Background:Panax notoginseng(PNE)is a prominent traditional Chinese medicine with extensive beneficial effects on the immune system.However,the precise mechanism of PNE in treating inflammatory bowel disease(IBD)remai...Background:Panax notoginseng(PNE)is a prominent traditional Chinese medicine with extensive beneficial effects on the immune system.However,the precise mechanism of PNE in treating inflammatory bowel disease(IBD)remains unclear.Methods:We first used an extensive metabolomics approach utilizing UPLC-ESI-Q TRAP-MS/MS to identify the metabolite components of PNE aqueous extract.Moreover,the mechanism of PNE in treating IBD was investigated through in silico analysis including RNA-seq analysis,Network pharmacology and Molecular docking.Then a Drosophila toxin-induced intestinal inflammation model was employed to investigate further.Results:A total of 1,543 metabolites of PNE aqueous extract were characterized using UPLC-ESI-Q TRAP-MS/MS.In silico analyses showed that 97 IBD hub targets were targeted by 21 PNE ingredients.Kyoto Encyclopedia of Genes and Genomes results indicated that PNE may play an anti-IBD role through the Mitogen-activated protein kinase(MAPK)signaling pathway and other immune-related signaling pathways.Moreover,11 top hits compounds of PNE show a good affinity binding to IBD targets.The experimental results demonstrated that PNE can effectively improve the survival rate of adult Drosophila while also inhibit the excessive proliferation and differentiation of intestinal stem cells induced by sodium dodecyl sulfate.Furthermore,PNE notably lower the epithelial cell mortality,the accumulation of reactive oxygen species and the activation of oxidative stress-associated jun-Nterminal kinase(JNK)pathway.Conclusion:Our data suggests that PNE aqueous extract has a significant protective impact on the intestinal homeostasis of Drosophila.These findings establish a basis for utilizing PNE in clinical investigations and managing IBD.展开更多
Panax ginseng C.A.Mey.is an important plant species used in traditional Chinese medicine,whose primary active ingredient is a ginsenoside.Ginsenoside biosynthesis is not only regulated by transcription factors but als...Panax ginseng C.A.Mey.is an important plant species used in traditional Chinese medicine,whose primary active ingredient is a ginsenoside.Ginsenoside biosynthesis is not only regulated by transcription factors but also controlled by a variety of structural genes.Nonetheless,the molecular mechanism underlying ginsenoside biosynthesis has always been a topic in the discussion of ginseng secondary metabolites.Squalene epoxidase(SQE)is a key enzyme in the mevalonic acid pathway,which affects the biosynthesis of secondary metabolites such as terpenoid.Using ginseng transcriptome,expression,and ginsenoside content databases,this study employed bioinformatic methods to systematically analyze the genes encoding SQE in ginseng.We first selected six PgSQE candidates that were closely involved in ginsenoside biosynthesis and then identified PgSQE08-01 to be highly associated with ginsenoside biosynthesis.Next,we constructed the overexpression vector pCAMBIA3301-PgSQE08-01 and the RNAi vector pART27-PgSQE08-01 and transformed ginseng adventitious roots using Agrobacterium rhizogenes,to obtain positive hairy-root clones.Thereafter,quantitative reverse transcriptionpolymerase chain reaction and high-performance liquid chromatography were used to determine the expression of relevant genes and ginsenoside content,respectively.Then,we focused on the function of PgSQE08-01 gene,which was noted to be involved in ginsenoside biosynthesis.Thus,these findings not only provided a molecular basis for the identification of important functional genes in ginseng but also enriched genetic resources for the biosynthesis of ginsenosides using synthetic biology.展开更多
Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequenc...Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng saponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also characterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the transcriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.展开更多
