Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii H...Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.展开更多
[Objectives]To study the inhibitory activity of two flavonoid glycosides isolated from Chlorophytum comosum Laxum R.Br on human nasopharyngeal carcinoma(NPC)cell line 5-8F in vitro and its mechanism.[Methods]The flavo...[Objectives]To study the inhibitory activity of two flavonoid glycosides isolated from Chlorophytum comosum Laxum R.Br on human nasopharyngeal carcinoma(NPC)cell line 5-8F in vitro and its mechanism.[Methods]The flavonoid glycosides were isolated and purified from the ethanol alcoholic extract of the roots of Liliaceae plant Chlorophytum comosum by silica gel column chromatography,macroporous resin column chromatography,Sephadex LH-20,and reverse column chromatography(ODS).The inhibitory activity of flavonoid glycosides on human nasopharyngeal carcinoma cells was analyzed by CCK-8 method,and the potential mechanism was preliminarily analyzed by molecular docking.[Results]Two flavonoid glycosides were identified as isovitexin 2″-0-rhamnoside and 7-2″-di-O-β-glucopyranosylisovitexin.Two flavonoid glycosides showed promising inhibitory effect on human nasopharyngeal carcinoma cell line 5-8F,with IC_(50) values of 24.8 and 27.5μmol/L,respectively.Molecular docking results showed that the potential targets of two flavonoid glycosides include CyclinD1,Bcl-2β-Catenin,ILK,TGF-β,in addition,two glycosides showed higher predicted binding affinity towards CyclinD1,which verifies the cytotoxicity of the two compounds on human nasopharyngeal carcinoma cell line 5-8F in vitro.[Conclusions]Two flavonoid glycosides are the active molecules in Chlorophytum comosum that can inhibit the proliferation of human nasopharyngeal carcinoma cells,and have the potential to be used in the research and development of anti nasopharyngeal carcinoma drugs.展开更多
Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,le...Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.展开更多
Cymbaria daurica L. is a well-known traditional Mongolian medicine, which has been used to treat diabetesrelated conditions characterized by persistent thirst and hunger, copious urination, and weight loss. We aimed t...Cymbaria daurica L. is a well-known traditional Mongolian medicine, which has been used to treat diabetesrelated conditions characterized by persistent thirst and hunger, copious urination, and weight loss. We aimed to investigate the protective effects of C. daurica extracts and phenylethanoid glycosides including verbascoside and isoacteoside on INS-1 cells. We discovered phenylethanoid glycosides from n-butanol extract with large content through extraction and separation. We continue to study the protective effects of phenylethanoid glycosides including verbascoside and isoacteoside on INS-1 cells. INS-1 cells were treated with C. daurica, cell viability assay, RNA-seq technology, superoxide dismutase activity and malonaldehyde content, quantitative real time-PCR and Western blot analysis were used to study the protective effects of C. daurica. Cell viability assay resulted that n-butanol extract and verbascoside, isoacteoside showed protective effects of C. daurica. According to the RNA-seq technology to identify the differentially expressed genes in INS-1 cells, the pathway of gene enrich the protective effect of C. daurica on oxidative stress. SOD activity and the content of MDA indicated that C. daurica could enhance the antioxidant capacity of INS-1 cells. Further investigation indicated C. daurica alleviate oxidative stress by inhibiting INS-1 cell apoptosis. C. daurica may play an anti-diabetic role by inhibiting islet cell apoptosis.展开更多
Objective:To investigate the mechanism of action of tetrahydroxy stilbene glycosides(TSG)in ameliorating neuronal damage in Alzheimer's disease rats by regulating MKK7 and JNK kinases.Methods:A total of 24-month-o...Objective:To investigate the mechanism of action of tetrahydroxy stilbene glycosides(TSG)in ameliorating neuronal damage in Alzheimer's disease rats by regulating MKK7 and JNK kinases.Methods:A total of 24-month-old 42 SD rats were randomly selected for the experiment in 7 groups:normal group,sham-operated group,model group,positive drug group,low,medium and high dose TSG group at 0.033 g/kg,0.1 g/kg,0.3 g/kg.The Model Group and the TSG groups were established by stereotaxic Aβ25-35 solution.After 28 days,the model rats were selected by passive avoidance test.After screening,each dosage group of TSG and positive drug group was given intragastrically according to the corresponding dosage,and the experiment was carried out after 28 days.The pathological changes of hippocampal CA1 region were observed by tissue staining,and the amount of MKK7 and JNK proteins and the expression content of MKK7 and JNK mRNA by histochemical method of protein,and qRTPCR assay.Results:(1)He staining observation:Compared with the normal group and the sham-operated group,the number of nerve cells in the model group decreased and arranged irregularly,the cell membrane shrank,and the nucleus deformed and dissolved.The number of neurons in the positive drug group and TSG Group also increased significantly,the order is also relatively well.