OBJECTIVE:To evaluate the effect on influenza virus of Jinchai,a capsule made of Traditional Chinese Medicine.METHODS:Madin-darby canine kidney(MDCK) cells were infected with the FM1 strain of influenza virus A(subtyp...OBJECTIVE:To evaluate the effect on influenza virus of Jinchai,a capsule made of Traditional Chinese Medicine.METHODS:Madin-darby canine kidney(MDCK) cells were infected with the FM1 strain of influenza virus A(subtype H1N1) in vitro.They were used to explore how Jinchai affected cell adsorption,cell membrane fusion,transcription and replication of the influenza virus.Hemagglutinin(HA) protein,intracellular pH,and influenza virus protein acid(PA) polymerase subunit were detected with confocal microscopy and real-time fluorescent quantitative polymerase chain reaction.RESULTS:Jinchai significantly reduced the expression of HA and PA polymerase subunit mRNA in infected MDCK cells.Jinchai also significantly decreased intracellular pH in infected cells.CONCLUSIONS:Jinchai had strong anti-influenza activity against the influenza virus.It weakened the ability of the influenza virus to adsorb to cell wall and fuse with cell membranes in the early infection stage,and inhibited the transcription and replication of the virus.展开更多
[Objectives] To observe the pharmaceutical effect of Zijin Huadu suppository on treatment of cervicitis induced by virus,bacteria and phenol in vivo and in vitro,and provide experimental basis for evaluating its thera...[Objectives] To observe the pharmaceutical effect of Zijin Huadu suppository on treatment of cervicitis induced by virus,bacteria and phenol in vivo and in vitro,and provide experimental basis for evaluating its therapeutic effects for cervicitis. [Methods]Real-time RT-PCR and CPE methods were used to observe the inhibition of Zijin Huadu suppository on virus,and turbidimetry was used to observe bacteriostatic action; HE pathological section was used to observe cervicitis of rat,and enzyme-linked immunosorbent assay was used to detect virus' s expression in cervical tissue.[Results]In cervicitis rat model infected by HPV16,Zijin Huadu suppositories at the doses of 1. 2,0. 6 and0. 3 g/( kg·d) had significant inhibitory effect on HPV16 expression in cervical tissues,and the doses of 1. 2 and 0. 6 g/( kg·d) had significantly inhibitory effect on pathological changes of cervical tissues. In cervicities rat models infected mixedly by Escherichia coli,Neisseria gonorrhoeae and Staphylococcus aureus,Zijin Huadu suppositories at the doses of 1. 2 and 0. 6 g/( kg·d) had significant inhibitory effect on pathological changes of cervical tissues. In cervicitis rat models induced by chemical substances,Zijin Huadu suppositories at the dose of1. 2 g/( kg·d) had significant inhibitory effect on vagina and cervix lesions in rats. In vitro,Zijin Huadu suppository showed obvious inhibitory effects on HSV-2,HPV16,Staphylococcus aureus,Staphylococcus albus,Staphylococcus epidermidis,group B Streptococcus,E. coli,Pseudomonas aeruginosa,Proteusbacillus vulgaris,Neisseria gonorrhoeae and Candida albicans.[Conclusions] Zijin Huadu suppository has obvious inhibitory effect in vitro on viruses and bacteria,and could obviously improve the phenol-induced cervicitis.展开更多
[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic ...[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic stress model:except for the normal group,the rats in other groups were given corresponding chronic stress,and administered by gavage 1 h before modeling,for a total of 21 d.The changes of each indicator before and after the experiment were observed through the body weight change,the sugar water test,and open field test.The relevant hormone levels were detected by radioimmunoassay.Mouse tail suspension depression model:after continuous administration for 7 d,the activity times was recorded with the mouse automatic recorder,and the mouse immobility time was recorded after tail suspension,to explore the effects of each administration group on the tail suspension immobility time of mice.[Results]Chronic stress depression model:21 d after modeling,compared with the normal group,rats in the model group exhibited significantly reduced body weight,sucrose preference index,and horizontal and vertical movement scores(P<0.05).Compared with the model group,the low-dose Shenwei Ningyu Tablets group had significant differences in the sugar water test,horizontal and vertical movement scores(P<0.05).In addition,all three dose groups of Shenwei Ningyu Tablets could effectively reduce the content of CRF in chronic stress model rats,and the low dose group could significantly reduce the ACTH level in model rats(P<0.05).Mouse tail suspension depression model:the immobility time after tail suspension in each administration group was significantly different from that in the model group(P<0.05).[Conclusions]Shenwei Ningyu Tablets has a certain anti-depression effect on both the rat chronic stress depression model and the mouse tail suspension depression model.展开更多
