OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in ...OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in the treatment of LPS-induced lung inflammation.METHODS:The pneumonia model was established by intraperitoneal injection of 5 mg/kg LPS in mice.Cytokines were detected by enzyme-linked immuneosorbent assay(ELISA),macrophages in lung tissue were determined by immunofluorescence,and pathwayrelated data were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot.RESULTS:The liver,thymus,and spleen index values and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)obviously increased in LPS-treated mice.FZXF decreased the white blood cell count and reduced the increase in the lung wet weight/dry weight ratio caused by LPS.The hematoxylin-eosin staining result showed that FZXF could maintain the integrity of lung tissue structure,alleviate interstitial oedema and alveolar wall thickening,and reduce inflammatory cell infiltration.Moreover,FZXF markedly reduced the expression of proinflammatory cytokines.FZXF also significantly reduced LPS-induced malondialdehyde production and increased superoxide dismutase level in the lung.By immunofluorescence,we found that FZXF could reduce macrophage infiltration.The mRNA expression levels of cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),toll-like receptor 4(TLR4)and nuclear transcription factorκB(NF-κB)in the lung tissue of mice were decreased by treatment with FZXF.In addition,FZXF inhibited the protein expression of TLR4,p-p65 and COX-2.These results indicated that FZXF could inhibit the inflammatory response of LPS induced cytokine storm in mice through TLR4/NF-κB and COX-2/PGE2 signaling pathway.CONCLUSION:These findings were suggested that FZXF prescription suppresses inflammation in LPSinduced pneumonia in mice via TLR4/NF-κB and COX-2/PGE2 pathway.展开更多
Objective:To evaluate the efficacy and safety of XuanFei TongFu method in the treatment of sepsis.Methods:The relevant literatures on the treatment of sepsis by Xuanfei Tongfu method,published by PubMed,Medline and th...Objective:To evaluate the efficacy and safety of XuanFei TongFu method in the treatment of sepsis.Methods:The relevant literatures on the treatment of sepsis by Xuanfei Tongfu method,published by PubMed,Medline and the Cochrane library,CNKI,WEIPU Database,WANFANG Database until December 2019 were searched by computer.Revman 5.3 was used to analyze the relevant literatures that met the inclusion and exclusion criteria,and to evaluate the influence of Xuanfei Tongfu method on gastrointestinal function,adverse reactions of gastrointestinal,28 day mortality.Results:a total of 17 randomized controlled clinical trials(RCTS)involving a total of 984 patients were included.Xuanfei Tongfu decoction combined with the control group can improve intestinal function.Xuanfei Tongfu decoction can reduce gastrointestinal adverse reactions,but there is no statistical significance,and reducing mortality of 28 days(RR=0.64,95%CI(0.42,0.99),P=0.04),reducing the APACHEⅡ[SMD=-0.90,95%CI(-1.49,-0.31),P=0.0003],reducing of Il-6[SMD=-0.36,95%CI(-0.62,-0.1),P=0.007],and improving IL-10 were all better than the control group,the difference was statistically significant.Conclusion:The method of Xuanfei Tongfu can enhance the gastrointestinal function,reduce the gastrointestinal adverse reactions,and improve the prognosis of sepsis patients.It may be achieved by regulating the body's immune inflammatory response.展开更多