(2)From the results of the Tunel staining experiments:the positive apoptotic cells in the model group were higher than control group and sham-operated group,positive drug group and TSG drugs group was significantly smaller than that in the model group(P<0.05).(3)Compared with the control group and the Virtual Operation Group,the MKK7 and JNK protein concentrations in the brain of the model group were increased(P<0.05)by data analysis of immunohistochemistry:Compared with the model group,the protein expression of positive drug and TSG each dose group were reduced(P<0.05).(4)The results of QRTPCR data showed that the levels of MKK7 and JNK mRNA in the brain tissue of the model group were increased compared with the normal group and sham-operated groups(P<0.05).Conclusion:Stilbene glycoside has a certain effect on neuronal injury and repair which may be related to the changes of mRNA transcription and protein expression of MKK7 and JNK kinases.展开更多
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A03807 and CI2021A01501)the National Natural Science Foundation of China(82330124)+2 种基金the Beijing Municipal Natural Science Foundation(7212186)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002)the Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences.
文摘Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.
基金Supported by Youth Fund Project of Zhaoqing University(QZ202235)Zhaoqing Science and Technology Plan Project(2022040311011).
文摘[Objectives]To study the inhibitory activity of two flavonoid glycosides isolated from Chlorophytum comosum Laxum R.Br on human nasopharyngeal carcinoma(NPC)cell line 5-8F in vitro and its mechanism.[Methods]The flavonoid glycosides were isolated and purified from the ethanol alcoholic extract of the roots of Liliaceae plant Chlorophytum comosum by silica gel column chromatography,macroporous resin column chromatography,Sephadex LH-20,and reverse column chromatography(ODS).The inhibitory activity of flavonoid glycosides on human nasopharyngeal carcinoma cells was analyzed by CCK-8 method,and the potential mechanism was preliminarily analyzed by molecular docking.[Results]Two flavonoid glycosides were identified as isovitexin 2″-0-rhamnoside and 7-2″-di-O-β-glucopyranosylisovitexin.Two flavonoid glycosides showed promising inhibitory effect on human nasopharyngeal carcinoma cell line 5-8F,with IC_(50) values of 24.8 and 27.5μmol/L,respectively.Molecular docking results showed that the potential targets of two flavonoid glycosides include CyclinD1,Bcl-2β-Catenin,ILK,TGF-β,in addition,two glycosides showed higher predicted binding affinity towards CyclinD1,which verifies the cytotoxicity of the two compounds on human nasopharyngeal carcinoma cell line 5-8F in vitro.[Conclusions]Two flavonoid glycosides are the active molecules in Chlorophytum comosum that can inhibit the proliferation of human nasopharyngeal carcinoma cells,and have the potential to be used in the research and development of anti nasopharyngeal carcinoma drugs.
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
基金supported by the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(Grant No.:2020YFE0205100)+13 种基金the National Natural Science Foundation of China(Grant Nos.:82104480,82004248,82141001,82274182,82074098,82173914)the Fundamental Research Funds for the Central public welfare research institutes(Grant Nos.:ZZ14-YQ-055,ZZ14-YQ-059,ZZ14-YQ-060,ZXKT19018,ZXKT19021,ZXKT19022,ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10,ZZ16-ND-10-19)the Beijing Municipal Natural Science Foundation(Grant No.:7214287)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-C-202002)the Young Elite Scientists Sponsorship Program by CACM(Grant No.:2021QNRC2B29)the CACMS Innovation Fund(Grant Nos.:CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)the Science and Technology Foundation of Shenzhen(Grant No.:JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases)Shenzhen Governmental Sustainable Development Fund(Grant No.:KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases(Grant No.:ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(Grant No.:SZGSP001)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)the State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process Open Fund(Grant No.:SKL2020Z0302).
