A metabolic data-driven systems pharmacology strategy for decoding and validating the mechanism of Compound Kushen Injection against HCC

Wang, Kexin; Chen, Yupeng; Lü, Aiping; Du, Guanhua; Qin, Xuemei; Guan, Daogang; Gao, Li

doi:10.1016/j.jep.2021.114043

Cited by 15 publications

(8 citation statements)

References 52 publications

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“…Network pharmacology emphasizes multitarget regulation of signal pathways to improve drug efficacy and reduce toxic and side effects. Network pharmacology is widely used to speculate the potential mechanism in treating complex diseases in TCM ( Wang et al, 2021 ). For example, to determine the potential mechanism of the formula in TCM for treating complex diseases and infer the mechanism of “treating the same disease with different methods” and “treating different diseases with the same method,” but there are few reports on optimization research of TCM based on network pharmacology.…”

Section: Discussionmentioning

confidence: 99%

Computational Network Pharmacology–Based Strategy to Capture Key Functional Components and Decode the Mechanism of Chai-Hu-Shu-Gan-San in Treating Depression

Wang

Yupeng

et al. 2021

Front. Pharmacol.

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Traditional Chinese medicine (TCM) usually plays therapeutic roles on complex diseases in the form of formulas. However, the multicomponent and multitarget characteristics of formulas bring great challenges to the mechanism analysis and secondary development of TCM in treating complex diseases. Modern bioinformatics provides a new opportunity for the optimization of TCM formulas. In this report, a new bioinformatics analysis of a computational network pharmacology model was designed, which takes Chai-Hu-Shu-Gan-San (CHSGS) treatment of depression as the case. In this model, effective intervention space was constructed to depict the core network of the intervention effect transferred from component targets to pathogenic genes based on a novel node importance calculation method. The intervention-response proteins were selected from the effective intervention space, and the core group of functional components (CGFC) was selected based on these intervention-response proteins. Results show that the enriched pathways and GO terms of intervention-response proteins in effective intervention space could cover 95.3 and 95.7% of the common pathways and GO terms that respond to the major functional therapeutic effects. Additionally, 71 components from 1,012 components were predicted as CGFC, the targets of CGFC enriched in 174 pathways which cover the 86.19% enriched pathways of pathogenic genes. Based on the CGFC, two major mechanism chains were inferred and validated. Finally, the core components in CGFC were evaluated by in vitro experiments. These results indicate that the proposed model with good accuracy in screening the CGFC and inferring potential mechanisms in the formula of TCM, which provides reference for the optimization and mechanism analysis of the formula in TCM.

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Section: Discussionmentioning

confidence: 99%

Computational Network Pharmacology–Based Strategy to Capture Key Functional Components and Decode the Mechanism of Chai-Hu-Shu-Gan-San in Treating Depression

Wang

Yupeng

et al. 2021

Front. Pharmacol.

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“… 27 Metabolomics results indicated that the anti-tumor effect of compound Kushen injection on liver cancer might be involved in multiple metabolic pathways. 28 Other CHP injections, such as Aidi, 29 sodium cantharidinate, 30 and Brucea javanica oil emulsion, 31 injections, showed anticancer abilities. Shenqi Shiyi Wei granule, as an oral administration of CHP, was also used widely by the metastatic GC patients, but its pharmacodynamic mechanism and clinical efficacy have not been reported.…”

Section: Discussionmentioning

confidence: 99%

Effect of Fuzheng Qingdu Therapy for Metastatic Gastric Cancer is Associated With Improved Survival: A Multicenter Propensity-Matched Study

et al. 2021

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Objective To evaluate the therapeutic effect of Traditional Chinese Medicine (TCM), specifically Fuzheng Qingdu (FZQD) therapy, on the survival time of metastatic GC patients. Patients and Methods Databases of medical records of 6 hospitals showed that 432 patients with stage IV GC were enrolled from March 1, 2012 to October 31, 2020. Propensity score matching (PSM) was used to reduce the bias caused by confounding factors in the comparison between the TCM and the non-TCM users. We used a Cox multivariate regression model to compare the hazard ratio (HR) value for mortality risk, and Kaplan-Meier survival curve for the survival time of GC patients Results The same number of subjects from the non-TCM group were matched with 122 TCM-treated patients after PSM to evaluate their overall survival (OS) and progression-free survival (PFS). Median time of OS of TCM and non-TCM users were 16.53 and 9.10 months, respectively. TCM and non-TCM groups demonstrated a 1-year survival rate of 68.5% and 34.5%, 2-year survival rate of 28.6% and 3.5%, and 3-year survival rate of 17.8% and 0.0%, respectively. A statistical difference exists in OS between the 2 groups (χ2 = 33.39 and P < .0001). The PFS of TCM users was also longer than that of non-TCM users (χ2 = 4.95 and P = 0.026). Notably, Chinese herbal decoction, Shenmai and compound Kushen injections were commonly used for FZQD therapy. Conclusion This propensity-matched study showed that FZQD therapy could improve the survival of metastatic GC patients.

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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%

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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A metabolic data-driven systems pharmacology strategy for decoding and validating the mechanism of Compound Kushen Injection against HCC

Cited by 15 publications

References 52 publications

Computational Network Pharmacology–Based Strategy to Capture Key Functional Components and Decode the Mechanism of Chai-Hu-Shu-Gan-San in Treating Depression

Computational Network Pharmacology–Based Strategy to Capture Key Functional Components and Decode the Mechanism of Chai-Hu-Shu-Gan-San in Treating Depression

Effect of Fuzheng Qingdu Therapy for Metastatic Gastric Cancer is Associated With Improved Survival: A Multicenter Propensity-Matched Study

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

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