Objective:To investigate the molecular mechanism of antiviral effect of Xuanfei Baidu Formula in the treatment of coronavirus disease 2019(COVID-19),and to provide reference for the twreatment of COVID-19 with traditi...Objective:To investigate the molecular mechanism of antiviral effect of Xuanfei Baidu Formula in the treatment of coronavirus disease 2019(COVID-19),and to provide reference for the twreatment of COVID-19 with traditional Chinese medicine.Methods:Traditional Chinese Medicine Systems Pharmacology(TCMSP)was employed to search the effective active component and targets of Xuanfei Baidu Formula.Databases,GeneCards etc.were employed to obtain the relevant target genes of COVID-19 and intersect with the targets of Xuanfei Baidu Formula to obtain the therapeutic targets.The therapeutic targets were uploaded to the STRING database to obtain protein interaction(PPI)information,and Cytoscape was utilized to construct drug-target-disease networks,high-confidence PPI networks for target proteins,and active-target-pathway networks.GO,gene ontology,functional analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis of potential targets of action were performed using the R package in Bioconductor.The main active components were molecular docking technology with 3C-like protease(3CLPro)and angiotensin-cinverting enzyme2(ACE2)and key targets of SARS-CoV-2,respectively.Results:A total of 99 effective active ingredients of Xuanfei Baidu Formula were selected,of which 22 active ingredients acting on COVID-19 could act on COVID-19 through 52 potential targets.Enrichment yielded 1,364 biological process entries and 22 KEGG pathways in GO,involving paths such as IL-17,JAK-STAT,MAPK,NF-κB,PI3K-Akt,Th1 and Th2 cell differentiation,Th17 cell differentiation,T cell receptor,vascular endothelial growth factor(VEGF)and Salmonella infection.Molecular docking technology results revealed that active components such as luteolin,beta-sitostero,formononetin,and shinpterocarpin in Xuanfei Baidu Formula embraced satisfactory binding to 3CLPro and ACE2,and also had good binding to core targets.Conclusion:Xuanfei Baidu Formula inhibits viral invasion and viral replication mainly by binding to ACE2 and 3CLPro receptors of SARS-CoV-2 through flavonoids and phytosterols,and may play a role in the treatment of COVID-19 by regulating key targets such as IL6,MAPK3,MAPK1,IL1β,CCL2,EGFR,and NOS2 after virus infection of cells,exerting anti-cytokine storm,anti-oxidation,and regulating the body's immunity.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
目的观察宣肺解毒汤治疗热毒炽盛证寻常型银屑病患者的临床疗效及对其肠道菌群的影响。方法选取2022年3月—2023年6月黑龙江中医药大学附属第二医院收治的寻常型银屑病患者84例,依据简单随机数字表法分为对照组和研究组,每组各42例。对...目的观察宣肺解毒汤治疗热毒炽盛证寻常型银屑病患者的临床疗效及对其肠道菌群的影响。方法选取2022年3月—2023年6月黑龙江中医药大学附属第二医院收治的寻常型银屑病患者84例,依据简单随机数字表法分为对照组和研究组,每组各42例。对照组采取常规西医治疗,研究组在对照组基础上采取宣肺解毒汤治疗。治疗4周后,观察比较两组患者临床疗效、不良反应情况,治疗前后中医证候积分[银屑病面积与严重程度指数(Psoriasis area and severity index,PASI)]、肠道菌群(酵母菌、双歧杆菌、乳酸杆菌、大肠埃希菌、肠球菌)、P物质(Substance P,SP)及受体神经激肽/速激肽受体1(Neurokinin-1 receptor,NK1R)水平。结果治疗后研究组治疗总有效率92.86%(39/42)明显高于对照组76.19%(32/42),差异有统计学意义(P<0.05)。治疗后两组患者红斑、浸润、皮损面积、鳞屑评分及总积分均较治疗前降低,差异有统计学意义(P<0.05);且研究组红斑、浸润、皮损面积、鳞屑评分及总积分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者酵母菌、双歧杆菌、乳酸杆菌数目均较治疗前升高,大肠埃希菌、肠球菌数目均较治疗前降低,差异有统计学意义(P<0.05);且研究组酵母菌、双歧杆菌、乳酸杆菌数目均明显高于对照组,大肠埃希菌、肠球菌数目均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血SP及NK1R水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组SP及NK1R水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗期间,研究组不良反应发生率7.14%(3/42)与对照组4.76%(2/42)比较,差异无统计学意义(P>0.05)。结论采用宣肺解毒汤治疗热毒炽盛证寻常型银屑病,可有效改善患者中医证候积分,提升疾病治疗效果,可能与其调节肠道菌群及SP、NK1R水平具有关联性,且具有安全性。展开更多
