The Mechanism Underlying Hanchuanshu Treatment of Asthma Based on Network Pharmacology and Biological Verification of The Effects in Smooth Muscle Cells: OAJBS Publishers
The
Mechanism Underlying Hanchuanshu Treatment of Asthma Based on Network
Pharmacology and Biological Verification of The Effects in Smooth Muscle Cells
by Zhiyong Liu* in Open Access Journal of
Biomedical Science (OAJBS)
Objective: To construct a molecular regulatory
network of “components-core targets of smooth muscle action-pathways” for the
treatment of asthma by Hanchuanshu. This model was used to explore the
mechanism of its “multiple components-multiple targets-multiple pathways”
network. Rat airway smooth muscle cells (ASMCs) were cultured in vitro, and the
effect of Hanchuanshu on the cytokine expression of contractile and synthetic
ASMCs was explored.
Methods: The ADME/T calculation method was used
to screen the components of Hanchuanshu for the treatment of asthma. Through
network pharmacology methods, the target identification platform based on
reverse pharmacophore matching was used to analyze. Predict potential targets,
and a biological annotation database (DAVID) was used to analyze the function
of target genes and metabolic pathways. Cytoscape software was used to
construct a network model of “components-core targets of smooth muscle
action-pathways” for the treatment of asthma with Hanchuanshu. Rat ASMCs were cultured
in vitro, and ASMCs were exposed to final concentrations of 1, 2, and 4 μg/ml
for 48h. The RT-qPCR method was used to determine the mRNA levels of ADRB1,
a-SMA, IL-6, TNF-α, IFN-γ, IL-4 and IL-10.
Results: The results of network analysis showed
that the 63 active ingredients in Hanchuanshu may regulate the TNF signaling
pathway, phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) signaling
pathway, HIF-1, and 132 pathways, such as FAK, calcium, and Ras, which play a
role in treating asthma. Through in vitro cytological simulation of the two
phenotypes of asthmatic airway smooth muscle cells, it was found that
Hanchuanshu can increase the expression of ADRB1 in contractile ASMCs and has
little effect on the expression of a-SMA and IL-4; in contrast, it increased
the expression of ADRB1, a-SMA, IL-10 and IFN-γ in synthetic ASMCs and
decreased the expression of IL-4, IL-6 and TNF-α.
Conclusion: A network pharmacology analysis found
that Hanchuanshu has multiple active components, multiple targets and multiple
pathways in smooth muscle cells in the treatment of asthma, providing new ideas
and clues for the elaboration of the mechanism of this compound. In vitro
experiments verified that Hanchuanshu can inhibit the expression of IL-4, IL-6
and TNF-α and promote the expression of ADRB1, a-SMA, IL-10 and IFN-γ in ASMCs
to exert an anti-asthma effect.
https://biomedscis.com/fulltext/the-mechanism-underlying-hanchuanshu-treatment-of-asthma-based-on-network-pharmacology.ID.000278.php
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