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
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
Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment...Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment.Methods:Public databases were employed to identify Cedrenol,an active component of Bupleuri Radix,and its associated gene targets.Among these,the gene RORC(also known as RORγ)was selected for detailed analysis due to its high expression correlation.Expression levels of RORC across various cancers were assessed using the TCGA pan-cancer dataset.Further analyses,including differential expression,prognostic relevance,immune infiltration,single-gene,and functional enrichment analyses,were conducted using the TCGA ccRCC dataset.Additionally,potential drug sensitivities and molecular docking interactions with RORC were explored using the GSCALite and CellMiner databases.The effects of RORC on ccRCC were also validated through cellular experiments.Results:RORC exhibited elevated expression in clear cell renal carcinoma tissue in contrast to normal tissues,and lower RORC expression was related to better prognosis.Immune cell infiltration analysis suggested that RORC may influence the penetration of cells that inhibit immune responses,such as regulatory T cells,thereby affecting ccRCC progression.Furthermore,molecular docking studies revealed that several drugs,including Axitinib,Docetaxel,Methotrexate,and Temsirolimus,have a high affinity for RORC and exhibit strong molecular binding.In cellular experiment experiments confirmed that RORC knockdown led to reduced proliferation,metastasis,and ccRCC cell invasion.Conclusion:The study implies that RORC may be a potential gene target for Bupleuri Radix in the management of ccRCC.展开更多
OBJECTIVE: To analyze the essential oils from flowers, leaves, stems, roots, and fruits of Chaihu(Radix Bupleuri Chinensis).METHODS: We extracted essential oils from different parts of Chaihu(Radix Bupleuri Chinensis)...OBJECTIVE: To analyze the essential oils from flowers, leaves, stems, roots, and fruits of Chaihu(Radix Bupleuri Chinensis).METHODS: We extracted essential oils from different parts of Chaihu(Radix Bupleuri Chinensis) using a steam distillation method. The essential oils were analyzed by gas chromatography-mass spectrometry(GC-MS). Data were collected in full scan mode(m/z 60-600). Volatile components were identified based on their retention indices and by comparing their mass spectra with those in the National Institute of Standards and Technology 2005 database assisted by tandem mass spectrometry information. The relative content of each constituent wasdetermined by area normalization.RESULTS: We identified 111 components, of which12 were common to all 5 parts, 30 were found only in roots, 14 were found only in flowers, 6 were found only in leaves, 4 were found only in stems,and 17 were found only in fruits.CONCLUSION: Our results show that the stems,flowers, leaves, and fruits of Chaihu(Radix Bupleuri Chinensis)contain a high concentration of essential oils, and that the exact composition of the essential oils differs among the plant parts. To develop new medicines and make full use of the Chaihu(Radix Bupleuri Chinensis)resource, it is important to characterize the essential oils from different parts of the plant. In future research, it will be important to determine the pharmacological effects of the various components and the essential oil mixtures.展开更多
