"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation.
10.19540/j.cnki.cjcmm.20220920.401
- Author:
Hong-Ying CHEN
1
;
Peng-Fei YAO
2
;
Yan-Qi HAN
3
;
Xu XU
3
;
Jun XU
3
;
Bi-Yan PAN
4
;
Dong-Sheng OUYANG
5
;
Tie-Jun ZHANG
3
Author Information
1. Department of Clinical Pharmacology,Xiangya Hospital,Central South University Changsha 410008,China Guangzhou Baiyunshan Mingxing Pharmaceutical Co.,Ltd. Guangzhou 510250,China.
2. Tianjin University of Traditional Chinese Medicine Tianjin 301617,China.
3. Tianjin Key Laboratory of Quality Marker of Traditional Chinese Medicine,Tianjin Institute of Pharmaceutical Research Tianjin 300301,China.
4. Guangzhou Baiyunshan Mingxing Pharmaceutical Co.,Ltd. Guangzhou 510250,China.
5. Department of Clinical Pharmacology,Xiangya Hospital,Central South University Changsha 410008,China.
- Publication Type:Journal Article
- Keywords:
"component-target-efficacy";
Qingkailing Oral Preparation;
mechanism;
molecular docking;
network pharmacology;
pharmacodynamic substances
- MeSH:
Chlorogenic Acid;
Drugs, Chinese Herbal/pharmacology*;
gamma-Aminobutyric Acid;
Interleukin-6;
Medicine, Chinese Traditional;
Molecular Docking Simulation;
Tumor Necrosis Factor-alpha/genetics*;
Animals;
Mice;
RAW 264.7 Cells
- From:
China Journal of Chinese Materia Medica
2023;48(1):170-182
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.