At the beginning of the 20th century, Western music gradually integrated into Chinese music education institutions and various music social activities. The timbre, range and comprehensive expression of Western musical...At the beginning of the 20th century, Western music gradually integrated into Chinese music education institutions and various music social activities. The timbre, range and comprehensive expression of Western musical instruments have played an important role in promoting the performance of Chinese national musical instruments. At the same time, Chinese traditional music culture has also had an important impact on the localization of Western music in China, especially for the piano music.展开更多
Purpose:In the present study,we focused on the 46 microRNAs and 719 genes in the microRNA-gene network,reported by us,and aimed to build a research blueprint of feedforward loops and reveal the key TFs in H1N1-infecte...Purpose:In the present study,we focused on the 46 microRNAs and 719 genes in the microRNA-gene network,reported by us,and aimed to build a research blueprint of feedforward loops and reveal the key TFs in H1N1-infected mouse lung.Method:Based on microRNAs and genes in the microRNA-gene network previously reported by us,we used Jemboss software to find relationships between TFs and microRNAs(or genes),and then built a TF-microRNA-gene network exploiting the interactions between TFs and microRNAs(or genes).Next,we searched the sequences of above genes or microRNAs near the transcription start site(TSS)area,and then used the MatchTM algorithm to predict relevant TFs,and built the TF-Gene-Network.Result:We built a TF-microRNAgene network and exploreed eight key TFs,namely NF-AT1,GKLF,SRY,SOX10,AML1,MZF1,CRX and myogenin,in the network,and then constructed subgraphs of these eight TFs.Simultaneously,we predicted the possible target genes of microRNAs and identified the feedforward regulation relationship of possible TFs,microRNAs and mRNAs.The results showed that all eight factors with a score greater than 100 were TFs,namely NF-AT1,GKLF,SRY,SOX10,AML1,CRX,myogenin and MZF1.We then constructed subtables of the above eight TFs.Conclusion:In this study,TFs including NF-AT1,GKLF,SRY,SOX10,AML1,MZF1,CRX and myogenin showed the highest score(>100)not only in the TF-microRNA-gene network but also in feedforward loops,indicating that these eight TFs play the most important roles in mouse H1N1 influenza virus infection biology.展开更多
Objective:This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction(XFBD)in a mouse model of dampness-heat toxin pneumonia.By exploring how XFBD exerts its effects,we ...Objective:This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction(XFBD)in a mouse model of dampness-heat toxin pneumonia.By exploring how XFBD exerts its effects,we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action,thereby supporting its clinical application.Methods:Ultra-high-performance liquid chromatography and high-resolution mass spectrometry(HRMS)were employed to analyze the chemical constituents of XFBD.The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model,established through dampness-heat exposure and HCoV-229E infection.XFBD was administered orally,followed by assessments including lung index measurement,micro-CT imaging,viral load quantification,cytokine analysis,and histological evaluation via hematoxylin-eosin staining.Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects.A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway.Molecular docking and surface plasmon resonance(SPR)experiments confirmed the strong binding affinity between key XFBD components and PKA.Finally,PKA activators and inhibitors were applied in vitro to validate these mechanistic findings.Results:In vivo studies demonstrated that XFBD significantly reduced the lung index,improved the structural integrity of lung and tongue tissues,and decreased levels of proinflammatory mediators,including IL-6,IL-8,and TNF-α.Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation.The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects.Notably,Western blot,ELISA,molecular docking,and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression,thereby activating the cAMP/PKA signaling pathway in vitro.Conclusion:This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia.Its therapeutic effects are mediated,at least in part,through activation of the cAMP/PKA signaling pathway.These findings provide com-pelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.展开更多