OBJECTIVE:To investigate the bioactive compounds of Chaihu(Radix Bupleuri Chinensis)(RB)on glaucomatous optic atrophy(GOA),and to study the pharmacological mechanism.METHODS:We collected information on the bioactive c...OBJECTIVE:To investigate the bioactive compounds of Chaihu(Radix Bupleuri Chinensis)(RB)on glaucomatous optic atrophy(GOA),and to study the pharmacological mechanism.METHODS:We collected information on the bioactive compounds of RB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Targets related to bioactive compounds and GOA were also obtained.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and network analyses were performed to investigate the potential mechanism of RB against GOA.Subsequently,the main bioactive compounds of RB and targets of GOA were docked by Autodock software.Moreover,a GOA model of retinal ganglion cells(RGCs)induced by cobalt chloride was established to verify the effect of RB on GOA.RESULTS:There were 17 main bioactive compounds and 46 key targets were screened as potential players in GOA.The compound-target network mainly contained 17 compounds and 46 corresponding targets,and the key targets consisted of interleukin-6(IL-6),hypoxia inducible factor-1α(HIF1A),Caspase-3,estrogen receptor alpha(ESR1),MYC proto-oncogene(MYC),and vascular endothelial growth factor A(VEGFA).Forty-nine significantly enriched GO terms,and 134 KEGG signaling pathways were identified(P<0.05),including HIF-1,tumor necrosis factor,VEGF,prolaction,and other signaling pathways.Molecular docking results showed that the main bioactive compounds of RB exhibited the strongest binding activity with IL-6.Furthermore,experimental validation showed that the RB extract inhibited the activity and promoted apoptosis of RGCs in a dose-dependent manner.The RB extract also suppressed the expression of Bax,Caspase-3,and Caspase-9 and regulated malonaldehyde,superoxide dismutase,and glutathione peroxide by inhibiting the IL-6/HIF-1αsignaling pathway.CONCLUSIONS:The present study provided insights into the mechanism of RB on GOA.RB mainly reverses GOA by inhibiting the IL-6/HIF-1αsignaling pathway.展开更多
We investigated the potential hepatoprotective effect of Radix Bupleuri(RB) by inducing acute liver injury(ALI) in an animal model using acetaminophen(APAP) after pretreatment with RB aqueous extract for three consecu...We investigated the potential hepatoprotective effect of Radix Bupleuri(RB) by inducing acute liver injury(ALI) in an animal model using acetaminophen(APAP) after pretreatment with RB aqueous extract for three consecutive days. Compared to those of the APAP group, the biochemical and histological results of the RB pretreatment group showed lower serum aspartate transaminase(AST) and alanine transaminase(ALT) levels as well as less liver damage. Pharmacokinetic study of the toxicity related marker acetaminophen-cysteine(APC) revealed a lower exposure level in rats, suggesting that RB alleviated APAP-induced liver damage by preventing glutathione(GSH) depletion. The results of cocktail approach showed significant inhibition of CYP2 E1 and CYP3 A activity. Further investigation revealed the increasing of CYP2 E1 and CYP3 A protein was significantly inhibited in pretreatment group,while no obvious effect on gene expression was found. Therefore, this study clearly demonstrates that RB exhibited significant protective action against APAP-induced acute live injury via pretreatment, and which is partly through inhibiting the increase of activity and translation of cytochrome P450 enzymes, rather than gene transcription.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
对醋柴胡多糖(polysaccharide from vinegar-baked Bupleuri Radix,VBRBP)进行分离纯化,初步分析其结构特征并探究其联合化疗药的协同抗肝癌活性。通过水提醇沉、膜分离及纤维素层析从醋柴胡中分离纯化得到醋柴胡均一多糖,采用高效凝胶...对醋柴胡多糖(polysaccharide from vinegar-baked Bupleuri Radix,VBRBP)进行分离纯化,初步分析其结构特征并探究其联合化疗药的协同抗肝癌活性。通过水提醇沉、膜分离及纤维素层析从醋柴胡中分离纯化得到醋柴胡均一多糖,采用高效凝胶渗透色谱法、PMP柱前衍生化法、傅里叶变换红外光谱、气质联用和核磁共振波谱等方法对醋柴胡均一多糖进行结构鉴定,并测定其联合不同化疗药物对HepG2和Huh7两种肝癌细胞株的增殖抑制作用。结果表明,经过分离纯化得到的醋柴胡均一多糖5-1(polysaccharide 5-1 from vinegar-baked Bupleuri Radix,VBRBP5-1)是一种中性多糖,相对分子量为30.78 kDa,由甘露糖、半乳糖醛酸、葡萄糖、半乳糖和阿拉伯糖组成,摩尔比为1.96∶2.38∶58.48∶22.85∶14.32;主链是由1-α-D-葡萄糖、1,6-α-D-葡萄糖、1,4,6-α-D-葡萄糖、1,4-α-D-葡萄糖、1,3,6-β-D-半乳糖残基构成,支链主要含有1-β-D-半乳糖、1,4-β-D-半乳糖和1-α-L-阿拉伯糖、1,3,5-α-L-阿拉伯糖、1,5-α-L-阿拉伯糖残基片段。VBRBP5-1能增强10-羟基喜树碱、甲氨蝶呤和顺铂对肝癌细胞的抑制率,显示出协同增效作用,其中对顺铂的协同增效作用在两种肝癌细胞中均优于其他抗肿瘤药物。本研究解析了VBRBP5-1的结构并探索了其协同抗肝癌活性,为醋柴胡多糖的构效关系阐释及后续深入开发和利用提供参考。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.
