A Novel Systems Pharmacology Method to Investigate Molecular Mechanisms of Scutellaria barbata D. Don for Non-small Cell Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) is the most ordinary type of lung cancer which leads to 1/3 of all cancer deaths. At present, cytotoxic chemotherapy, surgical resection, radiation, and photodynamic therapy are the main strategies for NSCLC treatment. However, NSCLC is relatively resistant to the above therapeutic strategies, resulting in a rather low (20%) 5-year survival rate. Therefore, there is imperative to identify or develop efficient lead compounds for the treatment of NSCLC. Here, we report that the herb Scutellaria barbata D. Don (SBD) can effectively treat NSCLC by anti-inflammatory, promoting apoptosis, cell cycle arrest, and angiogenesis. In this work, we analyze the molecular mechanism of SBD for NSCLC treatment by applying the systems pharmacology strategy. This method combines pharmacokinetics analysis with pharmacodynamics evaluation to screen out the active compounds, predict the targets and assess the networks and pathways. Results show that 33 compounds were identified with potential anti-cancer effects. Utilizing these active compounds as probes, we predicted that 145 NSCLC related targets mainly involved four aspects: apoptosis, inflammation, cell cycle, and angiogenesis. And in vitro experiments were managed to evaluate the reliability of some vital active compounds and targets. Overall, a complete overview of the integrated systems pharmacology method provides a precise probe to elucidate the molecular mechanisms of SBD for NSCLC. Moreover, baicalein from SBD effectively inhibited tumor growth in an LLC tumor-bearing mice models, demonstrating the anti-tumor effects of SBD. Our findings further provided experimental evidence for the application in the treatment of NSCLC.

Systems pharmacology dissection of Epimedium targeting tumor microenvironment to enhance cytotoxic T lymphocyte responses in lung cancer

“…To directly reflect the relationship between compounds, targets, pathways and diseases, we constructed C-T network and T-P network by Cytoscape 3.7.0 [ 75 ], which is a popular bioinformatics package for biological network visualization and data integration. In the generated network, the nodes represent compounds, targets and pathways, and the interactions between them were represented by edges.…”

Network Pharmacology‐Based Investigation of the System‐Level Molecular Mechanisms of the Hematopoietic Activity of Samul‐Tang, a Traditional Korean Herbal Formula

“…We investigated human target genes/proteins that interact with active phytochemical compounds in SMT using the Search Tool for Interactions of Chemicals (STITCH) 5 [65], Similarity Ensemble Approach (SEA) [66], Swis-sTargetPrediction [67,68], and PharmMapper [69]. Computational modeling methods, including systematic drug targeting tool (SysDt) [70] and weighted ensemble similarity (WES) algorithm [71], were also employed for target identification as descried previously [72][73][74][75][76][77][78]. Subsequently, we confirmed detailed information regarding the targets, including their scientific name, relevant gene/protein ID, and organism, and further standardized the targets using Uniprot [79].…”

“…To identify the potential therapeutic targets of SMT, we employed an in silico approach to assess the biological interactions between the active phytochemical compounds and human genes/proteins using STITCH 5 [65], SEA [66], SwissTargetPrediction [67,68], and PharmMapper [69]. Computational modeling methods such as SysDt [70] and WES algorithm [71] were also employed for target identification as descried previously [72][73][74][75][76][77][78]. Hence, a total of 230 targets were obtained for the 16 active phytochemical compounds in SMT (Supplementary Table S3).…”

Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology

“…Fortunately, systems pharmacology, as a new discipline based on the basic theories of pharmacology and systems biology pharmacology, integrating pharmacology feature mapping, multiple targeting techniques, network pharmacology, and pathway analyses, has gradually become a powerful tool to investigate the therapeutic mechanisms of TCM (Su et al, 2019;Zhou et al, 2019). For example, Liu et al found 33 compounds with potential anticancer effects from Scutellaria barbata D. Don and investigated their mechanisms in treating non-small cell lung cancer by systems pharmacology method (Liu et al, 2018). However, previous systems pharmacology studies usually consider drug-like compounds in herb databases.…”