Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an...Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.展开更多
Background:Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine.Currently,the therapeutic effect of treating schizophrenia is relatively well understood.However,there are fewer studies...Background:Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine.Currently,the therapeutic effect of treating schizophrenia is relatively well understood.However,there are fewer studies examining the underlying mechanisms of its treatment.The objective of the study was to investigate the primary mechanisms of Bupleuri Radix in treating schizophrenia through network pharmacology and clinical validation.Method:Network pharmacology revealed possible molecular mechanisms,followed by clinical verification.Sixty-seven schizophrenia patients undergoing treatment at the Hunan Brain Hospital between October and November 2022 were recruited and randomly divided into the olanzapine group and the olanzapine+Bupleuri Radix group.Additionally,32 healthy people undergoing physical examinations during the same period were included as the control group.The patient’s positive and negative symptom scale scores were compared.qPCR was used to detect the mRNA expression levels of ESR1,mTOR,EIF4E,and SMAD4 in peripheral blood.Results:Through network pharmacological analysis,it was concluded in this study that Bupleuri Radix might regulate the mTOR,PI3K-Akt,and HIF-1 signaling pathways.Clinical experiments indicated that compared with before treatment,the positive and negative symptom scale scores and total scores of the two treatment groups were significantly decreased after treatment(P<0.01).In addition,the positive and negative symptom scale scores and total scores in the olanzapine+Bupleuri Radix group were significantly decreased(P<0.01)compared to the olanzapine group after treatment.Before treatment,ESR1 mRNA expression levels in peripheral blood were significantly higher in the two treatment groups than in the control group,whereas the mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly lower(P<0.01).The mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly higher after therapy than before treatment,whereas the mRNA expression levels of ESR1 in peripheral blood were significantly lower(P<0.01).After therapy,the olanzapine+Bupleuri Radix group’s mRNA expression levels of mTOR,EIF4E,and SMAD4 were significantly higher than those of the olanzapine group,whereas the mRNA expression levels of ESR1 were significantly lower(P<0.01).Conclusion:The mechanism of Bupleuri Radix’s therapeutic efficacy in schizophrenia may involve the up-regulation of mTOR,EIF4E,and SMAD4 mRNA expression and the down-regulation of ESR1 mRNA expression in peripheral blood.展开更多
Objective: To explore the mechanism of Radix Bupleuri Treatment of Breast Cancer through network pharmacology. Methods: TCMSP Database was used and related literature was collected to screen out the active constituent...Objective: To explore the mechanism of Radix Bupleuri Treatment of Breast Cancer through network pharmacology. Methods: TCMSP Database was used and related literature was collected to screen out the active constituents of Radix Bupleuri. Multiple databases were used to search the targets of the constituents and the disease. Next, a visual map of the compound-target-path network were constructed. The protein-protein interaction network was visually analyzed. Finally, the enrichment analysis of GO biological process and pathway enrichment analysis were carried out. Results: Active compounds of Radix Bupleuri related to disease targets have been obtained,and they play therapeutic roles for breast cancer through mainly regulating target proteins such as PTGS2, NOS2, AR and ESR. Meanwhile, the active compounds of Radix Bupleuri have an impact on biological processes such as steroid receptor activity and endocrine resistance, platinum resistance, breast cancer-related signaling pathways. Hence, it plays a role in the treatment of breast cancer. Conclusion: The results of this study preliminarily validate the target and mode of Radix Bupleuri in the treatment of Breast Cancer, and lay a foundation for further revealing its mechanism of action.展开更多