基金supported by Hubei Provincial Department of Science and Technology,Innovation and Development Joint Fund(No.2022CFD145)Young Talents Project of Hubei Provincial Administration of Traditional Chinese Medicine(No.ZY2023Q002).
文摘Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment.Methods:Public databases were employed to identify Cedrenol,an active component of Bupleuri Radix,and its associated gene targets.Among these,the gene RORC(also known as RORγ)was selected for detailed analysis due to its high expression correlation.Expression levels of RORC across various cancers were assessed using the TCGA pan-cancer dataset.Further analyses,including differential expression,prognostic relevance,immune infiltration,single-gene,and functional enrichment analyses,were conducted using the TCGA ccRCC dataset.Additionally,potential drug sensitivities and molecular docking interactions with RORC were explored using the GSCALite and CellMiner databases.The effects of RORC on ccRCC were also validated through cellular experiments.Results:RORC exhibited elevated expression in clear cell renal carcinoma tissue in contrast to normal tissues,and lower RORC expression was related to better prognosis.Immune cell infiltration analysis suggested that RORC may influence the penetration of cells that inhibit immune responses,such as regulatory T cells,thereby affecting ccRCC progression.Furthermore,molecular docking studies revealed that several drugs,including Axitinib,Docetaxel,Methotrexate,and Temsirolimus,have a high affinity for RORC and exhibit strong molecular binding.In cellular experiment experiments confirmed that RORC knockdown led to reduced proliferation,metastasis,and ccRCC cell invasion.Conclusion:The study implies that RORC may be a potential gene target for Bupleuri Radix in the management of ccRCC.
基金Breeding Research Project of Chinese Medical Herbs in Sichuan Province:Study on the breeding of new Chaihu variety and cultivation and the related techniques(No.2011NZ0098-12-11)China Spark Program in 2010(No.2010GA810056)
文摘OBJECTIVE: To analyze the essential oils from flowers, leaves, stems, roots, and fruits of Chaihu(Radix Bupleuri Chinensis).METHODS: We extracted essential oils from different parts of Chaihu(Radix Bupleuri Chinensis) using a steam distillation method. The essential oils were analyzed by gas chromatography-mass spectrometry(GC-MS). Data were collected in full scan mode(m/z 60-600). Volatile components were identified based on their retention indices and by comparing their mass spectra with those in the National Institute of Standards and Technology 2005 database assisted by tandem mass spectrometry information. The relative content of each constituent wasdetermined by area normalization.RESULTS: We identified 111 components, of which12 were common to all 5 parts, 30 were found only in roots, 14 were found only in flowers, 6 were found only in leaves, 4 were found only in stems,and 17 were found only in fruits.CONCLUSION: Our results show that the stems,flowers, leaves, and fruits of Chaihu(Radix Bupleuri Chinensis)contain a high concentration of essential oils, and that the exact composition of the essential oils differs among the plant parts. To develop new medicines and make full use of the Chaihu(Radix Bupleuri Chinensis)resource, it is important to characterize the essential oils from different parts of the plant. In future research, it will be important to determine the pharmacological effects of the various components and the essential oil mixtures.
