itch and Cutaneous Inflammation in DNFB-Induced Atopic Dermatitis Mice

Zichen Xiong,Xinming Dong,Yi Yuan,Lin Lu,Xueting Deng

Background Chronic itch is the most prominent symptom of atopic dermatitis (AD), which severely impacts the quality of life of patients and persists even after medication. Gut microbiota dysbiosis is considered to contribute to AD, however, the roles of gut microbiota in the modulation of chronic pruriceptive processing currently remain unclear. The present study aimed to elucidate the potential regulatory role of the gut microbiota in AD-associated chronic itch.Methods In this study, the 1-fluoro-2,4-dinitrobenzene (DNFB)-induced mouse model of AD-associated chronic itch was established. Differences in gut microbiota composition between model and healthy controls were analyzed using high-throughput 16S rRNA gene sequencing. In addition, we performed oral fecal microbiota transplantation (FMT) from model mice to antibiotic cocktail-treated healthy mice and observed whether they could induce itch behavior. Furthermore, feces from healthy mice were transplanted into model mice to evaluate their effects on itch symptoms and skin inflammation.Results The DNFB induced significantly itch behaviors and an altered gut microbiota composition. The gut microbiota from chronic itch mice through oral administration could induce itch behaviors in antibiotic cocktail-treated healthy mice. While, oral FMT from healthy mice to chronic itch mice not only significantly alleviated scratching behavior but also ameliorated skin damage and inflammation. Following FMT administration from healthy donors, remarkable alterations were observed in the metabolomic profiles of mice with DNFB-induced chronic itch.Conclusion These findings highlight the potential link between gut microbiota dysbiosis and chronic itching in AD, suggesting that targeting the gut microbiota may be a therapeutic strategy for chronic itch.

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TOXICOLOGICAL SCIENCES · 2022 ·Vol. 191 ·期 2 ·308-320 · IF 4.109

Myricetin treatment has ameliorative effects in DNFB-induced atopic dermatitis mice under high-fat conditions

Gao Jie-Fang,Tang Liu,Luo Fei,Chen Lu,Zhang Yi-Yuan,Ding Hong

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disorder. Obesity is associated with increased prevalence and severity of AD for reasons that remain poorly understood. Myricetin, a dietary flavonoid found in fruits and vegetables, is known to have anti-inflammatory effects, but its role in AD is unclear. Thus, we investigated the effects of obesity on exacerbation AD lesions and evaluated the effects of myricetin on obese AD. Mice were fed normal diet (ND) or high-fat diet, and then 2,4-dinitrofluorobenzene was used to induce AD-like lesions. We found that obesity exacerbated AD lesions, and myricetin topical administration ameliorated symptoms and skin lesions of obsess AD mice, such as dermatitis scores, scratching behavior, epidermal thickness, and mast cell infiltration. In addition, myricetin reduced the levels of immunoglobulin E and histamine, inhibited the infiltration of CD4+T cells, and modulated the expression of Th1, Th2, Th17, and Th22 cytokines and pro-inflammatory factors (CCL17, CCL22, IL-1β, and TGF-β). Moreover, myricetin restored impaired barrier function by reducing transepidermal water loss, increasing lamellar body secretion, as well as upregulating the mRNA and protein expression of filaggrin. Western blot results showed that significantly increased levels of phosphorylated IκB and NF-κB p65 was observed in the obese AD mice compared with the AD mice fed ND, whereas the myricetin could downregulated the phosphorylations of IκB and NF-κB, and inhibited mRNA expression of iNOS and COX2. Taken together, our results suggest that myricetin treatment exhibits potentially protective effects against the obeseassociated AD by inhibiting inflammatory response and restoring skin barrier function.

CAS / MDL: 529-44-2 8001-25-0
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Biomed Research International · 2021 · IF 3.411

Topical Applications of a Novel Emollient Inhibit Inflammation in Murine Models of Acute Contact Dermatitis

Si Wen,Mengke Sun,Li Ye,Bin Yang,Lizhi Hu,Mao-Qiang Man

The benefits of emollients for eczematous dermatitis and psoriasis have been thought to be due to the improvements in epidermal function, including epidermal permeability barrier, stratum corneum hydration, and stratum corneum pH. We determined here whether emollient can direct inhibit cutaneous inflammation. Ear inflammation was induced by topical application of either 12-O-tetradecanoylphorbol-13-acetate (TPA) or 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Either 1% hydrocortisone cream or the novel emollient was applied to the right ear of the mice 45 min and 2 hours after TPA or DNFB application. The untreated left ear served as untreated controls. Both ear weight and ear thickness were measured 24 hours after TPA and DNFB application. Topical applications of either hydrocortisone cream or emollient significantly decreased both ear thickness and ear weight in comparison to untreated controls. In DNFB model, hydrocortisone significantly lowered expression levels of mRNA for IL-1α, IL-1β, and TNFα, while the emollient markedly decreased expression levels of IL-1α and TNFα mRNA. In TPA model, both hydrocortisone and emollient significantly decreased expression levels of IL-1α, IL-1β, IL-6, and TNFα mRNA. In parallel, inflammatory infiltration was also reduced by topical applications of either hydrocortisone or emollient. These results demonstrate that this novel emollient can directly inhibit cutaneous inflammation in murine models of both acute irritant contact dermatitis and acute allergic contact dermatitis. However, whether this emollient could also alleviate eczematous dermatitis in humans remains to be explored.

CAS / MDL: 70-34-8
研究领域: 皮肤病学 · 免疫学 · 药理学
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