Background:Influenza A viruses(IAVs)are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications.Isorhamnetin,an abundant natural ...Background:Influenza A viruses(IAVs)are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications.Isorhamnetin,an abundant natural flavonoid in fruits and medicinal plants,has recently been shown to have strong antioxidative,anti-inflammatory,and antiviral effects.Objective:This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments.Materials and methods:In the present study,the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay,cell counting kit-8 assay,real-time polymerase chain reaction,and immunofluorescence assay in vitro.Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo.Thereafter,the related protein or gene levels of factors in the mitogen-activated protein kinase(MAPK)and nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathways were determined by Western blot and immunofluorescence staining.Results:Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells,counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3.The in vivo experiment results showed that isorhamnetin(20 and 40 mg/kg)caused a significant decrease in the pulmonary index,ameliorated pathological damage in the lung tissue,decreased viral load and NA activity,and reduced cytokines and nuclear factors.Furthermore,isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2-associated X protein(Bax)imbalance induced by PR8,suppress activation of the MAPK pathway,and upregulate the expression of Nrf2 and HO-1.Conclusions:Isorhamnetin can protect against viral pneumonia by activating theNrf2/HO-1 pathway and suppressing theMAPK pathway.This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.展开更多
Objective: The aim of this study was to investigate the underlying mechanism of Shufeng Jiedu Capsule(SFJD) for treating bacterial pneumonia(BP) in vivo based on network pharmacology and experimental verification stud...Objective: The aim of this study was to investigate the underlying mechanism of Shufeng Jiedu Capsule(SFJD) for treating bacterial pneumonia(BP) in vivo based on network pharmacology and experimental verification study.Methods: Network pharmacology was used to screen the active compounds and target genes of SFJD.Then, the multi drug resistance-Pseudomonas aeruginosa(MDR-PA) mice lethal model and MDR-PA pneumonia model were established to evaluate the therapeutic effects and underlying mechanisms of SFJD.Western blot and ELISA were used to determinate the protein expression level of the IL-17 signaling pathway and JAK/STAT signaling pathway.Results: After screening, 172 potential components of SFJD were generated, based on which we constructed an SFJD-component-target-BP interaction network. The Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment revealed that SFJD could regulate the IL-17 signaling pathway and Janus kinase/signal transducer and activator of transcription(JAK/STAT) signaling pathway.Molecular docking showed that the potential target proteins had good combinations with the main active components. SFJD significantly reduced the mortality and prolonged survival days in lethal models. The lung index and pathological changes in the lung were also significantly decreased. SFJD could significantly decrease the expression of interleukin-17A(IL-17A), TNF receptor associated factor 6(TRAF6),phospho-inhibitor of nuclear factor-kappa B(p-IκB)/inhibitor of NF-κB(IκB), phospho-NF-κB p65(pNF-κB p65), phospho-protein kinase B(p-AKT)/AKT, phospho-signal transducer and activator of transcription 3(p-STAT3)/STAT3, phospho-signal transducer and activator of transcription 1(p-STAT1)/STAT1, and the protein level of interleukin-6(IL-6), tumor necrosis factor a(TNF-a), and IL-1β.Conclusion: Combined with network pharmacology and in vivo study, it was found that SFJD exerted its therapeutic effects on BP by inhibiting the IL-17 pathway and JAK/STAT signaling pathway. This study provides new evidence for SFJD in treatment of BP.展开更多
基金This work was supported by the National Key R&D Program of China(2021YFE0200300,2021YFC1712903)the Technical System of Chinese Medicine Prevention and Treatment of Influenza of the China Academy of Chinese Medical Sciences(No.ZZ13-035-09)the 2020 Annual Graduate Students Innovation Fund,School of Integrative Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin,China(ZXYCXLX202021).
