Systems pharmacology reveals the mechanism of activity ofPhysalis alkekengiL. var.franchetiiagainst lipopolysaccharide‐induced acute lung injury

Autor: Zunpeng Shu, Xiaobo Sun, Bing-You Yang, Renxing Zhong, Yanlin Feng, Zihe Ding, Yi Wang, Yanni Yang, Yuanyuan Xie, Tianyi Xia
Rok vydání: 2020
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
Magnetic Resonance Spectroscopy
Physalis
Lipopolysaccharide
Chemistry
Pharmaceutical
Apoptosis
Pharmacology
medicine.disease_cause
Antioxidants
Mice
chemistry.chemical_compound
0302 clinical medicine
Physalis alkekengi L. var. franchetii
oxidative stress
Medicine
Chinese Traditional
Mice
Inbred BALB C
TUNEL assay
Lung Injury
respiratory system
Treatment Outcome
030220 oncology & carcinogenesis
Molecular Medicine
Original Article
medicine.symptom
systems pharmacology
Signal Transduction
NF-E2-Related Factor 2
Acute Lung Injury
Inflammation
Lung injury
Sepsis
03 medical and health sciences
Metabolome
medicine
Animals
Metabolomics
Plant Extracts
business.industry
Original Articles
Cell Biology
medicine.disease
030104 developmental biology
chemistry
Multivariate Analysis
business
Oxidative stress
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.15126
Popis: Acute lung injury (ALI) is an important cause of mortality of patients with sepsis, shock, trauma, pneumonia, multiple transfusions and pancreatitis. Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF) has been extensively used in Chinese folk medicine because of a good therapeutic effect in respiratory diseases. Here, an integrated approach combining network pharmacology, proton nuclear magnetic resonance‐based metabolomics, histopathological analysis and biochemical assays was used to elucidate the mechanism of PAF against ALI induced by lipopolysaccharide (LPS) in a mouse model. We found that the compounds present in PAF interact with 32 targets to effectively improve the damage in the lung undergoing ALI. We predicted the putative signalling pathway involved by using the network pharmacology and then used the orthogonal signal correction partial least‐squares discriminant analysis to analyse the disturbances in the serum metabolome in mouse. We also used ELISA, RT‐qPCR, Western blotting, immunohistochemistry and TUNEL assay to confirm the potential signalling pathways involved. We found that PAF reduced the release of cytokines, such as TNF‐α, and the accumulation of oxidation products; decreased the levels of NF‐κB, p‐p38, ERK, JNK, p53, caspase‐3 and COX‐2; and enhanced the translocation of Nrf2 from the cytoplasm to the nucleus. Collectively, PAF significantly reduced oxidative stress injury and inflammation, at the same time correcting the energy metabolism imbalance caused by ALI, increasing the amount of antioxidant‐related metabolites and reducing the apoptosis of lung cells. These observations suggest that PAF may be an effective candidate preparation alleviating ALI.
Databáze: OpenAIRE
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