Integrating network pharmacology, experimental validation and molecular docking to reveal the alleviation of Yinhuang granule on idiopathic pulmonary fibrosis

Zeqi Wu; Ruijia Shi; Shihao Yan; Shaobo Zhang; Bin Lu; Zhenlin Huang; Lili Ji

doi:10.1016/j.phymed.2024.155368

Integrating network pharmacology, experimental validation and molecular docking to reveal the alleviation of Yinhuang granule on idiopathic pulmonary fibrosis

Phytomedicine. 2024 Jun:128:155368. doi: 10.1016/j.phymed.2024.155368. Epub 2024 Jan 17.

Authors

Zeqi Wu¹, Ruijia Shi², Shihao Yan³, Shaobo Zhang¹, Bin Lu¹, Zhenlin Huang⁴, Lili Ji⁵

Affiliations

¹ The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
² School of Basic Medical Science of Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
³ The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Pharmacy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai,200123, China.
⁴ The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: zhenlin_huang@shutcm.edu.cn.
⁵ The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: jilili@shutcm.edu.cn.

PMID: 38498951
DOI: 10.1016/j.phymed.2024.155368

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by the abnormal proliferation of fibroblast and excessive deposition of extracellular matrix (ECM), accompanied by inflammation and ultimately respiratory failure. Yinhuang granule (YHG), with clinical properties of clearing heat, detoxifying and anti-inflammation, is commonly used to heal upper respiratory diseases in China for decades.

Purpose: To explore the improvement of YHG on bleomycin (BLM)-induced IPF in mice and its possible engaged mechanism.

Methods: The mortality rate was recorded, lung function was determined and hematoxylin-eosin (H&E) staining was carried out to explore the alleviation of YHG on BLM-caused IPF in mice. Hydroxyproline, collagen I and collagen III contents were detected, and Sirius red and Masson staining were conducted to evaluate YHG's alleviation on lung fibrosis. The underlying mechanism was predicted by network pharmacology, and confirmed by Real-time polymerase chain reaction (RT-PCR), Western-blot (WB) and enzyme linked immunosorbent assay (ELISA). The binding affinity between related key proteins and active compounds in YHG was calculated by using molecular docking, and further validated by cellular thermal shift assay (CESTA).

Results: YHG (400, 800 mg/kg) weakened lung damage and pulmonary fibrosis in mice induced by BLM. Network pharmacology and experimental validation displayed that inflammation and angiogenesis participated in the YHG-provided improvement on IPF, and key involved molecules included tumor necrosis factor-α (TNFα), vascular endothelial growth factor-A (VEGFA), interleukine-6 (IL-6), etc. The data of molecular docking presented that some main active compounds from YHG had a high binding affinity with TNFR1 or VEGFR2, and some of them were further validated by CESTA.

Conclusion: YHG effectively improved the BLM-induced IPF in mice via reducing inflammation and angiogenesis.

Keywords: IPF; Molecular docking; Network pharmacology; YHG.

MeSH terms

Animals
Bleomycin*
Disease Models, Animal
Drugs, Chinese Herbal* / chemistry
Drugs, Chinese Herbal* / pharmacology
Humans
Idiopathic Pulmonary Fibrosis* / chemically induced
Idiopathic Pulmonary Fibrosis* / drug therapy
Lung / drug effects
Male
Mice
Mice, Inbred C57BL
Molecular Docking Simulation*
Network Pharmacology*
Tumor Necrosis Factor-alpha / metabolism
Vascular Endothelial Growth Factor A* / metabolism

Substances

Drugs, Chinese Herbal
Bleomycin
Vascular Endothelial Growth Factor A
Tumor Necrosis Factor-alpha