基金Supported by National Significant New Drugs Creation-research and Development of Jinchai Antivirus Capsule(No.2009zx09301-005)
文摘OBJECTIVE:To evaluate the effect on influenza virus of Jinchai,a capsule made of Traditional Chinese Medicine.METHODS:Madin-darby canine kidney(MDCK) cells were infected with the FM1 strain of influenza virus A(subtype H1N1) in vitro.They were used to explore how Jinchai affected cell adsorption,cell membrane fusion,transcription and replication of the influenza virus.Hemagglutinin(HA) protein,intracellular pH,and influenza virus protein acid(PA) polymerase subunit were detected with confocal microscopy and real-time fluorescent quantitative polymerase chain reaction.RESULTS:Jinchai significantly reduced the expression of HA and PA polymerase subunit mRNA in infected MDCK cells.Jinchai also significantly decreased intracellular pH in infected cells.CONCLUSIONS:Jinchai had strong anti-influenza activity against the influenza virus.It weakened the ability of the influenza virus to adsorb to cell wall and fuse with cell membranes in the early infection stage,and inhibited the transcription and replication of the virus.
基金Supported by Joint Topics of Key Disciplines,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences(2011ZDXK-03)
文摘[Objectives] To observe the pharmaceutical effect of Zijin Huadu suppository on treatment of cervicitis induced by virus,bacteria and phenol in vivo and in vitro,and provide experimental basis for evaluating its therapeutic effects for cervicitis. [Methods]Real-time RT-PCR and CPE methods were used to observe the inhibition of Zijin Huadu suppository on virus,and turbidimetry was used to observe bacteriostatic action; HE pathological section was used to observe cervicitis of rat,and enzyme-linked immunosorbent assay was used to detect virus' s expression in cervical tissue.[Results]In cervicitis rat model infected by HPV16,Zijin Huadu suppositories at the doses of 1. 2,0. 6 and0. 3 g/( kg·d) had significant inhibitory effect on HPV16 expression in cervical tissues,and the doses of 1. 2 and 0. 6 g/( kg·d) had significantly inhibitory effect on pathological changes of cervical tissues. In cervicities rat models infected mixedly by Escherichia coli,Neisseria gonorrhoeae and Staphylococcus aureus,Zijin Huadu suppositories at the doses of 1. 2 and 0. 6 g/( kg·d) had significant inhibitory effect on pathological changes of cervical tissues. In cervicitis rat models induced by chemical substances,Zijin Huadu suppositories at the dose of1. 2 g/( kg·d) had significant inhibitory effect on vagina and cervix lesions in rats. In vitro,Zijin Huadu suppository showed obvious inhibitory effects on HSV-2,HPV16,Staphylococcus aureus,Staphylococcus albus,Staphylococcus epidermidis,group B Streptococcus,E. coli,Pseudomonas aeruginosa,Proteusbacillus vulgaris,Neisseria gonorrhoeae and Candida albicans.[Conclusions] Zijin Huadu suppository has obvious inhibitory effect in vitro on viruses and bacteria,and could obviously improve the phenol-induced cervicitis.
基金National Major Scientific and Technological Special Project for"Significant New Drugs Development"(2019ZX09301-005).