Objective:Based on network pharmacology and molecular docking technology to explore the mechanism of Professor Cao Enze's application of Panax notoginseng in the treatment of membranous nephropathy.Methods:TCMSP d...Objective:Based on network pharmacology and molecular docking technology to explore the mechanism of Professor Cao Enze's application of Panax notoginseng in the treatment of membranous nephropathy.Methods:TCMSP database was used to obtain the effective components and corresponding target information of Panax notoginseng,and Gene Cards database was used to obtain the disease target genes of membranous nephropathy.The intersection targets of the two were taken and the Venn diagram was drawn.The STRING database was used to obtain the protein interaction relationship,and the PPI network diagram was constructed by Cytoscape 3.9.1 software to screen out the core targets of Panax notoginseng in the treatment of membranous nephropathy.GO function and KEGG pathway enrichment analysis were performed using the David database to obtain the potential pathway of Panax notoginseng in the treatment of membranous nephropathy.Finally,Autodock software was used to verify the molecular docking of the main active components of the drug with the core targets.Results:A total of 7 effective components such as quercetin,ginsenoside rh2,Mandenol and Stigmasterol were retrieved,and 127 potential targets of Panax notoginseng in the treatment of membranous nephropathy were screened out.By PPI network topology analysis,23 core targets such as JUN,TP53,RELA,AKT1 and MAPK1 were screened out.GO functional enrichment analysis contained 703 biological processes,55 cell components and 121 molecular functions,and KEGG signal pathway enrichment analysis enriched 171 signal pathways.The results of molecular docking showed that there was a strong binding ability between the main core targets and the main components of Panax notoginseng.Conclusion:Through network pharmacology,it is concluded that Panax notoginseng treats membranous nephropathy through multiple targets and multiple pathways,which provides a theoretical basis for subsequent basic research.展开更多
产铁载体细菌通过与病原菌竞争铁元素而具有良好的生防效果。本研究从人参根组织及根际土壤中分离细菌,对其抑菌作用和产铁载体能力进行筛选,并对所筛选的1株菌株进行发酵条件的单因素和响应面优化。结果表明,共分离得到细菌菌株207株,...产铁载体细菌通过与病原菌竞争铁元素而具有良好的生防效果。本研究从人参根组织及根际土壤中分离细菌,对其抑菌作用和产铁载体能力进行筛选,并对所筛选的1株菌株进行发酵条件的单因素和响应面优化。结果表明,共分离得到细菌菌株207株,其中8株菌株既具有产铁载体的能力又对人参黑斑、根腐和锈腐病菌具有良好抑制作用;经筛选发现菌株GR-39在限铁、富铁培养基上对黑斑病菌抑菌作用差异显著,并鉴定该菌株为普城沙雷氏菌Serratiaplymuthica。通过单因素试验确定菌株GR-39在蔗糖、蛋白胨5 g/L、温度34℃、p H 8时产铁载体相对含量为74.6%;通过响应面法建立了铁载体量与自变量的回归模型,得出最佳发酵条件为蔗糖6 g/L、蛋白胨5 g/L、p H 8时铁载体产量最大达77.13%。研究表明,菌株GR-39具有较强产铁载体能力并且对人参黑斑病菌防效显著,可为多功能微生物菌剂研制提供良好菌种资源。展开更多
基金supported by the National Natural Science Foundation of China(31900366)atural Science Foundation of Liaoning Province(2023-MSLH-295)+2 种基金atural Science Foundation Initiation fund of Shenyang Medical College(20201001)Liaoning University Student Innovation and Entrepreneurship Research Fund Orders(20229033)sponsored by the Key Laboratory of Research on Pathogenesis of Allergen provoked Allergic Disease,Liaoning Province(2018-30).
文摘Background:Panax notoginseng(PNE)is a prominent traditional Chinese medicine with extensive beneficial effects on the immune system.However,the precise mechanism of PNE in treating inflammatory bowel disease(IBD)remains unclear.Methods:We first used an extensive metabolomics approach utilizing UPLC-ESI-Q TRAP-MS/MS to identify the metabolite components of PNE aqueous extract.Moreover,the mechanism of PNE in treating IBD was investigated through in silico analysis including RNA-seq analysis,Network pharmacology and Molecular docking.Then a Drosophila toxin-induced intestinal inflammation model was employed to investigate further.Results:A total of 1,543 metabolites of PNE aqueous extract were characterized using UPLC-ESI-Q TRAP-MS/MS.In silico analyses showed that 97 IBD hub targets were targeted by 21 PNE ingredients.Kyoto Encyclopedia of Genes and Genomes results indicated that PNE may play an anti-IBD role through the Mitogen-activated protein kinase(MAPK)signaling pathway and other immune-related signaling pathways.Moreover,11 top hits compounds of PNE show a good affinity binding to IBD targets.The experimental results demonstrated that PNE can effectively improve the survival rate of adult Drosophila while also inhibit the excessive proliferation and differentiation of intestinal stem cells induced by sodium dodecyl sulfate.Furthermore,PNE notably lower the epithelial cell mortality,the accumulation of reactive oxygen species and the activation of oxidative stress-associated jun-Nterminal kinase(JNK)pathway.Conclusion:Our data suggests that PNE aqueous extract has a significant protective impact on the intestinal homeostasis of Drosophila.These findings establish a basis for utilizing PNE in clinical investigations and managing IBD.
基金This work was supported by an award from the Department of Science and Technology of Jilin Province(20210402043GH and 20210204063YY).
