[Objectives]To investigate the potential mechanisms of action of triptolide,an active component in the traditional Chinese medicine Tripterygium wilfordii Hook F,in colorectal cancer(CRC).[Methods]Public databases wer...[Objectives]To investigate the potential mechanisms of action of triptolide,an active component in the traditional Chinese medicine Tripterygium wilfordii Hook F,in colorectal cancer(CRC).[Methods]Public databases were first searched for genes and proteins known to be associated with CRC,as well as those predicted to be targets of triptolide,and then Ingenuity Pathway Analysis(IPA)was applied to identify enriched gene pathways and networks.Networks and pathways that overlapped between CRC-associated proteins and triptolide target proteins were then used to predict candidate protein targets of triptolide in CRC.[Results]The following proteins were found to be expressed in both CRC-associated networks and triptolide target networks:JUN,FOS,CASP3,BCL2,IFNG,and VEGFA.Docking studies suggested that triptolide can fit in the binding pocket of the four top candidate triptolide target proteins(CASP3,BCL2,VEGFA and IFNG).The overlapping pathways were activation of neuroinflammation signaling,glucocorticoid receptor signaling,T helper(Th)cell differentiation,Th1/Th2 activation,and colorectal cancer metastasis signaling.[Conclusions]These results show that network pharmacology can be used to generate hypotheses about how triptolide exerts therapeutic effects in CRC.Network pharmacology may be a useful method for characterizing multi-target drugs in complex diseases.展开更多
基金National Natural Science Foundation of China(U1804179)Key Scientific and Technological Project in Henan Province(202102310190)+1 种基金Henan Science and Technology Innovation Team,Investigation on Plant Resources in Dabie Mountains and the Study and Utilization of Active Components of Special Plants(2017083)Nanhu Scholars Program for Young Scholars of Xinyang Normal University(2018001).
文摘[Objectives]To investigate the potential mechanisms of action of triptolide,an active component in the traditional Chinese medicine Tripterygium wilfordii Hook F,in colorectal cancer(CRC).[Methods]Public databases were first searched for genes and proteins known to be associated with CRC,as well as those predicted to be targets of triptolide,and then Ingenuity Pathway Analysis(IPA)was applied to identify enriched gene pathways and networks.Networks and pathways that overlapped between CRC-associated proteins and triptolide target proteins were then used to predict candidate protein targets of triptolide in CRC.[Results]The following proteins were found to be expressed in both CRC-associated networks and triptolide target networks:JUN,FOS,CASP3,BCL2,IFNG,and VEGFA.Docking studies suggested that triptolide can fit in the binding pocket of the four top candidate triptolide target proteins(CASP3,BCL2,VEGFA and IFNG).The overlapping pathways were activation of neuroinflammation signaling,glucocorticoid receptor signaling,T helper(Th)cell differentiation,Th1/Th2 activation,and colorectal cancer metastasis signaling.[Conclusions]These results show that network pharmacology can be used to generate hypotheses about how triptolide exerts therapeutic effects in CRC.Network pharmacology may be a useful method for characterizing multi-target drugs in complex diseases.
