Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology

Zhou, Wei; Wu, Jiarui; Zhu, Yimin; Meng, Ziqi; Liu, Xinkui; Ni, Mengwei; Jia, Shanshan; Zhang, Jingyuan; Guo, Siyu

doi:10.1186/s12906-019-2787-y

Cited by 19 publications

(16 citation statements)

References 60 publications

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“…In recent years, the application of network pharmacology, RNA-Seq technology, and bioinformatics has become a good research tool for screening bioactive ingredients with anti-cancer properties and predicting target genes and related signaling pathways. The application of in vitro cells and in vivo animal models has also provided robust technical support for verifying the biological effects of CKI [16][17][18][19][20][21][22][23][24][25][26][27] .…”

Section: Discussionmentioning

confidence: 99%

“…A TCM network pharmacology approach provides a new research paradigm for translating TCM from experience-based medicine to evidence-based medicine, which will likely accelerate TCM discovery and improve drug discovery strategies 15 . A combination of network pharmacology and experimental verification has gradually become an important way to study the mechanism of action of CKI [16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

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Cell Cycle Arrest, An Important Mechanism of Action of Compound Kushen Injection, Prevents Colorectal Cancer: Network Pharmacology Analysis and Experimental Validation

Sun¹,

Li²,

Wang³

et al. 2021

Preprint

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Compound Kushen injection (CKI) is the most widely used traditional Chinese medicine preparation for the comprehensive treatment of colorectal cancer (CRC) in China, but its underlying molecular mechanisms of action are still unclear. The present study employed a network pharmacology approach, in which we constructed a “bioactive compound-target-pathway” network. Experimental RNA sequencing (RNA-Seq) analysis was performed to identify a key “bioactive compound-target-pathway” network for subsequent experimental validation. Cell cycle, proliferation, autophagy, and apoptosis assays and a model of azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis in mice were employed to detect the biological effect of CKI on CRC. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were performed to verify the selected targets and pathways. We constructed a predicted network that included 82 bioactive compounds, 34 targets, and 33 pathways and further screened an anti-CRC CKI “biological compound (hesperetin 7-O-rutinoside, genistein 7-O-rutinoside, and trifolirhizin)-target (p53 and checkpoint kinase 1 [CHEK1])” network that targeted the “cell cycle pathway”. Validation experiments showed that CKI effectively induced the cell-cycle arrest of CRC cells in vitro and suppressed the development of CRC in vivo by downregulating the expression of p53 and CHEK1. Our findings confirmed that inducing cell-cycle arrest by CKI is an important mechanism of its anti-CRC action, which provides a direct and scientific experimental basis for the clinical application of CKI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell Cycle Arrest, An Important Mechanism of Action of Compound Kushen Injection, Prevents Colorectal Cancer: Network Pharmacology Analysis and Experimental Validation

Sun¹,

Li²,

Wang³

et al. 2021

Preprint

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“…Research showed that 20-200 µg/mL Radix Sophorae Flavescentis could induce apoptosis of human gastric cancer cells by downregulating Bcl-2 and upregulating Bax [29]. In addition, a network pharmacology method predicted that CKI inhibited the growth and metastasis of gastric cancer cells by regulating vital targets and important related pathways [30]. Previous research confirmed that five compounds (sophocarpine, matrine, oxymatrine, oxysophocarpine, and xanthohumol) of Radix Sophorae Flavescentis exerted anti-prostate cancer effects by affecting cell proliferation and apoptosis [31].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Compound Kushen Injection for Treatment of Bladder Cancer Based on Bioinformatics and Network Pharmacology With Experimental Validation

