Systems pharmacology unravels the synergic target space and therapeutic potential of Rhodiola rosea L. for non-small cell lung cancer

Zhang, Xia; Zhu, Jinglin; Yan, Jiangna; Xiao, Yue; Yang, Ruijie; Huang, Ruifei; Zhou, Jun; Wang, Zhenzhong; Xiao, Wei; Zheng, Chunli; Wang, Yonghua

doi:10.1016/j.phymed.2020.153326

Cited by 15 publications

(11 citation statements)

References 72 publications

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“…Traditional Chinese medicine (TCM) can detoxify and confer synergy in the prevention and treatment of diseases such as arthritis [16] and cancer [17] . However, there are few reports of TCM-based COPD therapies.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

Zhang

Chen

et al. 2021

Preprint

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PurposeJinwei decoction can enhance the anti-inflammatory effect of glucocorticoid (GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of HDAC2. But the upstream mechanism of Jinwei decoction on HDAC2 expression is not clear. ObjectiveTo explore whether Jinwei decoction can enhance the anti-inflammatory effect of GC on COPD through microRNA21 (miR-21) by network pharmacology. MethodsThe TCMSP database was used to screen active ingredients and target genes of Jinwei decoction, and miRWalk2.0 was used to predict downstream target genes of miR-21. COPD-related genes were identified by searching GeneCards and OMIM databases; Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software. Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core genes. Finally, interactions between main compounds and potential targets were verified by molecular docking. ResultsTwo hundred ninety-two active ingredients, 316 Jinwei drug targets, 10170 miR-21 target genes, 6617 COPD target genes, and 184 intersection gene were identified. Eleven core proteins of PPI networks may be involved. GO enrichment analysis showed that oxidative stress, regulation of inflammatory response, hormone transport, and histone modification were involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated protein kinase (MAPK), HIF-1, neutrophil extracellular bactericidal network, and other signaling pathways. ConclusionJinwei decoction can regulate histone deacetylase-2 activity and enhance the anti-inflammatory effect of GC on COPD by modulating miR-21. Its mechanism of action may be related to its effect on the PI3K Akt, MAPK, and TNF signaling pathways and neutrophil extracellular trap formation through miR-21.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

Zhang

Chen

et al. 2021

Preprint

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“…TCM is characterized by multi-component, multi-target integration and regulation. Thus, it is important for research to determine the active metabolites of drugs ( Zhang et al, 2020 ). In this study, we set out to use the UHPLC-QE-MS assay to determine the chemical composition of MMQ-8.…”

Section: Resultsmentioning

confidence: 99%

The Traditional Mongolian Medicine Qiqirigan-8 Effects on Lipid Metabolism and Inflammation in Obesity: Pharmacodynamic Evaluation and Relevant Metabolites

Narenmandula

Hongmei²,

Ding³

et al. 2022

Front. Pharmacol.

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Objective: Traditional Mongolian Medicine Qiqirigan-8 (MMQ-8) is a Chinese botanical drug with effective pharmacological properties in obesity. However, the pharmacological mechanism of MMQ-8 remains unclear. This study aimed to determine the active metabolites of MMQ-8 and its therapeutic effects on lipid metabolism and inflammation.Methods: The active metabolites of MMQ-8 were identified by ultrahigh-performance liquid chromatograph Q extractive mass spectrometry (UHPLC-QE-MS) assay and network analysis. An obesity rat model induced by high-fat diet was used in the study. Serum levels of lipids and inflammatory factors were detected using biochemical analysis and enzyme-linked immunosorbent assay (ELISA). Pathological analysis of liver tissues and arteries was conducted with hematoxylin and eosin (H&E) staining and immunohistochemistry. Protein expression of the tumor necrosis factor (TNF) signaling pathway was investigated by Western-blot. Simultaneously, bone marrow cells were used for RNA sequencing and relevant results were validated by cell culture and quantitative real-time polymerase chain reaction (RT-qPCR).Results: We identified 69 active metabolites and 551 target genes of MMQ-8. Of these, there are 65 active metabolites and 225 target genes closely related to obesity and inflammation. In vivo, we observed that MMQ-8 had general decreasing effects on body weight, white adipose tissue weight, and serum lipids. MMQ-8 treatment notably decreased the liver function markers and hepatic steatosis, and significantly decreased inflammation. In serum, it notably decreased TNF-α, interleukin (IL)-6, and inducible nitric oxide synthase (INOS), while elevating IL-10 levels. MMQ-8 treatment also significantly inhibited proteins phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα), mitogen-activated protein kinase (p38), extracellular regulated kinase 1/2(ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and decreased vascular endothelium damage and macrophage infiltration and polarization to M1. These findings coincide with the RNA-sequencing data of bone marrow cells and results of in vitro experiments.Conclusion: We determined the pharmacological actions and relevant metabolites of MMQ-8 in obesity for the first time. Our study revealed MMQ-8 can optimize lipid metabolism and reduce chronic inflammation in obesity. However, more in-depth research is needed, for example, to understand the principle of compound compatibility and the inhibition effects on hepatic steatosis, T cell differentiation, and inflammatory signal transduction.

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“…In this study, for the sake of verifying the molecular mechanisms of PRGRC in the treatment of gastric cancer, we constructed the C-T network and T-P network by Cytoscape3.6.0 55 . In networks, the compounds, targets and pathways were represented by nodes, and the interaction between nodes were represented by edges.…”

Section: Methodsmentioning

confidence: 99%

Systems pharmacology to reveal multi-scale mechanisms of traditional Chinese medicine for gastric cancer

Zhang

Xiao

Yang

et al. 2021

Sci Rep

Self Cite

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Because of the complex etiology, the treatment of gastric cancer is a formidable challenge for contemporary medical. The current treatment method focuses on traditional surgical procedures, supplemented by other treatments. Among these other treatments, Traditional Chinese Medicine (TCM) plays an important role. Here, we used the systems pharmacology approach to reveal the potential molecular mechanism of PRGRC on gastric cancer which composes of Pinellia ternata(Thunb.) Breit., Rheum palmatumL., Gentiana scabraBunge, Radix Aucklandiae and Citrus aurantium L. This approach combines pharmacokinetics analysis with pharmacodynamics evaluation for the active compounds screening, targets prediction and pathways assessing. Firstly, through pharmacokinetic evaluation and target prediction models, 83 potential compounds and 184 gastric cancer-related targets were screened out. Then, the results of network analysis suggested that the targets of PRGRC were mainly involved two aspects: apoptosis and inflammation. Finally, we verified the reliability of the above analysis at the cellular level by using naringenin and luteolin with good pharmacokinetic activity as representative compounds. Overall, we found that PRGRC could influence the development of gastric cancer from a multi-scale perspective. This study provided a new direction for analyzing the mechanism of TCM.

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Systems pharmacology unravels the synergic target space and therapeutic potential of Rhodiola rosea L. for non-small cell lung cancer

Cited by 15 publications

References 72 publications

WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

The Traditional Mongolian Medicine Qiqirigan-8 Effects on Lipid Metabolism and Inflammation in Obesity: Pharmacodynamic Evaluation and Relevant Metabolites

Systems pharmacology to reveal multi-scale mechanisms of traditional Chinese medicine for gastric cancer

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