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

Abstract

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.

Chinese herbal medicine combined with oxaliplatin-based chemotherapy for advanced gastric cancer: A systematic review and meta-analysis of contributions of specific medicinal materials to tumor response

“…The sample sizes of included trials ranged from 50 to 124. Among these included trials, one published in an English journal ( Li Y. et al, 2020 ), and other 39 trials were published in Chinese ( Chen et al, 2007 ; Chi et al, 2010 ; Hu, 2011 ; Yuan, 2011 ; Zhao, 2011 ; Zhu et al, 2011 ; Qin, 2012 ; Guo, 2014 ; Huang, 2014 ; Liu et al, 2015 ; Li et al, 2016 ; Zhao et al, 2016 ; Chu et al, 2017 ; Feng, 2017 ; Huang et al, 2017 ; Wang Y. et al, 2018 ; Yang et al, 2018 ; Yuan, 2018 ; Cai et al, 2019 ; Gu et al, 2019 ; Jiao, 2019 ; Liu et al, 2019 ; Xie, 2019 ; Yu et al, 2019 ; Zhai, 2019 ; Zhang, 2019 ; Zhong et al, 2019 ; Bao, 2020 ; Gong, 2020 ; Sun et al, 2020 ; Zhang et al, 2020 ; Zhang, 2021a ; Zhang, 2021b ; Feng et al, 2021 ; Jiang et al, 2021 ; Long, 2021 ; Zhang L. et al, 2021 ; Zhao, 2021 ; Zhong et al, 2021 ). The characteristics of included RCTs were shown in Table 1 .…”

“…RoB 2 was used to assess the quality of 40 included trials. Two trials were assessed as “High” risk of bias ( Zhao, 2011 ; Zhang, 2019 ), and 38 trials were assessed as “Some concerns” ( Chen et al, 2007 ; Chi et al, 2010 ; Hu, 2011 ; Yuan, 2011 ; Zhu et al, 2011 ; Qin, 2012 ; Guo, 2014 ; Huang, 2014 ; Liu et al, 2015 ; Li et al, 2016 ; Zhao et al, 2016 ; Chu et al, 2017 ; Feng, 2017 ; Huang et al, 2017 ; Wang Y. et al, 2018 ; Yang et al, 2018 ; Yuan, 2018 ; Cai et al, 2019 ; Gu et al, 2019 ; Jiao, 2019 ; Liu et al, 2019 ; Xie, 2019 ; Yu et al, 2019 ; Zhai, 2019 ; Zhong et al, 2019 ; Bao, 2020 ; Gong, 2020 ; Li D. H. et al, 2020 ; Sun et al, 2020 ; Zhang et al, 2020 ; Zhang, 2021a ; Zhang, 2021b ; Feng et al, 2021 ; Jiang et al, 2021 ; Long, 2021 ; Zhang L. et al, 2021 ; Zhao, 2021 ; Zhong et al, 2021 ). Most concerns were caused by the measurement of the outcomes, since the assessment of outcomes could be influenced by knowledge of interventions patients received.…”

“…With the further development of basic research, the role and mechanism of TCM in inhibiting the division and proliferation of tumor cells, promoting the apoptosis of tumor cells, inhibiting the metastasis of tumor cells, and enhancing the curative effect with chemotherapy have been gradually revealed, laying a foundation for the effective application of anti-tumor ( Zhou et al, 2016 ; Liu et al, 2020 ; Ren et al, 2020 ; Xiang et al, 2020 ; Zhang L. et al, 2021 ). Available experimental studies indicate that TCM compounds do have anti-tumor activity, but the more appropriate and accurate drug selection is still unknown.…”

Interpreting the Pharmacological Mechanisms of Sho-saiko-to on Thyroid Carcinoma through Combining Network Pharmacology and Experimental Evaluation

“…Traditional Chinese Medicine Systems Pharmacology (TCMSP), a network pharmacology online platform based on Chinese herbal medicines, contains the relationships among diseases, targets, and drugs. 39 All herbs components of Sho-saiko-to were searched in the TCMSP database, and the active molecules with drug-likeness (DL) ≥ 0.18 and oral bioavailability (OB) ≥ 30% were defined to have better pharmacological activities and preserved, 19 , 20 , 40 and then the corresponding target names of the molecules were filtered. Subsequently, the targets protein names were converted to corresponding gene names in the UniProt database 41 ( ) by filtering for “Popular organisms” as “Human”.…”

Evaluation of the Mechanism of Jiedu Huazhuo Quyu Formula in Treating Wilson’s Disease-Associated Liver Fibrosis by Network Pharmacology Analysis and Molecular Dynamics Simulation

“…Compounds in the herbs in JHQ, including Da Huang, Huanglian, Danshen, E Zhu, Jiang Huang, and Jinqiancao, were searched in the TCMSP database ( https://old.tcmsp-e.com/ ), and active compounds were mainly identified by integrated analysis of the pharmacokinetic properties of oral bioavailability (OB) ≥30% and drug likeness (DL) ≥0.18 [ 17 – 19 ]. An upset plot of compounds in the six herbs was generated by GENE DENOVO ( https://www.omicshare.com ) [ 20 ].…”