Anti-Atopic Dermatitis Effect of Azalomycin F on 2,4-Dinitrofluorobenzene-Induced Mice and Potential Mechanism

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Dec 17

PMID 39684557

Authors

Wenjia Zhao

Jianping Zhu

Xinrong Luo

Fengxian Lian

Yanli Yang

Su He

Jinzhou Zhu

Ganjun Yuan

Affiliations

Soon will be listed here.

Abstract

Azalomycin F (AZF) is a kind of antibiotic with antifungal and antibacterial activities, as well as anti-inflammatory and anti-tumor activities. In this study, we evaluated the effects of AZF on atopic dermatitis (AD) and its possible molecular mechanisms. Mice with 2,4-dinitrofluorobenzene-induced AD-like skin lesions were topically treated with 10-30 mg/kg AZF on their dorsal skin for 12 days. Observations focused on skin lesion scores, the frequency of scratching, and histopathological alterations in the skin. In addition, IgE and inflammatory cytokine levels in serum were assessed. The results indicated that topical application of 10-20 mg/kg AZF could reduce skin lesion scores and scratching frequencies in AD mice, while 15-20 mg/kg AZF decreased epidermal thickness and mast cell infiltration. Additionally, the serum levels of IgE, IFN-γ, IL-4, TSLP and IL-1β were reduced with 10-20 mg/kg AZF treatment. Moreover, RNA-Seq was employed to reveal the potential molecular mechanisms underlying anti-AD effects of AZF. KEGG enrichment analysis revealed that the most significantly differentially expressed genes are predominantly enriched in signaling pathways such as NF-κB and TNF. Protein-protein interaction network analysis identifies the key genes including Il1b, Tnf, and Cxcl1. In summary, 15 mg/kg AZF effectively alleviates the inflammatory response in AD mice, and the potential mechanism may involve the regulation of key signaling pathways like NF-κB and TNF, thereby reducing inflammatory factor levels and eliciting an anti-inflammatory effect. These findings provide valuable scientific evidence for the development of novel natural drugs for the treatment of AD.

References

Yamaguchi H, Yamaguchi Y, Peeva E . Role of Innate Immunity in Allergic Contact Dermatitis: An Update. Int J Mol Sci. 2023; 24(16). PMC: 10455292. DOI: 10.3390/ijms241612975. View

Liu F, Goodarzi H, Chen H . IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011; 41(3):298-310. DOI: 10.1007/s12016-011-8252-4. View

Zheng B, Wang B, Xiao W, Sun Y, Yang C, Zhao B . Different molecular weight hyaluronic acid alleviates inflammation response in DNFB-induced mice atopic dermatitis and LPS-induced RAW 264.7 cells. Life Sci. 2022; 301:120591. DOI: 10.1016/j.lfs.2022.120591. View

Yang G, Seok J, Kang H, Cho Y, Lee H, Lee J . Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis. Int J Mol Sci. 2020; 21(8). PMC: 7215310. DOI: 10.3390/ijms21082867. View

Xiong X, Huang C, Wang F, Dong J, Zhang D, Jiang J . Qingxue jiedu formulation ameliorated DNFB-induced atopic dermatitis by inhibiting STAT3/MAPK/NF-κB signaling pathways. J Ethnopharmacol. 2021; 270:113773. DOI: 10.1016/j.jep.2020.113773. View

Langan S, Irvine A, Weidinger S . Atopic dermatitis. Lancet. 2020; 396(10247):345-360. DOI: 10.1016/S0140-6736(20)31286-1. View

Cai R, Gong X, Li X, Jiang Y, Deng S, Tang J . Dectin-1 aggravates neutrophil inflammation through caspase-11/4-mediated macrophage pyroptosis in asthma. Respir Res. 2024; 25(1):119. PMC: 10921740. DOI: 10.1186/s12931-024-02743-z. View

Scibiorek M, Mthembu N, Mangali S, Ngomti A, Ikwegbue P, Brombacher F . IL-4Rα signalling in B cells and T cells play differential roles in acute and chronic atopic dermatitis. Sci Rep. 2023; 13(1):144. PMC: 9812985. DOI: 10.1038/s41598-022-26637-6. View

Tian T, Chang H, He K, Ni Y, Li C, Hou M . Fucoidan from seaweed Fucus vesiculosus inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis. Int Immunopharmacol. 2019; 75:105823. DOI: 10.1016/j.intimp.2019.105823. View

10.

Son Y, Yang W, Park S, Yang J, Kim S, Lyu J . The Anti-Inflammatory and Skin Barrier Function Recovery Effects of in Mice with Atopic Dermatitis. Medicina (Kaunas). 2023; 59(7). PMC: 10385087. DOI: 10.3390/medicina59071353. View

11.

Weidinger S, Beck L, Bieber T, Kabashima K, Irvine A . Atopic dermatitis. Nat Rev Dis Primers. 2018; 4(1):1. DOI: 10.1038/s41572-018-0001-z. View

12.

He S, Zhao W, Li P, Tu W, Hong K, Zhang D . Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats. Molecules. 2021; 26(21). PMC: 8588360. DOI: 10.3390/molecules26216464. View

13.

Zhao W, Zhang Y, Li W, Hu Q, Huang H, Xu X . Probiotic-fermented Portulaca oleracea L. alleviated DNFB-induced atopic dermatitis by inhibiting the NF-κB signaling pathway. J Ethnopharmacol. 2023; 313:116613. DOI: 10.1016/j.jep.2023.116613. View

14.

Lesiak A, Smolewski P, Sobolewska-Sztychny D, Sysa-Jedrzejowska A, Narbutt J . The role of T-regulatory cells and Toll-like receptors 2 and 4 in atopic dermatitis. Scand J Immunol. 2012; 76(4):405-10. DOI: 10.1111/j.1365-3083.2012.02739.x. View

15.

Li H, Zhang Z, Zhang H, Guo Y, Yao Z . Update on the Pathogenesis and Therapy of Atopic Dermatitis. Clin Rev Allergy Immunol. 2021; 61(3):324-338. DOI: 10.1007/s12016-021-08880-3. View

16.

Lee Y, Ryu H, Yang W, Park M, Park Y, Kim D . A combination of Olea europaea leaf extract and Spirodela polyrhiza extract alleviates atopic dermatitis by modulating immune balance and skin barrier function in a 1-chloro-2,4-dinitrobenzene-induced murine model. Phytomedicine. 2021; 82:153407. DOI: 10.1016/j.phymed.2020.153407. View

17.

Fyhrquist N, Muirhead G, Prast-Nielsen S, Jeanmougin M, Olah P, Skoog T . Microbe-host interplay in atopic dermatitis and psoriasis. Nat Commun. 2019; 10(1):4703. PMC: 6795799. DOI: 10.1038/s41467-019-12253-y. View

18.

Lan J, Song Z, Miao X, Li H, Li Y, Dong L . Skin damage among health care workers managing coronavirus disease-2019. J Am Acad Dermatol. 2020; 82(5):1215-1216. PMC: 7194538. DOI: 10.1016/j.jaad.2020.03.014. View

19.

Zhang J, Xu X, Wang X, Zhang L, Hu M, Le Y . Topical emollient prevents the development of atopic dermatitis and atopic march in mice. Exp Dermatol. 2023; 32(7):1007-1015. DOI: 10.1111/exd.14806. View

20.

Haddad E, Cyr S, Arima K, McDonald R, Levit N, Nestle F . Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis. Dermatol Ther (Heidelb). 2022; 12(7):1501-1533. PMC: 9276864. DOI: 10.1007/s13555-022-00737-7. View