Objective:To investigate the main effects of Radix Bupleuri(Chinese name called Chai Hu)in the prevention and improvement of nonalcoholic fatty liver disease using network pharmacology techniques.Methods:We used theTr...Objective:To investigate the main effects of Radix Bupleuri(Chinese name called Chai Hu)in the prevention and improvement of nonalcoholic fatty liver disease using network pharmacology techniques.Methods:We used theTraditional Chinese Medicine Systematic Pharmacologydatabase to query the main active ingredients of Radix Bupleuri;used theDisGenet database,Treatment Target Database,and DrugBank Database to screen the targets of nonalcoholic fatty liver disease;used the matchingtraditional Chinese medicine-disease targets to build the traditional Chinese medicine-component-target network system using Cytoscape software;used STRING software to build the protein protein interactionsystem and visualized the data;DAVID database was used forgene ontologyfunctional enrichment study andKyoto Encyclopedia of Genes and Genomespathway study.Results:Twelve major functional components and 175 targets have been obtained for the prevention and alleviation of nonalcoholic fatty liver disease in Radix Bupleuri;network pharmacology also confirmed the maximum degree value of kaempferol,the main active component of Radix Bupleuri;geneontologyfunctional enrichment analysis obtained the top 10 entries ofbiological process,cellular component,molecular functionand Kyoto Encyclopedia of Genes and Genomespathway analysis obtained the top 30 entries of the signalling pathway.Conclusion:Radix Bupleuri may use Fluid shear stress and atherosclerosis,Cancer,Advanced glycation end-(receptor of advanced glycation,interleukin 17,Hepatitis B,Toxoplasmosis,Relaxin,andtumor necrosis factorsignalling pathway to regulate the inflammatory response of interleukin6,tumor necrosis factor,and prostaglandin endoperoxide synthase2targets and reduce extracellular matrix deposition to improve the therapeutic effect of Nonalcoholic fatty liver disease.And the active ingredient of traditional Chinese medicine Radix Bupleuri,kaempferol,may also play a significant role in this.展开更多
基金This study is funded by the National Nature Science Foundation of China(Grant Nos.:82074323,and 81673572)Key Research and Development Program of Shanxi Province(Program No.:202102130501010)+2 种基金The major science and technology project for“Significant New Drugs Creation”(Project No.:2017ZX09301047)Research Project Supported by Shanxi Scholarship Council of China(Project No.:2020019)The special fund for Science and Technology Innovation Teams of Shanxi Province(Grant No.:202204051002011).
文摘Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.
基金funded by the Key Research and Development Program of Hunan Province(No.2022SK2163)Research Project of Hunan Provincial Health Commission(No.D202319017874,202214052635)+2 种基金Chinese Medicine Science&Research Project of Hunan Province(No.2021045)Natural Science Foundation of Hunan Province,China(No.2023JJ30339,2023JJ60292)grateful for the support by the Institute of Diagnostics of TCM,Hunan University of Chinese Medicine,Changsha,China.
文摘Background:Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine.Currently,the therapeutic effect of treating schizophrenia is relatively well understood.However,there are fewer studies examining the underlying mechanisms of its treatment.The objective of the study was to investigate the primary mechanisms of Bupleuri Radix in treating schizophrenia through network pharmacology and clinical validation.Method:Network pharmacology revealed possible molecular mechanisms,followed by clinical verification.Sixty-seven schizophrenia patients undergoing treatment at the Hunan Brain Hospital between October and November 2022 were recruited and randomly divided into the olanzapine group and the olanzapine+Bupleuri Radix group.Additionally,32 healthy people undergoing physical examinations during the same period were included as the control group.The patient’s positive and negative symptom scale scores were compared.qPCR was used to detect the mRNA expression levels of ESR1,mTOR,EIF4E,and SMAD4 in peripheral blood.Results:Through network pharmacological analysis,it was concluded in this study that Bupleuri Radix might regulate the mTOR,PI3K-Akt,and HIF-1 signaling pathways.Clinical experiments indicated that compared with before treatment,the positive and negative symptom scale scores and total scores of the two treatment groups were significantly decreased after treatment(P<0.01).In addition,the positive and negative symptom scale scores and total scores in the olanzapine+Bupleuri Radix group were significantly decreased(P<0.01)compared to the olanzapine group after treatment.Before treatment,ESR1 mRNA expression levels in peripheral blood were significantly higher in the two treatment groups than in the control group,whereas the mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly lower(P<0.01).The mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly higher after therapy than before treatment,whereas the mRNA expression levels of ESR1 in peripheral blood were significantly lower(P<0.01).After therapy,the olanzapine+Bupleuri Radix group’s mRNA expression levels of mTOR,EIF4E,and SMAD4 were significantly higher than those of the olanzapine group,whereas the mRNA expression levels of ESR1 were significantly lower(P<0.01).Conclusion:The mechanism of Bupleuri Radix’s therapeutic efficacy in schizophrenia may involve the up-regulation of mTOR,EIF4E,and SMAD4 mRNA expression and the down-regulation of ESR1 mRNA expression in peripheral blood.