基金Emergency Corona Virus Disease 2019(COVID-19)Response Project of Dongguan:Clinical Efficacy Observation and Mechanism Study of Fuzheng Xuanfei Huashi Formula in the Treatment of COVID-19 Based on the Lingnan Theory of Epidemic Diseases(No.202071715002124)National Natural Science Foundation of China:Study on the Mechanism of Lung Inflammatory Injury Induced by Gut-derived Lipopolysaccharide and Skatole in Spleen Deficiency Animals based on Pulmonary Alveolus Macrophage Heterogeneity(No.82274381)Guangdong Basic and Applied Basic Research Foundation:Development and Industrialization of Traditional Chinese Medicine Classic and Famous Prescription Compound Formulations(No.2021ZD006)。
文摘OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in the treatment of LPS-induced lung inflammation.METHODS:The pneumonia model was established by intraperitoneal injection of 5 mg/kg LPS in mice.Cytokines were detected by enzyme-linked immuneosorbent assay(ELISA),macrophages in lung tissue were determined by immunofluorescence,and pathwayrelated data were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot.RESULTS:The liver,thymus,and spleen index values and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)obviously increased in LPS-treated mice.FZXF decreased the white blood cell count and reduced the increase in the lung wet weight/dry weight ratio caused by LPS.The hematoxylin-eosin staining result showed that FZXF could maintain the integrity of lung tissue structure,alleviate interstitial oedema and alveolar wall thickening,and reduce inflammatory cell infiltration.Moreover,FZXF markedly reduced the expression of proinflammatory cytokines.FZXF also significantly reduced LPS-induced malondialdehyde production and increased superoxide dismutase level in the lung.By immunofluorescence,we found that FZXF could reduce macrophage infiltration.The mRNA expression levels of cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),toll-like receptor 4(TLR4)and nuclear transcription factorκB(NF-κB)in the lung tissue of mice were decreased by treatment with FZXF.In addition,FZXF inhibited the protein expression of TLR4,p-p65 and COX-2.These results indicated that FZXF could inhibit the inflammatory response of LPS induced cytokine storm in mice through TLR4/NF-κB and COX-2/PGE2 signaling pathway.CONCLUSION:These findings were suggested that FZXF prescription suppresses inflammation in LPSinduced pneumonia in mice via TLR4/NF-κB and COX-2/PGE2 pathway.
基金Key R&D Plan of Shaanxi Provincial Department of Science and Technology(No.2017ZDXM-SF-109)。
文摘Objective:To evaluate the efficacy and safety of XuanFei TongFu method in the treatment of sepsis.Methods:The relevant literatures on the treatment of sepsis by Xuanfei Tongfu method,published by PubMed,Medline and the Cochrane library,CNKI,WEIPU Database,WANFANG Database until December 2019 were searched by computer.Revman 5.3 was used to analyze the relevant literatures that met the inclusion and exclusion criteria,and to evaluate the influence of Xuanfei Tongfu method on gastrointestinal function,adverse reactions of gastrointestinal,28 day mortality.Results:a total of 17 randomized controlled clinical trials(RCTS)involving a total of 984 patients were included.Xuanfei Tongfu decoction combined with the control group can improve intestinal function.Xuanfei Tongfu decoction can reduce gastrointestinal adverse reactions,but there is no statistical significance,and reducing mortality of 28 days(RR=0.64,95%CI(0.42,0.99),P=0.04),reducing the APACHEⅡ[SMD=-0.90,95%CI(-1.49,-0.31),P=0.0003],reducing of Il-6[SMD=-0.36,95%CI(-0.62,-0.1),P=0.007],and improving IL-10 were all better than the control group,the difference was statistically significant.Conclusion:The method of Xuanfei Tongfu can enhance the gastrointestinal function,reduce the gastrointestinal adverse reactions,and improve the prognosis of sepsis patients.It may be achieved by regulating the body's immune inflammatory response.
