Zijian Han1,2, Luping Song3, Kele Qi2,4, Yang Ding2,5, Mingjun Wei6, Yongcun Jia2,7. 1. People's Hospital of Ningxia Hui Autonomous Region, Department of Medical Engineering, Yinchuan 750002, China. 2. The First Affiliated Hospital of Northwest University for Nationalities, Yinchuan 750002, China. 3. People's Hospital of Ningxiang, Department of Clinical Pharmacy, Changsha 410600, China. 4. People's Hospital of Ningxia Hui Autonomous Region, Department of Emergency Medicine, Yinchuan 750002, China. 5. People's Hospital of Ningxia Hui Autonomous Region, Department of Burn and Plastic Surgery, Yinchuan 750002, China. 6. South China University of Technology, Graduate School, Guangzhou, 510006, China. 7. People's Hospital of Ningxia Hui Autonomous Region, Department of Clinical Laboratory, Yinchuan 750002, China.
Abstract
BACKGROUND: Yisui Qinghuang powder (YSQHP) is an effective traditional Chinese medicinal formulation used for the treatment of myelodysplastic syndromes (MDS). However, its pharmacological mechanism of action is unclear. MATERIALS AND METHODS: In this study, the active compounds of YSQHP were screened using the traditional Chinese medicine systems pharmacology (TCMSP) and HerDing databases, and the putative target genes of YSQHP were predicted using the STITCH and DrugBank databases. Then, we further screened the correlative biotargets of YSQHP and MDS. Finally, the compound-target-disease (C-T-D) network was conducted using Cytoscape, while GO and KEGG analyses were conducted using R software. Furthermore, DDI-CPI, a web molecular docking analysis tool, was used to verify potential targets and pathways. Finally, binding site analysis was performed to identify core targets using MOE software. RESULTS: Our results identified 19 active compounds and 273 putative target genes of YSQHP. The findings of the C-T-D network revealed that Rb1, CASP3, BCL2, and MAPK3 showed the most number of interactions, whereas indirubin, tryptanthrin, G-Rg1, G-Rb1, and G-Rh2 showed the most number of potential targets. The GO analysis showed that 17 proteins were related with STPK activity, PUP ligase binding, and kinase regulator activity. The KEGG analysis showed that PI3K/AKT, apoptosis, and the p53 pathways were the main pathways involved. DDI-CPI identified the top 25 proteins related with PI3K/AKT, apoptosis, and the p53 pathways. CASP8, GSK3B, PRKCA, and VEGFR2 were identified as the correlative biotargets of DDI-CPI and PPI, and their binding sites were found to be indirubin, G-Rh2, and G-Rf. CONCLUSION: Taken together, our results revealed that YSQHP likely exerts its antitumor effects by binding to CASP8, GSK3B, PRKCA, and VEGFR2 and by regulating the apoptosis, p53, and PI3K/AKT pathways.
BACKGROUND: Yisui Qinghuang powder (YSQHP) is an effective traditional Chinese medicinal formulation used for the treatment of myelodysplastic syndromes (MDS). However, its pharmacological mechanism of action is unclear. MATERIALS AND METHODS: In this study, the active compounds of YSQHP were screened using the traditional Chinese medicine systems pharmacology (TCMSP) and HerDing databases, and the putative target genes of YSQHP were predicted using the STITCH and DrugBank databases. Then, we further screened the correlative biotargets of YSQHP and MDS. Finally, the compound-target-disease (C-T-D) network was conducted using Cytoscape, while GO and KEGG analyses were conducted using R software. Furthermore, DDI-CPI, a web molecular docking analysis tool, was used to verify potential targets and pathways. Finally, binding site analysis was performed to identify core targets using MOE software. RESULTS: Our results identified 19 active compounds and 273 putative target genes of YSQHP. The findings of the C-T-D network revealed that Rb1, CASP3, BCL2, and MAPK3 showed the most number of interactions, whereas indirubin, tryptanthrin, G-Rg1, G-Rb1, and G-Rh2 showed the most number of potential targets. The GO analysis showed that 17 proteins were related with STPK activity, PUP ligase binding, and kinase regulator activity. The KEGG analysis showed that PI3K/AKT, apoptosis, and the p53 pathways were the main pathways involved. DDI-CPI identified the top 25 proteins related with PI3K/AKT, apoptosis, and the p53 pathways. CASP8, GSK3B, PRKCA, and VEGFR2 were identified as the correlative biotargets of DDI-CPI and PPI, and their binding sites were found to be indirubin, G-Rh2, and G-Rf. CONCLUSION: Taken together, our results revealed that YSQHP likely exerts its antitumor effects by binding to CASP8, GSK3B, PRKCA, and VEGFR2 and by regulating the apoptosis, p53, and PI3K/AKT pathways.
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