Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,netwo...Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,network pharmacology was employed to analyze the mechanism of cholestatic liver damage.An adeno-associated virus overexpressing SULT1E1(rAAV8-SULT1E1)was constructed and the hepatotoxicity of SPF,psoralen,and isopsoralen was determined.Methods:By utilizing three databases inclding TCMSP,TCMID,and BATMAN-TCM,the targets of the three databases were summarized,and a total of 45 psoralen compounds were included.Network pharmacology analysis was then performed.The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo.SPF(10 g/kg),psoralen,and isopsoralen(50 mg/kg each)were intragastrically administered to mice for30 d.B-ultrasound and samples were collected and examined for follow-up experiments.Results:A total of 854 targets were predicted for 45 active components,with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF.A total of 126 pathways were enriched based on KEGG pathway analysis,with the"estrogen signaling pathway"identified as one of the top 20 pathways.In terms of pathological hepatic changes,treated mice had visually swollen hepatocytes,dilated bile ducts,and elevated serum biochemical markers,which were more prominent in mice treated with isopsoralen than in those treated with other compounds.Notably,the overexpression of SULT1E1 could reverse liver damage in each treatment group.B-ultrasound was used to observe the size of the gallbladder in vivo.The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-,psoralen-,and isopsoralen-treated groups,especially the SPF group.Compared with the expression levels in the negative control group(rAAV8-empty+con),the expression levels of FXR,Mrp2,Bsep,SULT1E1,SULT2A1,Ntcp,and Nrf2 decreased,whereas those of CYP7a1 and IL-6 increased in the SPF-,psoralen-,and isopsoralen-treated groups.Conclusion:The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators,indicating that SULT1E1 is an important target gene for SPF-induced liver damage.The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.展开更多
The theory of“Salt-processing enhancing drug into kidney meridian”was firstly put forward by Chen Jiamu,a medical doctor of Xin’an,in“Enlightening Primer of Materia Medica”.This theory integrates the theory of th...The theory of“Salt-processing enhancing drug into kidney meridian”was firstly put forward by Chen Jiamu,a medical doctor of Xin’an,in“Enlightening Primer of Materia Medica”.This theory integrates the theory of the five elements of Chinese medicine that the five flavors enter into the five viscera,and forms the theory of the role of the auxiliary materials of Chinese medicine concoctions.This theory is an important guiding significance for the clinical use of raw and cooked Chinese medicine tablets.At present,there are more studies on the theory of“Salt-processing enhancing drug into kidney meridian”in the literature,mainly focusing on the chemical composition,efficacy changes and the concoction mechanism of salt products of traditional Chinese medicines before and after salt preparation.There are relatively few review papers on the theory of“Salt-processing enhancing drug into kidney meridian”from the perspectives of auxiliary salt and attribution of meridians.In this paper,through reviewing relevant ancient books and literature,and on the basis of the previous review articles,this paper centers on the auxiliary salt,and conducts in-depth excavation and elaboration in terms of its sources,types,and the historical evolution of the salt production method.From the perspective of categorization,focusing on the core theory of“Kidney stores essence,governing reproduction,bone and generating marrow,water and brain”,we summarize the changes in efficacy before and after the salt preparation of kidney tonic traditional Chinese medicines,the changes in external and internal constituents as well as the scientific connotation of the concocting mechanism behind the effect-constituent changes.The scientific connotation of the concoction theory of“Salt-processing enhancing drug into kidney meridian”was initially elucidated,providing a new reference model for the study of the theory of Chinese medicine concoction attribution.展开更多
Salt-processed Alismatis Rhizoma(SAR)is extensively used in clinical practice and exhibits a more robust urination-promoting effect than Alismatis Rhizoma(AR).This study employed ultra-performance liquid chromatograph...Salt-processed Alismatis Rhizoma(SAR)is extensively used in clinical practice and exhibits a more robust urination-promoting effect than Alismatis Rhizoma(AR).This study employed ultra-performance liquid chromatography–quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and pattern analysis to compare the terpenoids between AR and SAR.Additionally,this study compared the effects of AR and SAR on the gene expression in the kidneys of the rat model of edema(syndrome of kidney Yin deficiency)by transcriptomics to decipher the mechanism of salt processing.Materials and methods:AR and SAR were extracted by ultrasonication,and data were collected by UPLC-Q-TOF-MS in the positive ionmode.Transcriptome sequencing was employed to determine the gene expression levels of the ratmodel treated with AR and SAR,and the differentially expressed genes(DEGs)were obtained.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment was performed for the DEGs.The protein-protein interaction(PPI)network was built,on the basis of which the core targets were screened out.Finally,real-time quantitative polymerase chain reaction(RT-PCR)was conducted to verify the core targets.Results:A total of 63 terpenoids were detected in AR and SAR,and salt processing had a significant effect on the content of terpenoids.AR and SAR mainly participated in the regulation of inflammation and immune responses,and SAR regulated more DEGs than AR.Additionally,SAR exerted more extensive regulatory effects on the targets than AR.Conclusion:Salt processing mainly changes the content of chemical compounds in AR,which may indirectly optimize the proportion of the main compounds to enhance the therapeutic effect while reducing the toxicity.AR and SAR mainly ameliorate the edema due to kidney Yin deficiency by reducing inflammation and improving immunity.Finally,SAR regulates more genes and signaling pathways and exerts more extensive regulatory effects than AR.展开更多
