Mechanism of Qilongtian Capsules in treatment of acute lung injury based on network pharmacology prediction and experimental validation.
10.19540/j.cnki.cjcmm.20230510.703
- Author:
Ying XIE
1
;
Xue-Rong SU
1
;
Tong ZHOU
1
;
Yi-Yao LIANG
1
;
Yang-Qian WU
1
;
Yi WAN
1
;
Tu-Lin LU
1
;
Xiao-Li ZHAO
1
;
Zheng-Yan LI
2
Author Information
1. School of Pharmacy,Nanjing University of Chinese Medicine Nanjing 210046, China.
2. Kunming Municipal Hospital of Chinese Medicine Kunming 650051,China.
- Publication Type:Journal Article
- Keywords:
Qilongtian Capsules;
UPLC-Q-TOF-MS/MS;
acute lung injury;
macrophage RAW264.7;
molecular docking;
network pharmacology
- MeSH:
Humans;
Tumor Necrosis Factor-alpha;
Ginsenosides;
Caspase 3;
Matrix Metalloproteinase 9;
Interleukin-6;
Molecular Docking Simulation;
Network Pharmacology;
Reactive Oxygen Species;
Tandem Mass Spectrometry;
Acute Lung Injury/genetics*;
Capsules;
RNA, Messenger;
Drugs, Chinese Herbal/pharmacology*
- From:
China Journal of Chinese Materia Medica
2023;48(15):4187-4200
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1β, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1β, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.
