Affiliation:
1. Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, China
2. College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China.
3. College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
4. Department of
Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, China
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.
Funder
Natural Science Foundation of China
Zhejiang Provincial Medical and Health Science and Technology Plan Project
Shenyang Young and Middle-aged Science and Technology Innovation talents support Program
Liaoning University Innovation Talent Support Program
Taizhou Science and Technology Plan project
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Computer Science Applications,Drug Discovery,General Medicine