Widely distributed in plants,ent-kaurane diterpenoids could reduce the incidence of inflammatory.The most important active ingredient of Isodon serra(Maxim.)Hara is ent-kaurane diterpenoids,which contribute to the ant...Widely distributed in plants,ent-kaurane diterpenoids could reduce the incidence of inflammatory.The most important active ingredient of Isodon serra(Maxim.)Hara is ent-kaurane diterpenoids,which contribute to the anti-inflammatory pharmacological effects of Isodon serra.However,the ingredients,the active compounds,drug targets,inflammatory targets and exact molecular mechanism of Isodon serra in treating inflammatory are still unclear.The purpose of this study was to use the method of network pharmacological analysis to find the active compounds in Isodon serra.These active compounds match the library of ent-kaurane diterpenoids compounds we established,and we find all the eligible ent-kaurane diterpenoids compounds.Isodon serra related and anti-inflammatory targets were found and then combined to get intersection,which represented potential anti-inflammatory targets of active compounds in Isodon serra.Moreover,anti-inflammatory targets and active compounds targets protein-protein interaction network were merged to get the protein-protein interaction network intersection and core genes in anti-inflammatory target protein-protein interaction network.For the anti-inflammatory targets of Isodon serra,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were executed to confirm gene functions of Isodon serra in antagonizing inflammation.Finally,TCMSP analysis identified 10 active compounds out of 48 ent-kaurane.The pathway analysis showed enrichment for different pathways like AGE-RAGE signaling pathway in diabetic complications,small cell lung cancer and human cytomegalovirus infection,which were all connected to inflammatory.On the whole,the proposed method clearly identified the ent-kaurane diterpenoids of Isodon serra and the results gave the active compounds of Isodon serra for the first time.The combining use of the qualitative analysis of traditional Chinese medicine(TCM)and network pharmacological methods could discover potential drug targets and reveal the biological process of TCM,which would open up a new approach in the study of TCM in future.展开更多
[Objectives] To study the effects of Mangiferin( MGF) on TNF-α,iNOS,ICAM-1 and its mRNA expression in the heart,brain and kidneys of spontaneously hypertensive rats( SHR),and reveal the mechanism of its anti-inflamma...[Objectives] To study the effects of Mangiferin( MGF) on TNF-α,iNOS,ICAM-1 and its mRNA expression in the heart,brain and kidneys of spontaneously hypertensive rats( SHR),and reveal the mechanism of its anti-inflammatory injury in hypertension target organs.[Methods]SHRs were randomly divided into 5 groups: the model group,the high-dose,medium-dose,low-dose MGF groups and the Benazepril group,with 8 rats in each group,WKY rats were used for the normal control group. Besides,on-invasive blood pressure( BP) instruments were used to measure systolic blood pressure in the rats' tail artery,western blot was used to analyze the expression of TNF-α,iNOS,ICAM-1 and reverse transcription-polymerase chain reaction( RT-PCR) was used to analyze the expression of TNF-α,iNOS,ICAM-1 mRNA.[Results]Compared with the normal control group,the model group's BP level was significantly increased( P <0. 01)),but the MGF had no significant lowering BP effect( P > 0. 05); compared with the normal control group,the expression of TNF-α,iNOS,ICAM-1 and its' mRNA in the model group was significantly increased( P < 0. 05 or P < 0. 01),and MGF could reduce the level of expression of these inflammatory cytokines( P < 0. 05 or P < 0. 01); between the Benazepril group and high-dose,medium-dose,low-dose MGF groups,most of the indicators had no significant difference( P > 0. 05). [Conclusions]MGF had no significant lowering BP effect,SHR showed inflammatory injury in the heart,brain and kidneys,MGF showed improvement on the inflammatory injury,and the anti-inflammation mechanism may be associated with lowering TNF-α,i NOS and ICAM-1 and its mRNA expression.展开更多
UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α–triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the t...UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α–triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the treatment of inflammatory and autoimmune diseases induced by aberrant activation of NF-κB. In this study, we established a stable expression system for recombinant UbcH5c and solved the crystal structure of UbcH5c belonging to space group P22_12_1 with one molecule in the asymmetric unit. This study provides the basis for further study of UbcH5c including the design of UbcH5c inhibitors.展开更多