基金National Natural Science Foundation of China(No.81473592)Changchun University of Traditional Chinese Medicine graduate student“JuJing Cup”academic research and innovation project(No.FK201922)
文摘Objective:To investigate the molecular mechanism of antiviral effect of Xuanfei Baidu Formula in the treatment of coronavirus disease 2019(COVID-19),and to provide reference for the twreatment of COVID-19 with traditional Chinese medicine.Methods:Traditional Chinese Medicine Systems Pharmacology(TCMSP)was employed to search the effective active component and targets of Xuanfei Baidu Formula.Databases,GeneCards etc.were employed to obtain the relevant target genes of COVID-19 and intersect with the targets of Xuanfei Baidu Formula to obtain the therapeutic targets.The therapeutic targets were uploaded to the STRING database to obtain protein interaction(PPI)information,and Cytoscape was utilized to construct drug-target-disease networks,high-confidence PPI networks for target proteins,and active-target-pathway networks.GO,gene ontology,functional analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis of potential targets of action were performed using the R package in Bioconductor.The main active components were molecular docking technology with 3C-like protease(3CLPro)and angiotensin-cinverting enzyme2(ACE2)and key targets of SARS-CoV-2,respectively.Results:A total of 99 effective active ingredients of Xuanfei Baidu Formula were selected,of which 22 active ingredients acting on COVID-19 could act on COVID-19 through 52 potential targets.Enrichment yielded 1,364 biological process entries and 22 KEGG pathways in GO,involving paths such as IL-17,JAK-STAT,MAPK,NF-κB,PI3K-Akt,Th1 and Th2 cell differentiation,Th17 cell differentiation,T cell receptor,vascular endothelial growth factor(VEGF)and Salmonella infection.Molecular docking technology results revealed that active components such as luteolin,beta-sitostero,formononetin,and shinpterocarpin in Xuanfei Baidu Formula embraced satisfactory binding to 3CLPro and ACE2,and also had good binding to core targets.Conclusion:Xuanfei Baidu Formula inhibits viral invasion and viral replication mainly by binding to ACE2 and 3CLPro receptors of SARS-CoV-2 through flavonoids and phytosterols,and may play a role in the treatment of COVID-19 by regulating key targets such as IL6,MAPK3,MAPK1,IL1β,CCL2,EGFR,and NOS2 after virus infection of cells,exerting anti-cytokine storm,anti-oxidation,and regulating the body's immunity.
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.
文摘目的观察宣肺解毒汤治疗热毒炽盛证寻常型银屑病患者的临床疗效及对其肠道菌群的影响。方法选取2022年3月—2023年6月黑龙江中医药大学附属第二医院收治的寻常型银屑病患者84例,依据简单随机数字表法分为对照组和研究组,每组各42例。对照组采取常规西医治疗,研究组在对照组基础上采取宣肺解毒汤治疗。治疗4周后,观察比较两组患者临床疗效、不良反应情况,治疗前后中医证候积分[银屑病面积与严重程度指数(Psoriasis area and severity index,PASI)]、肠道菌群(酵母菌、双歧杆菌、乳酸杆菌、大肠埃希菌、肠球菌)、P物质(Substance P,SP)及受体神经激肽/速激肽受体1(Neurokinin-1 receptor,NK1R)水平。结果治疗后研究组治疗总有效率92.86%(39/42)明显高于对照组76.19%(32/42),差异有统计学意义(P<0.05)。治疗后两组患者红斑、浸润、皮损面积、鳞屑评分及总积分均较治疗前降低,差异有统计学意义(P<0.05);且研究组红斑、浸润、皮损面积、鳞屑评分及总积分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者酵母菌、双歧杆菌、乳酸杆菌数目均较治疗前升高,大肠埃希菌、肠球菌数目均较治疗前降低,差异有统计学意义(P<0.05);且研究组酵母菌、双歧杆菌、乳酸杆菌数目均明显高于对照组,大肠埃希菌、肠球菌数目均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血SP及NK1R水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组SP及NK1R水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗期间,研究组不良反应发生率7.14%(3/42)与对照组4.76%(2/42)比较,差异无统计学意义(P>0.05)。结论采用宣肺解毒汤治疗热毒炽盛证寻常型银屑病,可有效改善患者中医证候积分,提升疾病治疗效果,可能与其调节肠道菌群及SP、NK1R水平具有关联性,且具有安全性。