基金National Natural Science Foundation of China(81970494)Fundamental Research Funds for the Central Universities of Central South University(502211903)
文摘Objective: To explore the mechanism of Radix Bupleuri Treatment of Breast Cancer through network pharmacology. Methods: TCMSP Database was used and related literature was collected to screen out the active constituents of Radix Bupleuri. Multiple databases were used to search the targets of the constituents and the disease. Next, a visual map of the compound-target-path network were constructed. The protein-protein interaction network was visually analyzed. Finally, the enrichment analysis of GO biological process and pathway enrichment analysis were carried out. Results: Active compounds of Radix Bupleuri related to disease targets have been obtained,and they play therapeutic roles for breast cancer through mainly regulating target proteins such as PTGS2, NOS2, AR and ESR. Meanwhile, the active compounds of Radix Bupleuri have an impact on biological processes such as steroid receptor activity and endocrine resistance, platinum resistance, breast cancer-related signaling pathways. Hence, it plays a role in the treatment of breast cancer. Conclusion: The results of this study preliminarily validate the target and mode of Radix Bupleuri in the treatment of Breast Cancer, and lay a foundation for further revealing its mechanism of action.
文摘Objective:To investigate the main effects of Radix Bupleuri(Chinese name called Chai Hu)in the prevention and improvement of nonalcoholic fatty liver disease using network pharmacology techniques.Methods:We used theTraditional Chinese Medicine Systematic Pharmacologydatabase to query the main active ingredients of Radix Bupleuri;used theDisGenet database,Treatment Target Database,and DrugBank Database to screen the targets of nonalcoholic fatty liver disease;used the matchingtraditional Chinese medicine-disease targets to build the traditional Chinese medicine-component-target network system using Cytoscape software;used STRING software to build the protein protein interactionsystem and visualized the data;DAVID database was used forgene ontologyfunctional enrichment study andKyoto Encyclopedia of Genes and Genomespathway study.Results:Twelve major functional components and 175 targets have been obtained for the prevention and alleviation of nonalcoholic fatty liver disease in Radix Bupleuri;network pharmacology also confirmed the maximum degree value of kaempferol,the main active component of Radix Bupleuri;geneontologyfunctional enrichment analysis obtained the top 10 entries ofbiological process,cellular component,molecular functionand Kyoto Encyclopedia of Genes and Genomespathway analysis obtained the top 30 entries of the signalling pathway.Conclusion:Radix Bupleuri may use Fluid shear stress and atherosclerosis,Cancer,Advanced glycation end-(receptor of advanced glycation,interleukin 17,Hepatitis B,Toxoplasmosis,Relaxin,andtumor necrosis factorsignalling pathway to regulate the inflammatory response of interleukin6,tumor necrosis factor,and prostaglandin endoperoxide synthase2targets and reduce extracellular matrix deposition to improve the therapeutic effect of Nonalcoholic fatty liver disease.And the active ingredient of traditional Chinese medicine Radix Bupleuri,kaempferol,may also play a significant role in this.