基金Hebei Administration of Traditional Chinese Medicine(Grant No.2021133)the Natural Science Foundation of Hebei Province of China(Grant No.H2019206562)the Key Projects of Hebei Education Department(Grant No.ZD2017244)。
文摘Widely distributed in plants,ent-kaurane diterpenoids could reduce the incidence of inflammatory.The most important active ingredient of Isodon serra(Maxim.)Hara is ent-kaurane diterpenoids,which contribute to the anti-inflammatory pharmacological effects of Isodon serra.However,the ingredients,the active compounds,drug targets,inflammatory targets and exact molecular mechanism of Isodon serra in treating inflammatory are still unclear.The purpose of this study was to use the method of network pharmacological analysis to find the active compounds in Isodon serra.These active compounds match the library of ent-kaurane diterpenoids compounds we established,and we find all the eligible ent-kaurane diterpenoids compounds.Isodon serra related and anti-inflammatory targets were found and then combined to get intersection,which represented potential anti-inflammatory targets of active compounds in Isodon serra.Moreover,anti-inflammatory targets and active compounds targets protein-protein interaction network were merged to get the protein-protein interaction network intersection and core genes in anti-inflammatory target protein-protein interaction network.For the anti-inflammatory targets of Isodon serra,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were executed to confirm gene functions of Isodon serra in antagonizing inflammation.Finally,TCMSP analysis identified 10 active compounds out of 48 ent-kaurane.The pathway analysis showed enrichment for different pathways like AGE-RAGE signaling pathway in diabetic complications,small cell lung cancer and human cytomegalovirus infection,which were all connected to inflammatory.On the whole,the proposed method clearly identified the ent-kaurane diterpenoids of Isodon serra and the results gave the active compounds of Isodon serra for the first time.The combining use of the qualitative analysis of traditional Chinese medicine(TCM)and network pharmacological methods could discover potential drug targets and reveal the biological process of TCM,which would open up a new approach in the study of TCM in future.
基金Supported by the Guangxi Science and Technology Infrastructure Construction Project of China(09-007-06)
文摘[Objectives] To study the effects of Mangiferin( MGF) on TNF-α,iNOS,ICAM-1 and its mRNA expression in the heart,brain and kidneys of spontaneously hypertensive rats( SHR),and reveal the mechanism of its anti-inflammatory injury in hypertension target organs.[Methods]SHRs were randomly divided into 5 groups: the model group,the high-dose,medium-dose,low-dose MGF groups and the Benazepril group,with 8 rats in each group,WKY rats were used for the normal control group. Besides,on-invasive blood pressure( BP) instruments were used to measure systolic blood pressure in the rats' tail artery,western blot was used to analyze the expression of TNF-α,iNOS,ICAM-1 and reverse transcription-polymerase chain reaction( RT-PCR) was used to analyze the expression of TNF-α,iNOS,ICAM-1 mRNA.[Results]Compared with the normal control group,the model group's BP level was significantly increased( P <0. 01)),but the MGF had no significant lowering BP effect( P > 0. 05); compared with the normal control group,the expression of TNF-α,iNOS,ICAM-1 and its' mRNA in the model group was significantly increased( P < 0. 05 or P < 0. 01),and MGF could reduce the level of expression of these inflammatory cytokines( P < 0. 05 or P < 0. 01); between the Benazepril group and high-dose,medium-dose,low-dose MGF groups,most of the indicators had no significant difference( P > 0. 05). [Conclusions]MGF had no significant lowering BP effect,SHR showed inflammatory injury in the heart,brain and kidneys,MGF showed improvement on the inflammatory injury,and the anti-inflammation mechanism may be associated with lowering TNF-α,i NOS and ICAM-1 and its mRNA expression.
基金supported by the National Natural Science Foundation of China(grants 21372078,81302697 and 81230090)the National S&T Major Project of China(grant 2013ZX09507004)+1 种基金the Shanghai Committee of Science and Technology(grant 14431902400)the Fundamental Research Funds for the Central Universities
文摘UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α–triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the treatment of inflammatory and autoimmune diseases induced by aberrant activation of NF-κB. In this study, we established a stable expression system for recombinant UbcH5c and solved the crystal structure of UbcH5c belonging to space group P22_12_1 with one molecule in the asymmetric unit. This study provides the basis for further study of UbcH5c including the design of UbcH5c inhibitors.
