Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)ha...Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)have achieved good curative effects in the treatment of CRA.However,the mechanism of whether it can alleviate CRF needs further confirmation.We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription.Through the analysis and research in this paper,we obtained 76 effective compounds and 76 drug-disease intersection targets to construct a network,indicating that quercetin,luteolin,baicalein,β-sitosterol and stigmasterol were possibly the most important compounds in YSQTG.The key targets of YSQTG for CRF were mainly enriched in IL-17 and TNF pathways.816 GO entries and 113 pathways were obtained by GO and KEGG enrichment,respectively,which proved that YSQTG might have a comprehensive therapeutic effect on CRF mainly through regulating IL-17,TNF,MAPK,NF-κB and chemokines,as well as cholinergic synapse and 5-HT synapse pathways.The results of molecular docking showed thatβ-sitosterol and stigmasterol could form PI-Alkyl or Alkyl hydrophobic interactions with CXCL8 and ESR1 at residues LEU25,ARG26,PHE65,ALA69 and LEU346,ALA350,LEU391,PHE404,LEU525,VAL533,respectively.In conclusion,the therapeutic effect of YSQTG on CRF is based on the comprehensive pharmacological effect of multicomponent,multitarget,and multichannel pathways.This study provides a theoretical basis for further experimental research.展开更多
Objective: To explore the potential mechanism of Yishen Qutong Granules(YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research. Methods: The effective components and molecul...Objective: To explore the potential mechanism of Yishen Qutong Granules(YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research. Methods: The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry(HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified. Results: Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B(NF-κB) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF-κB was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF-κB, the main therapeutic target. Conclusion: YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.展开更多
基金the Capital Health Development Scientific Research Project(2020-2-4026)Clinical and Translational Medicine Research Fund Projects of Cancer Hospital of Chinese Academy of Medical Science(2019XK320072)
文摘Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)have achieved good curative effects in the treatment of CRA.However,the mechanism of whether it can alleviate CRF needs further confirmation.We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription.Through the analysis and research in this paper,we obtained 76 effective compounds and 76 drug-disease intersection targets to construct a network,indicating that quercetin,luteolin,baicalein,β-sitosterol and stigmasterol were possibly the most important compounds in YSQTG.The key targets of YSQTG for CRF were mainly enriched in IL-17 and TNF pathways.816 GO entries and 113 pathways were obtained by GO and KEGG enrichment,respectively,which proved that YSQTG might have a comprehensive therapeutic effect on CRF mainly through regulating IL-17,TNF,MAPK,NF-κB and chemokines,as well as cholinergic synapse and 5-HT synapse pathways.The results of molecular docking showed thatβ-sitosterol and stigmasterol could form PI-Alkyl or Alkyl hydrophobic interactions with CXCL8 and ESR1 at residues LEU25,ARG26,PHE65,ALA69 and LEU346,ALA350,LEU391,PHE404,LEU525,VAL533,respectively.In conclusion,the therapeutic effect of YSQTG on CRF is based on the comprehensive pharmacological effect of multicomponent,multitarget,and multichannel pathways.This study provides a theoretical basis for further experimental research.
基金Supported by the National Natural Science Foundation of China (No. 81873283)。
文摘Objective: To explore the potential mechanism of Yishen Qutong Granules(YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research. Methods: The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry(HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified. Results: Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B(NF-κB) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF-κB was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF-κB, the main therapeutic target. Conclusion: YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.
