2. Academic Validation
  3. Calycosin enhances Treg differentiation for alleviating skin inflammation in atopic dermatitis

Calycosin enhances Treg differentiation for alleviating skin inflammation in atopic dermatitis

  • J Ethnopharmacol. 2024 Feb 7:326:117883. doi: 10.1016/j.jep.2024.117883.
Xin Ma 1,  Guoshu Deng 2,  Na Tian 3,  Hao Wang 4,  Hang Zhao 5,  Le Kuai 6,  Ying Luo 7,  Chunjie Gao 8,  Xiaojie Ding 9,  Bin Li 10,  Bin Li 11
Affiliations

Affiliations

  • 1 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China. Electronic address: nicole.ma@me.com.
  • 2 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: dluck0027@163.com.
  • 3 Department of Rheumatology and Immunology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. Electronic address: arrow_tn@163.com.
  • 4 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: whpfym@163.com.
  • 5 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: drhero1125@163.com.
  • 6 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: mjbubu@qq.com.
  • 7 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: 243601550@qq.com.
  • 8 Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China. Electronic address: chunjiegao@163.com.
  • 9 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: dingxiaojie1222@163.com.
  • 10 Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China. Electronic address: lib@shskin.com.
  • 11 Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Center for Immune-Related Diseases at Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 20025, China; Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20025, China; Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20025, China. Electronic address: binli@shsmu.edu.cn.
PMID: 38331120 DOI: 10.1016/j.jep.2024.117883
Abstract

Ethnopharmacological relevance: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder that poses a significant global health challenge. There is a lack of safe and effective medications to treat AD. Astragalus membranaceous is a traditional Chinese medicine widely used in clinical treatment of skin diseases. Calycosin (CA), derived from the root of Astragalus membranaceous, exhibits dual attributes of anti-inflammatory and antioxidant properties, suggesting its promise for addressing cutaneous inflammation. Nonetheless, the precise mechanisms underlying CA's therapeutic actions in AD remain elusive.

Aim of the study: This study aimed to evaluate the efficacy and safety of CA in treating AD while also delving into the mechanistic underpinnings of CA's action in AD.

Materials and methods: The cell viability and anti-inflammatory impacts of CA in vitro were first gauged using CCK-8 and RT-qPCR. The potential mechanisms of CA were then probed using modular pharmacology. Flow cytometry was employed to ascertain the differentiation of Treg and Th17 cells derived from naïve T cells, as well as the proportions and mean fluorescence intensity (MFI) of human iTreg cells. The expressions of IL-10 and TGF-β1 were measured and Treg suppression assay was performed. The in vivo therapeutic efficacy of topical CA application was assessed using a calcipotriol (MC903)-induced AD mouse model. The expression metrics of inflammatory cytokines, IL-17A, FOXP3, and RORγt were authenticated via immunohistochemistry, RT-qPCR, Western blot, and ELISA.

Results: CA exhibited a favorable safety profile and reduced the mRNA expressions of Th2 inflammatory cytokines in HaCaT cells. Modular pharmacology analysis pinpointed Th17 differentiation as the pivotal mechanism behind CA's therapeutic effect on AD. In vitro, CA fostered the differentiation of naïve T cells into Tregs while inhibiting their differentiation into Th17 cells. Furthermore, CA augmented the proliferation of human iTregs. In vivo, CA alleviated skin manifestations and decreased the levels of inflammatory mediators (IL-4, IL-5, IL-13, TSLP, and NF-κB related cytokines) in AD-like mouse models. Simultaneously, it regulated Treg/Th17 balance through suppressing IL-17A and RORγt expressions and bolstering FOXP3 expression.

Conclusions: The study provides insights into the mechanistic pathways through which CA exerts its anti-inflammatory effects, particularly through promoting Treg cell differentiation and inhibiting Th17 cell differentiation. Furthermore, CA emerges as an alternative or adjunctive treatment strategy for managing AD.

Keywords

Atopic dermatitis; Calycosin; Modular pharmacology; Skin inflammation; Th17; Tregs.

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