基金Natural Science Foundation of Heilongjiang Province Project:Study on the Protective Effect of Tongqiao Mingmu No.4 on Retinal RGCs in Glaucoma based on Mitochondrial Apoptosis Pathway (No.QC2018115)Special Scientific Research Project of Henan Clinical Research Base of Traditional Chinese Medicine Project:Study on the Mechanism of Tongqiao Mingmu Decoction in the Treatment of Glaucomatous Optic Nerve Atrophy Based on p53-SLC7A11 Mediated RGC Ferroptosis to Regulate Microglial Cell Polarization (No.2022ZDZX127)
文摘OBJECTIVE:To investigate the bioactive compounds of Chaihu(Radix Bupleuri Chinensis)(RB)on glaucomatous optic atrophy(GOA),and to study the pharmacological mechanism.METHODS:We collected information on the bioactive compounds of RB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Targets related to bioactive compounds and GOA were also obtained.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and network analyses were performed to investigate the potential mechanism of RB against GOA.Subsequently,the main bioactive compounds of RB and targets of GOA were docked by Autodock software.Moreover,a GOA model of retinal ganglion cells(RGCs)induced by cobalt chloride was established to verify the effect of RB on GOA.RESULTS:There were 17 main bioactive compounds and 46 key targets were screened as potential players in GOA.The compound-target network mainly contained 17 compounds and 46 corresponding targets,and the key targets consisted of interleukin-6(IL-6),hypoxia inducible factor-1α(HIF1A),Caspase-3,estrogen receptor alpha(ESR1),MYC proto-oncogene(MYC),and vascular endothelial growth factor A(VEGFA).Forty-nine significantly enriched GO terms,and 134 KEGG signaling pathways were identified(P<0.05),including HIF-1,tumor necrosis factor,VEGF,prolaction,and other signaling pathways.Molecular docking results showed that the main bioactive compounds of RB exhibited the strongest binding activity with IL-6.Furthermore,experimental validation showed that the RB extract inhibited the activity and promoted apoptosis of RGCs in a dose-dependent manner.The RB extract also suppressed the expression of Bax,Caspase-3,and Caspase-9 and regulated malonaldehyde,superoxide dismutase,and glutathione peroxide by inhibiting the IL-6/HIF-1αsignaling pathway.CONCLUSIONS:The present study provided insights into the mechanism of RB on GOA.RB mainly reverses GOA by inhibiting the IL-6/HIF-1αsignaling pathway.
基金supported by State Project for Essential Drug Research and Development of China(No.20152X09303001)
文摘We investigated the potential hepatoprotective effect of Radix Bupleuri(RB) by inducing acute liver injury(ALI) in an animal model using acetaminophen(APAP) after pretreatment with RB aqueous extract for three consecutive days. Compared to those of the APAP group, the biochemical and histological results of the RB pretreatment group showed lower serum aspartate transaminase(AST) and alanine transaminase(ALT) levels as well as less liver damage. Pharmacokinetic study of the toxicity related marker acetaminophen-cysteine(APC) revealed a lower exposure level in rats, suggesting that RB alleviated APAP-induced liver damage by preventing glutathione(GSH) depletion. The results of cocktail approach showed significant inhibition of CYP2 E1 and CYP3 A activity. Further investigation revealed the increasing of CYP2 E1 and CYP3 A protein was significantly inhibited in pretreatment group,while no obvious effect on gene expression was found. Therefore, this study clearly demonstrates that RB exhibited significant protective action against APAP-induced acute live injury via pretreatment, and which is partly through inhibiting the increase of activity and translation of cytochrome P450 enzymes, rather than gene transcription.
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.
文摘目的基于代谢组学,多元统计分析和网络药理学方法分析鉴定南北柴胡代谢物差异并分析造成二者临床疗效不同的物质基础。方法通过超高效液相色谱-质谱(Ultra Performance Liquid Chromatography-Mass Spectrometry,UPLC-MS)和气相色谱-质谱(Gas Chromatography-Mass Spectrometry,GC-MS)两种分析技术获得南北柴胡的代谢物,采用主成分分析(Principal Component Analysis,PCA)、聚类分析(Cluster Analysis,CA)和正交偏最小二乘判别分析(Orthogonal Partial Least Squares Discriminant Analysis,OPLS-DA)筛选南北柴胡差异代谢物,通过中药系统药理学数据库分析平台(Traditional Chinese Medicine System Pharmacology Database and Analysis Platform,TCMSP)筛选南北柴胡中的关键活性成分,预测其可能治疗的疾病。结果在两种柴胡中共检测到1733个代谢物,其中有759个为差异代谢物。共筛选出96个关键活性成分,主要包括黄酮类、木脂素和香豆素类、挥发油和萜类化合物。这些关键活性成分与多种靶蛋白相关,对应癌症、肿瘤、心血管疾病、高血压病、炎症、糖尿病、阿兹海默症等多种疾病。结论相较于北柴胡,南柴胡中黄酮和挥发油以及酚酸类成分含量相对较高。研究结果进一步证明了柴胡中除皂苷类成分,其黄酮、香豆素、挥发油、酚酸等成分也可能发挥了重要的药理作用。南北柴胡药效物质基础存在差异,其发挥药效各有不同,因此在临床中若能实现区分用药,对柴胡药用资源实现最大化利用具有重要意义。
