Huangbai Liniment Ameliorates Skin Inflammation in Atopic Dermatitis

Ting Zheng; Miao Fan; Yunbo Wei; Jinhong Feng; Pengcheng Zhou; Xin Sun; Anqi Xue; Cheng Xue Qin; Di Yu

doi:10.3389/fphar.2021.726035

Huangbai Liniment Ameliorates Skin Inflammation in Atopic Dermatitis

Front Pharmacol. 2021 Aug 31:12:726035. doi: 10.3389/fphar.2021.726035. eCollection 2021.

Authors

Ting Zheng^{1

2}, Miao Fan³, Yunbo Wei^{1

2}, Jinhong Feng^{1

2}, Pengcheng Zhou⁴, Xin Sun⁵, Anqi Xue^{1

2}, Cheng Xue Qin^{3

6

7}, Di Yu^{1

4}

Affiliations

¹ Shandong Analysis and Test Center, Laboratory of Immunology for Environment and Health, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
² School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
³ School of Pharmaceutical Science, Shandong University, Jinan, China.
⁴ The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
⁵ School of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
⁶ Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁷ Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.

Abstract

Atopic dermatitis (AD), also known as atopic eczema, is one of the most common skin diseases and is characterized by allergic skin inflammation, redness, and itchiness and is associated with a hyperactivated type 2 immune response. The leading causes of AD include an imbalance in the immune system, genetic predisposition, or environmental factors, making the development of effective pharmacotherapies complex. Steroids are widely used to treat AD; however, they provide limited efficacy in the long term and can lead to adverse effects. Thus, novel treatments that offer durable efficacy and fewer side effects are urgently needed. Here, we investigated the therapeutic potential of Huangbai Liniment (HB), a traditional Chinese medicine, using an experimental AD mouse model, following our clinical observations of AD patients. In both AD patient and the mouse disease model, HB significantly improved the disease condition. Specifically, patients who received HB treatment on local skin lesions (3-4 times/day) showed improved resolution of inflammation. Using the 1-Chloro-2,4-dinitrobenzene (DNCB)-induced AD model in BALB/c mice, we observed that HB profoundly alleviated severe skin inflammation and relieved the itching. The dermatopathological results showed markedly reversed skin inflammation with decreased epidermal thickness and overall cellularity. Correspondingly, HB treatment largely decreased the mRNA expression of proinflammatory cytokines, including IL-1β, TNF-α, IL-17, IL-4, and IL-13, associated with declined gene expression of IL-33, ST2, and GATA3, which are connected to the type 2 immune response. In addition, HB restored immune tolerance by promoting regulatory T (T_REG) cells and inhibiting the generation of T_H1, T_H2, and T_H17 cells in vitro and in the DNCB-induced AD mouse model. For the first time, we demonstrate that HB markedly mitigates skin inflammation in AD patients and the DNCB-induced AD mouse model by reinvigorating the T cell immune balance, shedding light on the future development and application of novel HB-based therapeutics for AD.

Keywords: CD4 T cells; atopic dermatitis; huangbai liniment (HB); immunomodulation; regulatory T (treg) cell.