摘要
Objective： To elucidate the action mechanism of Xingnaojing Injection （醒脑静注射液, XNJI） for sepsis, and to target screen the potential bioactive ingredients. Methods： An integrated protocol that combines in silico target screen （molecular docking） and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target （C-T） interaction network. The XNJI＇s bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-1ipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction. Results： Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment. Conclusions： The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.
Objective： To elucidate the action mechanism of Xingnaojing Injection （醒脑静注射液, XNJI） for sepsis, and to target screen the potential bioactive ingredients. Methods： An integrated protocol that combines in silico target screen （molecular docking） and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target （C-T） interaction network. The XNJI＇s bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-1ipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction. Results： Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment. Conclusions： The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.
基金
Supported by the National Natural Science Foundation of China(No.81403268 and No.81403114)
the Public Welfare Technology Application Research Linkage Project of Anhui Province(No.1704f0704062)
the Talent Fund of Anhui Science and Technology University(No.SPWD201602)
Education Department of Anhui Province(No.gxfx2017076)
