Shikonin modulates activated fibroblast apoptosis in silicosis fibrosis via the PI3K/Akt signaling pathway: A network pharmacology approach

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-02-01 DOI:10.1016/j.taap.2025.117236

Shengpeng Wen , Sirong Chang , Huning Zhang , Wenyue Zhang , Yi Guo , Na Zhang , Anning Yang , Yue Sun , Zhihong Liu

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引用次数: 0

Abstract

Background

Silicosis is a lung disease caused by the inhalation of free crystalline silica and is characterized mainly by lung inflammation and progressive pulmonary fibrosis. Shikonin, a biologically active compound isolated from the traditional Chinese medicine Comfrey, has been shown to have significant antifibrotic effects. However, the molecular mechanisms underlying the antifibrotic effects of SHK in silicosis remain unclear.

Methods

This study used a combination of network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experimental validation to investigate the potential targets of SHK in silicosis.

Results

Network pharmacology analysis identified 208 cross genes associated with disease drugs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis show that these intersecting genes are significantly associated with the PI3K/Akt signaling pathway. Protein protein interaction (PPI) network analysis further revealed 10 core crossover genes, namely ALB, Akt1, STAT3, CASP3, EGFR, MMP9, Bcl-2, ESR1, HSP90AA1, and NF-κB1. Among them, Akt1 and Bcl-2 have the strongest binding ability to SHK. The in vitro experimental results showed that SHK can significantly inhibit the activation of fibroblasts and promote apoptosis of activated fibroblasts through the PI3K/Akt signaling pathway.

Conclusion

SHK alleviates silica induced silicosis fibrosis by inhibiting the transformation of fibroblasts into myofibroblasts through the PI3K/Akt signaling pathway.

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.