文摘[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic stress model:except for the normal group,the rats in other groups were given corresponding chronic stress,and administered by gavage 1 h before modeling,for a total of 21 d.The changes of each indicator before and after the experiment were observed through the body weight change,the sugar water test,and open field test.The relevant hormone levels were detected by radioimmunoassay.Mouse tail suspension depression model:after continuous administration for 7 d,the activity times was recorded with the mouse automatic recorder,and the mouse immobility time was recorded after tail suspension,to explore the effects of each administration group on the tail suspension immobility time of mice.[Results]Chronic stress depression model:21 d after modeling,compared with the normal group,rats in the model group exhibited significantly reduced body weight,sucrose preference index,and horizontal and vertical movement scores(P<0.05).Compared with the model group,the low-dose Shenwei Ningyu Tablets group had significant differences in the sugar water test,horizontal and vertical movement scores(P<0.05).In addition,all three dose groups of Shenwei Ningyu Tablets could effectively reduce the content of CRF in chronic stress model rats,and the low dose group could significantly reduce the ACTH level in model rats(P<0.05).Mouse tail suspension depression model:the immobility time after tail suspension in each administration group was significantly different from that in the model group(P<0.05).[Conclusions]Shenwei Ningyu Tablets has a certain anti-depression effect on both the rat chronic stress depression model and the mouse tail suspension depression model.
文摘At the beginning of the 20th century, Western music gradually integrated into Chinese music education institutions and various music social activities. The timbre, range and comprehensive expression of Western musical instruments have played an important role in promoting the performance of Chinese national musical instruments. At the same time, Chinese traditional music culture has also had an important impact on the localization of Western music in China, especially for the piano music.
基金National Natural Science Foundation of China(No.81873072)the China Academy of Chinese Medical Sciences Foundation(No.ZZ11-093,No.ZXKT17037).
文摘Purpose:In the present study,we focused on the 46 microRNAs and 719 genes in the microRNA-gene network,reported by us,and aimed to build a research blueprint of feedforward loops and reveal the key TFs in H1N1-infected mouse lung.Method:Based on microRNAs and genes in the microRNA-gene network previously reported by us,we used Jemboss software to find relationships between TFs and microRNAs(or genes),and then built a TF-microRNA-gene network exploiting the interactions between TFs and microRNAs(or genes).Next,we searched the sequences of above genes or microRNAs near the transcription start site(TSS)area,and then used the MatchTM algorithm to predict relevant TFs,and built the TF-Gene-Network.Result:We built a TF-microRNAgene network and exploreed eight key TFs,namely NF-AT1,GKLF,SRY,SOX10,AML1,MZF1,CRX and myogenin,in the network,and then constructed subgraphs of these eight TFs.Simultaneously,we predicted the possible target genes of microRNAs and identified the feedforward regulation relationship of possible TFs,microRNAs and mRNAs.The results showed that all eight factors with a score greater than 100 were TFs,namely NF-AT1,GKLF,SRY,SOX10,AML1,CRX,myogenin and MZF1.We then constructed subtables of the above eight TFs.Conclusion:In this study,TFs including NF-AT1,GKLF,SRY,SOX10,AML1,MZF1,CRX and myogenin showed the highest score(>100)not only in the TF-microRNA-gene network but also in feedforward loops,indicating that these eight TFs play the most important roles in mouse H1N1 influenza virus infection biology.
基金funded by the National Key R&D Program of China(No.2021YFC1712903)the Science and Technology Innovation Project of the China Academy of ChineseMedical Sciences(No.C12021A04606)the National Natural Science Foundation of China(No.82141206,82151210).
文摘Objective:This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction(XFBD)in a mouse model of dampness-heat toxin pneumonia.By exploring how XFBD exerts its effects,we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action,thereby supporting its clinical application.Methods:Ultra-high-performance liquid chromatography and high-resolution mass spectrometry(HRMS)were employed to analyze the chemical constituents of XFBD.The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model,established through dampness-heat exposure and HCoV-229E infection.XFBD was administered orally,followed by assessments including lung index measurement,micro-CT imaging,viral load quantification,cytokine analysis,and histological evaluation via hematoxylin-eosin staining.Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects.A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway.Molecular docking and surface plasmon resonance(SPR)experiments confirmed the strong binding affinity between key XFBD components and PKA.Finally,PKA activators and inhibitors were applied in vitro to validate these mechanistic findings.Results:In vivo studies demonstrated that XFBD significantly reduced the lung index,improved the structural integrity of lung and tongue tissues,and decreased levels of proinflammatory mediators,including IL-6,IL-8,and TNF-α.Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation.The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects.Notably,Western blot,ELISA,molecular docking,and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression,thereby activating the cAMP/PKA signaling pathway in vitro.Conclusion:This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia.Its therapeutic effects are mediated,at least in part,through activation of the cAMP/PKA signaling pathway.These findings provide com-pelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.
