Objective:This study aims to explore the metabolic mechanism of the liver protective effect of an aqueous extract of Gei Herba(AEG)in blood deficiency(BD)mice.Methods:The BD mouse model was established by acetylphenyl...Objective:This study aims to explore the metabolic mechanism of the liver protective effect of an aqueous extract of Gei Herba(AEG)in blood deficiency(BD)mice.Methods:The BD mouse model was established by acetylphenylhydrazine and cyclophosphamide.A total of forty-eight female Kunming mice(18–22 g)were randomly assigned to six groups:a control group,a BD model group,a positive drug group(Danggui Yixue oral liquid),and three AEG treatment groups receiving a daily AEG dose of 1,2,4 g/kg for nine days.The serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and the protein expression of IL-1,IL-2,IL-3 and TNF-αwere determined by enzyme-linked immunosorbent assay.The liquid chromatography-mass spectrometry(LC-MS)based metabolomics was used to identify liver metabolites,and the MetaboAnalyst platform was used to analyze the metabolic pathways.Results:AEG reduced serum AST,increased IL-1,IL-2,IL-3 and decreased TNF-αto effectively alleviate liver damage in BD mice.Furthermore,metabolomics analysis revealed that the disordered mice liver metabolic profile was corrected after AEG treatment,five differential metabolites were upregulated,and the mechanism was mainly related to increasing the primary bile acid biosynthesis.Conclusion:AEG has a regulatory effect on abnormal liver metabolism in BD mice.展开更多
OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in vivo.METHODS:The chemical constituen...OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in vivo.METHODS:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry method.Then,HEL was found to suppress LPS-induced ALI in vivo.Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)groups.The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model.Leukocyte counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and immunofluorescence.Besides,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal contents.RESULTS:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance.Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung tissue.In addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturbance.CONCLUSIONS:In summary,our findings revealed that HEL has a protective effect on LPS-induced ALI in rats,and its mechanism may be related to inhibiting TLR4/NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.展开更多
文摘Objective:This study aims to explore the metabolic mechanism of the liver protective effect of an aqueous extract of Gei Herba(AEG)in blood deficiency(BD)mice.Methods:The BD mouse model was established by acetylphenylhydrazine and cyclophosphamide.A total of forty-eight female Kunming mice(18–22 g)were randomly assigned to six groups:a control group,a BD model group,a positive drug group(Danggui Yixue oral liquid),and three AEG treatment groups receiving a daily AEG dose of 1,2,4 g/kg for nine days.The serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and the protein expression of IL-1,IL-2,IL-3 and TNF-αwere determined by enzyme-linked immunosorbent assay.The liquid chromatography-mass spectrometry(LC-MS)based metabolomics was used to identify liver metabolites,and the MetaboAnalyst platform was used to analyze the metabolic pathways.Results:AEG reduced serum AST,increased IL-1,IL-2,IL-3 and decreased TNF-αto effectively alleviate liver damage in BD mice.Furthermore,metabolomics analysis revealed that the disordered mice liver metabolic profile was corrected after AEG treatment,five differential metabolites were upregulated,and the mechanism was mainly related to increasing the primary bile acid biosynthesis.Conclusion:AEG has a regulatory effect on abnormal liver metabolism in BD mice.
基金Natural Science Foundation Project of Chongqing Municipality:a Metabolome-based Study on the Protective Mechanism of Yemazhui(Herba Eupatorii Lindleyani)Sesquiterpene Lactones Against Acute Lung Injury(No.cstc2021jcyj-msxmX0365)Science and Technology Research Program of Chongqing Municipal Education Commission:a Cytokine Storm-based Study of the Protective Effect of Yemazhui(Herba Eupatorii Lindleyani)Extract Intervention on COVID-19 Lung Injury(No.KJZD-K202215101)。
文摘OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in vivo.METHODS:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry method.Then,HEL was found to suppress LPS-induced ALI in vivo.Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)groups.The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model.Leukocyte counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and immunofluorescence.Besides,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal contents.RESULTS:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance.Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung tissue.In addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturbance.CONCLUSIONS:In summary,our findings revealed that HEL has a protective effect on LPS-induced ALI in rats,and its mechanism may be related to inhibiting TLR4/NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.