文摘Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.
基金funded by the National Natural Science Foundation of China (81760776)the Natural Science Foundation of Inner Mongolia Autonomous Region (2018ZD13)+2 种基金the Natural Science Foundation of Inner Mongolia Autonomous Region (2020MS08070)Science and technology development projects in key areas of Baotou science and technology plan (2020Z1016-3)Natural Science Foundation Project of Inner Mongolia Autonomous Region (2021MS03025)。
文摘Cymbaria daurica L. is a well-known traditional Mongolian medicine, which has been used to treat diabetesrelated conditions characterized by persistent thirst and hunger, copious urination, and weight loss. We aimed to investigate the protective effects of C. daurica extracts and phenylethanoid glycosides including verbascoside and isoacteoside on INS-1 cells. We discovered phenylethanoid glycosides from n-butanol extract with large content through extraction and separation. We continue to study the protective effects of phenylethanoid glycosides including verbascoside and isoacteoside on INS-1 cells. INS-1 cells were treated with C. daurica, cell viability assay, RNA-seq technology, superoxide dismutase activity and malonaldehyde content, quantitative real time-PCR and Western blot analysis were used to study the protective effects of C. daurica. Cell viability assay resulted that n-butanol extract and verbascoside, isoacteoside showed protective effects of C. daurica. According to the RNA-seq technology to identify the differentially expressed genes in INS-1 cells, the pathway of gene enrich the protective effect of C. daurica on oxidative stress. SOD activity and the content of MDA indicated that C. daurica could enhance the antioxidant capacity of INS-1 cells. Further investigation indicated C. daurica alleviate oxidative stress by inhibiting INS-1 cell apoptosis. C. daurica may play an anti-diabetic role by inhibiting islet cell apoptosis.
基金National Natural Science Foundation of China (81860709)Project of Baise City Regional Multiple Development Joint Special Plan[Bai Zi (2022)41-39]。
文摘Objective:To investigate the mechanism of action of tetrahydroxy stilbene glycosides(TSG)in ameliorating neuronal damage in Alzheimer's disease rats by regulating MKK7 and JNK kinases.Methods:A total of 24-month-old 42 SD rats were randomly selected for the experiment in 7 groups:normal group,sham-operated group,model group,positive drug group,low,medium and high dose TSG group at 0.033 g/kg,0.1 g/kg,0.3 g/kg.The Model Group and the TSG groups were established by stereotaxic Aβ25-35 solution.After 28 days,the model rats were selected by passive avoidance test.After screening,each dosage group of TSG and positive drug group was given intragastrically according to the corresponding dosage,and the experiment was carried out after 28 days.The pathological changes of hippocampal CA1 region were observed by tissue staining,and the amount of MKK7 and JNK proteins and the expression content of MKK7 and JNK mRNA by histochemical method of protein,and qRTPCR assay.Results:(1)He staining observation:Compared with the normal group and the sham-operated group,the number of nerve cells in the model group decreased and arranged irregularly,the cell membrane shrank,and the nucleus deformed and dissolved.The number of neurons in the positive drug group and TSG Group also increased significantly,the order is also relatively well.(2)From the results of the Tunel staining experiments:the positive apoptotic cells in the model group were higher than control group and sham-operated group,positive drug group and TSG drugs group was significantly smaller than that in the model group(P<0.05).(3)Compared with the control group and the Virtual Operation Group,the MKK7 and JNK protein concentrations in the brain of the model group were increased(P<0.05)by data analysis of immunohistochemistry:Compared with the model group,the protein expression of positive drug and TSG each dose group were reduced(P<0.05).(4)The results of QRTPCR data showed that the levels of MKK7 and JNK mRNA in the brain tissue of the model group were increased compared with the normal group and sham-operated groups(P<0.05).Conclusion:Stilbene glycoside has a certain effect on neuronal injury and repair which may be related to the changes of mRNA transcription and protein expression of MKK7 and JNK kinases.