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 sil...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.展开更多
The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction(HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the mo...The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction(HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2 R proteins were established using the homology modelling(HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.展开更多
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)+1 种基金the Talent Fund of Anhui Science and Technology University(No.SPWD201602)Education Department of Anhui Province(No.gxfx2017076)
文摘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 Youth Fund from Anhui Science and Technology University(No.ZRC2013341)the National Science and Technology Major Project'Creation of Major New Drugs'of China(No.2012ZX09303009-002)+2 种基金China College Students Innovation and Entrepreneurship(No.2013108 79009)the National Natural Science Fundation of China(81403268)the Natural Science Foundation of the Education Bureau of Anhui Province(KJ2013z055)
文摘The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction(HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2 R proteins were established using the homology modelling(HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.