Zhang¹,

Zhang

Xiong

et al. 2020

Preprint

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Background: Bladder cancer is the most common malignant neoplasm of the urinary system. CompoundKushen injection (CKI) is a Chinese medicinal preparation that has been used clinically to treat varioustypes of cancers for more than 20 years. However, the pharmacological effect of CKI on bladder cancerrequires further clarification.Methods: Network pharmacology combined with bioinformatics was used to elucidate the therapeuticmechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI is effective againstbladder cancer was further verified in vitro using the human bladder cancer cell line T24.Results: Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI.Bioinformatics data mining revealed 5500 differentially expressed genes associated with bladder cancer.Common genes of CKI and bladder cancer suggested that CKI exerts anti-bladder cancer effects byregulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated thatCKI has a therapeutic effect on bladder cancer by synergistically regulating certain biological processes,including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes andGenomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Aktsignaling pathway. Consistently, cell experiments indicated that CKI could inhibit proliferation andmigration of T24 bladder cancer cells, and induce their apoptosis. Moreover, RT-qPCR and western blotresults indicated that CKI may treat bladder cancer by downregulating gene and protein expression levels,respectively of MMP-9, JUN, EGFR, and ERK1.Conclusions: CKI can inhibit proliferation and migration, and induce apoptosis of T24 bladder cancer cellsthrough multiple biological pathways and targets. CKI also has significant effects on regulation of key genesand proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen currentunderstanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

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“…At present, the identification methods of chemical compositions of traditional Chinese medicine (TCM) mainly include thin-layer chromatography (TLC), capillary electrophoresis (CE), highperformance liquid chromatography (HPLC), gas chromatography (GC), ultraviolet (UV) spectrophotometry, etc. [19][20][21][22] However, there are many types of chemical ingredients in TCM and the content of some active ingredients is extremely low. Therefore, it is difficult to make accurate qualitative or quantitative analysis of TCM ingredients using traditional analytical methods.…”

Section: Introductionmentioning

confidence: 99%

Rapid classification and identification of chemical constituents in Epimedium koreanum Nakai by UPLC‐Q‐TOF‐MS combined with data post‐processing techniques

Xie

Yang

et al. 2020

Phytochemical Analysis

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Introduction: Epimedium koreanum Nakai (EKN), is a well-known Chinese herbal medicine for the treatment of osteoporosis, immunosuppression, tumours and cardiovascular diseases. Comprehensive component identification is essential for elucidation of its pharmacological mechanism and quality control. However, its complex chemical composition has caused certain difficulties in the analysis of this traditional Chinese medicine (TCM). Therefore, there is an urgent need to establish a method for rapid classification and identification of EKN chemical components.Objective: To establish a method for rapid classification and identification of the main components of flavonoids, organic acids and alkaloids in EKN. Methods:The samples were analysed by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and data postprocessing techniques. The UPLC system used a BEH C 18 column to separate the total extract of EKN. The mobile phase consisted of 0.1% formic acid in water and acetonitrile, and the EKN extract was analysed by gradient elution at a flow rate of 0.4 mL/min. In both the positive and negative ion modes, the fragment information was obtained and compared with those of the characteristic fragmentations and neutral losses described in the literature to quickly identify the target compounds.Results: Finally, we successfully screened out 51 chemical components, including 40 flavonoids, nine organic acids, and two alkaloids. Conclusion:The established method not only comprehensively analysed the chemical compositions of EKN, solved the difficult problems of analysis and identification of the complex chemical compositions of the TCM, but also further promoted the development of the application of chemical compositions of TCM.

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Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology

Cited by 19 publications

References 60 publications

Cell Cycle Arrest, An Important Mechanism of Action of Compound Kushen Injection, Prevents Colorectal Cancer: Network Pharmacology Analysis and Experimental Validation

Cell Cycle Arrest, An Important Mechanism of Action of Compound Kushen Injection, Prevents Colorectal Cancer: Network Pharmacology Analysis and Experimental Validation

Mechanisms of Compound Kushen Injection for Treatment of Bladder Cancer Based on Bioinformatics and Network Pharmacology With Experimental Validation

Rapid classification and identification of chemical constituents in Epimedium koreanum Nakai by UPLC‐Q‐TOF‐MS combined with data post‐processing techniques

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