文摘Panax ginseng C.A.Mey.is an important plant species used in traditional Chinese medicine,whose primary active ingredient is a ginsenoside.Ginsenoside biosynthesis is not only regulated by transcription factors but also controlled by a variety of structural genes.Nonetheless,the molecular mechanism underlying ginsenoside biosynthesis has always been a topic in the discussion of ginseng secondary metabolites.Squalene epoxidase(SQE)is a key enzyme in the mevalonic acid pathway,which affects the biosynthesis of secondary metabolites such as terpenoid.Using ginseng transcriptome,expression,and ginsenoside content databases,this study employed bioinformatic methods to systematically analyze the genes encoding SQE in ginseng.We first selected six PgSQE candidates that were closely involved in ginsenoside biosynthesis and then identified PgSQE08-01 to be highly associated with ginsenoside biosynthesis.Next,we constructed the overexpression vector pCAMBIA3301-PgSQE08-01 and the RNAi vector pART27-PgSQE08-01 and transformed ginseng adventitious roots using Agrobacterium rhizogenes,to obtain positive hairy-root clones.Thereafter,quantitative reverse transcriptionpolymerase chain reaction and high-performance liquid chromatography were used to determine the expression of relevant genes and ginsenoside content,respectively.Then,we focused on the function of PgSQE08-01 gene,which was noted to be involved in ginsenoside biosynthesis.Thus,these findings not only provided a molecular basis for the identification of important functional genes in ginseng but also enriched genetic resources for the biosynthesis of ginsenosides using synthetic biology.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.:81973701 and 81903767)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-D-202002)the Natural Science Foundation of Zhejiang Province(Grant No.:LZ20H290002).
文摘Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng saponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also characterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the transcriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.
基金2022 Anhui Provincial Health Research Project (No.AHWJ2022b041)2021 Anhui Provincial Key Medical and Health Specialty Construction Project (No.Anhui Health Letter 2021-273)。
文摘Objective:Based on network pharmacology and molecular docking technology to explore the mechanism of Professor Cao Enze's application of Panax notoginseng in the treatment of membranous nephropathy.Methods:TCMSP database was used to obtain the effective components and corresponding target information of Panax notoginseng,and Gene Cards database was used to obtain the disease target genes of membranous nephropathy.The intersection targets of the two were taken and the Venn diagram was drawn.The STRING database was used to obtain the protein interaction relationship,and the PPI network diagram was constructed by Cytoscape 3.9.1 software to screen out the core targets of Panax notoginseng in the treatment of membranous nephropathy.GO function and KEGG pathway enrichment analysis were performed using the David database to obtain the potential pathway of Panax notoginseng in the treatment of membranous nephropathy.Finally,Autodock software was used to verify the molecular docking of the main active components of the drug with the core targets.Results:A total of 7 effective components such as quercetin,ginsenoside rh2,Mandenol and Stigmasterol were retrieved,and 127 potential targets of Panax notoginseng in the treatment of membranous nephropathy were screened out.By PPI network topology analysis,23 core targets such as JUN,TP53,RELA,AKT1 and MAPK1 were screened out.GO functional enrichment analysis contained 703 biological processes,55 cell components and 121 molecular functions,and KEGG signal pathway enrichment analysis enriched 171 signal pathways.The results of molecular docking showed that there was a strong binding ability between the main core targets and the main components of Panax notoginseng.Conclusion:Through network pharmacology,it is concluded that Panax notoginseng treats membranous nephropathy through multiple targets and multiple pathways,which provides a theoretical basis for subsequent basic research.
文摘产铁载体细菌通过与病原菌竞争铁元素而具有良好的生防效果。本研究从人参根组织及根际土壤中分离细菌,对其抑菌作用和产铁载体能力进行筛选,并对所筛选的1株菌株进行发酵条件的单因素和响应面优化。结果表明,共分离得到细菌菌株207株,其中8株菌株既具有产铁载体的能力又对人参黑斑、根腐和锈腐病菌具有良好抑制作用;经筛选发现菌株GR-39在限铁、富铁培养基上对黑斑病菌抑菌作用差异显著,并鉴定该菌株为普城沙雷氏菌Serratiaplymuthica。通过单因素试验确定菌株GR-39在蔗糖、蛋白胨5 g/L、温度34℃、p H 8时产铁载体相对含量为74.6%;通过响应面法建立了铁载体量与自变量的回归模型,得出最佳发酵条件为蔗糖6 g/L、蛋白胨5 g/L、p H 8时铁载体产量最大达77.13%。研究表明,菌株GR-39具有较强产铁载体能力并且对人参黑斑病菌防效显著,可为多功能微生物菌剂研制提供良好菌种资源。