Exploring the Latent Mechanism of Huanglian Jiedu Decoction Formula
for Anti-atopic Dermatitis by Systems Pharmacology

Chang      Liu; Sheng      Shu; Zhelin      Xia; Guirong      Chen; Yubin      Xu

doi:10.2174/1386207325666220531091324

Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, which does not have a specific drug presently. Huanglian jiedu decoction (HJD) is one of the effective traditional Chinese medicine prescriptions. The real material and mechanisms of HJD for AD are not clear.

Objective: Network pharmacology and in vivo experiments were used to explore the real material and mechanisms of HJD for AD.

Methods: A systems’ pharmacology approach that provides a comprehensive analysis of bioactive compounds, targets, and pathway interactions was employed to elucidate the molecular pathogenesis of HJD for AD. First, the compound databases were constructed for HJD, and compound targets were predicted. Then, the hub targets of HJD were selected by degree centrality analysis and validated using the molecular docking method. Finally, Compound-Target and Target-Pathway networks were constructed to explore the latent mechanism of HJD for AD. Then, animal models of AD were established, the pathology of the skin lesions was observed, and RT-PCR and ELISA methods were used to verify the key targets in the serum of AD mice.

Results: The results showed that 60 bioactive compounds (palmatine, wogonin, cavidine, etc.) of HJD interacting with 169 related hub targets (PTGS2, HSP90AA1, etc.) were authenticated. HJD potentially participates in response to stimuli, biological regulation, and reproduction through the PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, and Fc epsilon RI signaling pathway, which are interrelated to the pathogenesis of AD. Compared with the control group, the thickening of the epidermis in the model group was obvious with inflammatory cells infiltrating, the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-α were up-regulated; and 6.4g/kg and 12.8g/kg HJD could significantly reduce the thickening of the epidermis and infiltration of inflammatory cells, down-regulate the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-α in the AD mice. HJD might exert its anti-AD effects by downregulating key indicators (PI3K, AKT, JNK, ERK, IL-4, and TNF-α) in the PI3K/AKT and MAPK pathways.

Conclusions: Our study could help us understand the compound and mechanism of HJD for AD. Moreover, it had a guidance function to change the traditional arrangement of formula for HJD.

Keywords: Atopic dermatitis, huanglian jiedu decoction, systems pharmacology, network, traditional chinese medicine, material basis.

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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1386207325666220531091324	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

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