دانلود رایگان مقاله انگلیسی یک رویکرد فارماکولوژی شبکه برای کشف مکانیزم های متعدد Hedyotis diffusa Willd. در سرطان کولورکتال - هینداوی 2018

Background. As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC) remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW) has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective. The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods. This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results. The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility.Conclusions.This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

4. Conclusion

In our present study, we obtained 43 active ingredients from HDW and predicted 266 potential targets, suggesting that HDW was a complex agent that consisted of multiple components and affected numerous distinct targets. The network analysis uncovered that HDW probably exerted its pharmacological effects on CRC via modulating certain targets, including HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The GO analysis of targets disclosed that the ingredients of HDW possibly produced synergistic effects for treating CRC mainly by regulating numerous biological processes, like regulation of peptidylserine phosphorylation, ErbB2 signaling pathway, and Ras protein signal transduction. Meanwhile, the pathway analysis in our work indicated that HDW might simultaneously act on diverse signaling pathways associated with the pathogenesis of CRC, including colorectal cancer (hsa05210), pathways in cancer (hsa05200), PI3K-AKT signaling pathway (hsa04151), and MAPK signaling pathway (hsa04010).