基金National Natural Science Foundation of China(82104500,82141206,82305078).
文摘Background:Influenza A viruses(IAVs)are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications.Isorhamnetin,an abundant natural flavonoid in fruits and medicinal plants,has recently been shown to have strong antioxidative,anti-inflammatory,and antiviral effects.Objective:This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments.Materials and methods:In the present study,the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay,cell counting kit-8 assay,real-time polymerase chain reaction,and immunofluorescence assay in vitro.Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo.Thereafter,the related protein or gene levels of factors in the mitogen-activated protein kinase(MAPK)and nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathways were determined by Western blot and immunofluorescence staining.Results:Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells,counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3.The in vivo experiment results showed that isorhamnetin(20 and 40 mg/kg)caused a significant decrease in the pulmonary index,ameliorated pathological damage in the lung tissue,decreased viral load and NA activity,and reduced cytokines and nuclear factors.Furthermore,isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2-associated X protein(Bax)imbalance induced by PR8,suppress activation of the MAPK pathway,and upregulate the expression of Nrf2 and HO-1.Conclusions:Isorhamnetin can protect against viral pneumonia by activating theNrf2/HO-1 pathway and suppressing theMAPK pathway.This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.
基金supported by the National Natural Science Foundation of China (No. 82104500)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (No. CI2021B015)+1 种基金National Natural Science Foundation of China (No. 82141206)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (No. CI2021A04620)。
文摘Objective: The aim of this study was to investigate the underlying mechanism of Shufeng Jiedu Capsule(SFJD) for treating bacterial pneumonia(BP) in vivo based on network pharmacology and experimental verification study.Methods: Network pharmacology was used to screen the active compounds and target genes of SFJD.Then, the multi drug resistance-Pseudomonas aeruginosa(MDR-PA) mice lethal model and MDR-PA pneumonia model were established to evaluate the therapeutic effects and underlying mechanisms of SFJD.Western blot and ELISA were used to determinate the protein expression level of the IL-17 signaling pathway and JAK/STAT signaling pathway.Results: After screening, 172 potential components of SFJD were generated, based on which we constructed an SFJD-component-target-BP interaction network. The Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment revealed that SFJD could regulate the IL-17 signaling pathway and Janus kinase/signal transducer and activator of transcription(JAK/STAT) signaling pathway.Molecular docking showed that the potential target proteins had good combinations with the main active components. SFJD significantly reduced the mortality and prolonged survival days in lethal models. The lung index and pathological changes in the lung were also significantly decreased. SFJD could significantly decrease the expression of interleukin-17A(IL-17A), TNF receptor associated factor 6(TRAF6),phospho-inhibitor of nuclear factor-kappa B(p-IκB)/inhibitor of NF-κB(IκB), phospho-NF-κB p65(pNF-κB p65), phospho-protein kinase B(p-AKT)/AKT, phospho-signal transducer and activator of transcription 3(p-STAT3)/STAT3, phospho-signal transducer and activator of transcription 1(p-STAT1)/STAT1, and the protein level of interleukin-6(IL-6), tumor necrosis factor a(TNF-a), and IL-1β.Conclusion: Combined with network pharmacology and in vivo study, it was found that SFJD exerted its therapeutic effects on BP by inhibiting the IL-17 pathway and JAK/STAT signaling pathway. This study provides new evidence for SFJD in treatment of BP.