基金supported by the National Natural Science Foundation of China(81973484 and 82304736)the 2022 Natural Science Foundation of Nanjing University of Chinese Medicine(XZR2021085)。
文摘Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,network pharmacology was employed to analyze the mechanism of cholestatic liver damage.An adeno-associated virus overexpressing SULT1E1(rAAV8-SULT1E1)was constructed and the hepatotoxicity of SPF,psoralen,and isopsoralen was determined.Methods:By utilizing three databases inclding TCMSP,TCMID,and BATMAN-TCM,the targets of the three databases were summarized,and a total of 45 psoralen compounds were included.Network pharmacology analysis was then performed.The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo.SPF(10 g/kg),psoralen,and isopsoralen(50 mg/kg each)were intragastrically administered to mice for30 d.B-ultrasound and samples were collected and examined for follow-up experiments.Results:A total of 854 targets were predicted for 45 active components,with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF.A total of 126 pathways were enriched based on KEGG pathway analysis,with the"estrogen signaling pathway"identified as one of the top 20 pathways.In terms of pathological hepatic changes,treated mice had visually swollen hepatocytes,dilated bile ducts,and elevated serum biochemical markers,which were more prominent in mice treated with isopsoralen than in those treated with other compounds.Notably,the overexpression of SULT1E1 could reverse liver damage in each treatment group.B-ultrasound was used to observe the size of the gallbladder in vivo.The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-,psoralen-,and isopsoralen-treated groups,especially the SPF group.Compared with the expression levels in the negative control group(rAAV8-empty+con),the expression levels of FXR,Mrp2,Bsep,SULT1E1,SULT2A1,Ntcp,and Nrf2 decreased,whereas those of CYP7a1 and IL-6 increased in the SPF-,psoralen-,and isopsoralen-treated groups.Conclusion:The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators,indicating that SULT1E1 is an important target gene for SPF-induced liver damage.The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.
基金supported by The Youth Project of the National Natural Science Foundation of China(No.82204623)Key scientific research projects in universities in Anhui Province(No.2022AH050471)+1 种基金Young Science and Technology Talents Cultivation Program of Anhui University of Traditional Chinese Medicine(No.2021qnyc04)Scientific Research Team Program of Anhui Colleges and Universities(No.2022AH010036).
文摘The theory of“Salt-processing enhancing drug into kidney meridian”was firstly put forward by Chen Jiamu,a medical doctor of Xin’an,in“Enlightening Primer of Materia Medica”.This theory integrates the theory of the five elements of Chinese medicine that the five flavors enter into the five viscera,and forms the theory of the role of the auxiliary materials of Chinese medicine concoctions.This theory is an important guiding significance for the clinical use of raw and cooked Chinese medicine tablets.At present,there are more studies on the theory of“Salt-processing enhancing drug into kidney meridian”in the literature,mainly focusing on the chemical composition,efficacy changes and the concoction mechanism of salt products of traditional Chinese medicines before and after salt preparation.There are relatively few review papers on the theory of“Salt-processing enhancing drug into kidney meridian”from the perspectives of auxiliary salt and attribution of meridians.In this paper,through reviewing relevant ancient books and literature,and on the basis of the previous review articles,this paper centers on the auxiliary salt,and conducts in-depth excavation and elaboration in terms of its sources,types,and the historical evolution of the salt production method.From the perspective of categorization,focusing on the core theory of“Kidney stores essence,governing reproduction,bone and generating marrow,water and brain”,we summarize the changes in efficacy before and after the salt preparation of kidney tonic traditional Chinese medicines,the changes in external and internal constituents as well as the scientific connotation of the concocting mechanism behind the effect-constituent changes.The scientific connotation of the concoction theory of“Salt-processing enhancing drug into kidney meridian”was initially elucidated,providing a new reference model for the study of the theory of Chinese medicine concoction attribution.
基金funded by the National Natural Science Foundation of China(Grant No.82003951).
文摘Salt-processed Alismatis Rhizoma(SAR)is extensively used in clinical practice and exhibits a more robust urination-promoting effect than Alismatis Rhizoma(AR).This study employed ultra-performance liquid chromatography–quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and pattern analysis to compare the terpenoids between AR and SAR.Additionally,this study compared the effects of AR and SAR on the gene expression in the kidneys of the rat model of edema(syndrome of kidney Yin deficiency)by transcriptomics to decipher the mechanism of salt processing.Materials and methods:AR and SAR were extracted by ultrasonication,and data were collected by UPLC-Q-TOF-MS in the positive ionmode.Transcriptome sequencing was employed to determine the gene expression levels of the ratmodel treated with AR and SAR,and the differentially expressed genes(DEGs)were obtained.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment was performed for the DEGs.The protein-protein interaction(PPI)network was built,on the basis of which the core targets were screened out.Finally,real-time quantitative polymerase chain reaction(RT-PCR)was conducted to verify the core targets.Results:A total of 63 terpenoids were detected in AR and SAR,and salt processing had a significant effect on the content of terpenoids.AR and SAR mainly participated in the regulation of inflammation and immune responses,and SAR regulated more DEGs than AR.Additionally,SAR exerted more extensive regulatory effects on the targets than AR.Conclusion:Salt processing mainly changes the content of chemical compounds in AR,which may indirectly optimize the proportion of the main compounds to enhance the therapeutic effect while reducing the toxicity.AR and SAR mainly ameliorate the edema due to kidney Yin deficiency by reducing inflammation and improving immunity.Finally,SAR regulates more genes and signaling pathways and exerts more extensive regulatory effects than AR.
