Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treati...Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.展开更多
Background:Hohgardi-9 is a well-known traditional Mongolian drug that relieves cough and removes phlegm.Although it is widely used to treat lung diseases clinically,Hohgardi-9’s bioactive constituents and mechanism o...Background:Hohgardi-9 is a well-known traditional Mongolian drug that relieves cough and removes phlegm.Although it is widely used to treat lung diseases clinically,Hohgardi-9’s bioactive constituents and mechanism of action are unknown.In this study,we explored the bioactive compounds in Hohgardi-9 and the mechanism underlying its therapeutic effect against acute lung injury(ALI).Methods:We obtained the main components of Hohgardi-9 and analyzed the targets related to ALI by searching the traditional Chinese medicine systems pharmacology database and existing literature.Then,we constructed the compound-target network using Cytoscape 3.8.0 software to obtain the bioactive compounds in Hohgardi-9 against ALI.We used a string database to investigate the interaction between the possible protein targets of Hohgardi-9.We also performed Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict its anti-ALI mechanism.Further,to verify the therapeutical effects of Hohgardi-9,we used an ALI rat model and analyzed the components of Hohgardi-9 found in the rat plasma using ultra-high-performance liquid chromatography coupled with Q-Exactive mass spectrometry.Results:The network pharmacology and plasma component analysis showed that Hohgardi-9 contained 31 potentially bioactive components,including quercetin,herbacetin,izoteolin,and columbinetin acetate,which affected the NF-κB,TLR,and TNF signaling pathways via key targets,such as RELA(p65)and TLR4.The in vivo experiments using hematoxylin and eosin staining revealed that Hohgardi-9 significantly improved lung tissue injury and pulmonary edema in ALI rats.Simultaneously,Hohgardi-9 significantly reduced the expression levels of genes encoding inflammatory factors,such as TRL4,TNF-α,IL-1β,and ICAM1,in the lungs of ALI rats.Conclusion:Hohgardi-9 alleviated ALI by inhibiting inflammation-related gene expression through its active ingredients,such as quercetin and herbacetin.展开更多
基金supported by grants The Natural Science Foundation of Inner Mongolia(2019MS08104)The Natural Science Foundation of Inner Mongolia(2022ZD09)The Central Government Guiding Special Funds for Development of Local Science and Technology(2020ZY0020).
文摘Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.
基金supported by grants Inner Mongolia Plan of Science and Technology(Grant number:2020GG0005)The Central Government Guiding Special Funds for Development of Local Science and Technology(2020ZY0020).Peer review information。
文摘Background:Hohgardi-9 is a well-known traditional Mongolian drug that relieves cough and removes phlegm.Although it is widely used to treat lung diseases clinically,Hohgardi-9’s bioactive constituents and mechanism of action are unknown.In this study,we explored the bioactive compounds in Hohgardi-9 and the mechanism underlying its therapeutic effect against acute lung injury(ALI).Methods:We obtained the main components of Hohgardi-9 and analyzed the targets related to ALI by searching the traditional Chinese medicine systems pharmacology database and existing literature.Then,we constructed the compound-target network using Cytoscape 3.8.0 software to obtain the bioactive compounds in Hohgardi-9 against ALI.We used a string database to investigate the interaction between the possible protein targets of Hohgardi-9.We also performed Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict its anti-ALI mechanism.Further,to verify the therapeutical effects of Hohgardi-9,we used an ALI rat model and analyzed the components of Hohgardi-9 found in the rat plasma using ultra-high-performance liquid chromatography coupled with Q-Exactive mass spectrometry.Results:The network pharmacology and plasma component analysis showed that Hohgardi-9 contained 31 potentially bioactive components,including quercetin,herbacetin,izoteolin,and columbinetin acetate,which affected the NF-κB,TLR,and TNF signaling pathways via key targets,such as RELA(p65)and TLR4.The in vivo experiments using hematoxylin and eosin staining revealed that Hohgardi-9 significantly improved lung tissue injury and pulmonary edema in ALI rats.Simultaneously,Hohgardi-9 significantly reduced the expression levels of genes encoding inflammatory factors,such as TRL4,TNF-α,IL-1β,and ICAM1,in the lungs of ALI rats.Conclusion:Hohgardi-9 alleviated ALI by inhibiting inflammation-related gene expression through its active ingredients,such as quercetin and herbacetin.
