Salvianolic acid A （SAA） is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The pr...Salvianolic acid A （SAA） is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier （BBB） through matrix metallopeptidase 9 （MMP-9） inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion （MCAO） for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg.kg-l. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 （TIMP-1） to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.展开更多
Atractylenolide Ⅲ(ATL-Ⅲ), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuropr...Atractylenolide Ⅲ(ATL-Ⅲ), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-Ⅲ on corticosterone injured rat phaeochromocytoma(PC12) cells. Our results demonstrate that ATL-Ⅲ increases cell viability and reduces the release of lactate dehydrogenase(LDH). The results suggest that ATL-Ⅲ protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca^(2+) overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-κB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-Ⅲ protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-Ⅲ may serve as a therapeutic agent in the treatment of depression.展开更多
Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known ...Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in Hep G2 cells was assayed along with the q PCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program Lib Dock of Discovery Studio 2018 software. The results showed that puerarin improved Hep G2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.展开更多
Excess accumulation of white adipose tissue(WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwid...Excess accumulation of white adipose tissue(WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke,heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige(brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue(BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products(alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes(T2 DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.展开更多
OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,t...OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,the rats with chronic cerebral ischemia were randomly divied into three groups:model group,KAE 10 and 30 mg·kg-1group.Another group rats without occlusion of common carotid arteries were used as the sham-operation group.Memory behavior was investigated by Morris water maze test.Prehensile ability was investigated by prehensile traction test.The structure of hippocampus and cortex neurons was observed with Nissel staining.In addition,the SOD activity and MDA content in brain tissue were determined.The DJ-1protein level was determined by Western blotting.RESULTS KAE 10 and 30 mg·kg-1could significantly improve cognitive impairment and prehensile traction ability(P<0.01)induced by chronic cerebral ischemia in rats.The results of the pathological analysis also suggested that KAE could ameliorate the pathological damage induced by chronic cerebral ischemia.In addition,KAE 30 mg·kg-1significantly increased the activity of SOD(P<0.05),but had no effect on the content of MDA in rat brain tissue.Western-blotting confirmed that KAE 10 and30 mg·kg-1could increase the expression of anti-oxidation proteins DJ-1 in hippocampus(P<0.01).CONCLUSION KAE may attenuate the chronic cerebral ischemic injury in rats.展开更多
OBJECTIVE To investigate the effects of salvianolic acid A(SAA)in systemic lupus erythematosus(SLE)induced by pristane in BALB/c mice,this study was performed.METHODS Lupus mice were established by confirming elevated...OBJECTIVE To investigate the effects of salvianolic acid A(SAA)in systemic lupus erythematosus(SLE)induced by pristane in BALB/c mice,this study was performed.METHODS Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.Micewere then treated with daily oral doses of SAA for 5months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E)and periodic acid-Schiff(PAS)staining.Western blot analysis of renal tissue was also employed.RESULTS SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.CONCLUSION The results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.展开更多
OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropr...OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.展开更多
OBJECTIVE To explore whether J24924could prevent the development of pristane-induced lupus in a mouse model,and whether it could protect renal and lower the cardiovascular risk.METHODS The effect of J24924 was assesse...OBJECTIVE To explore whether J24924could prevent the development of pristane-induced lupus in a mouse model,and whether it could protect renal and lower the cardiovascular risk.METHODS The effect of J24924 was assessed in female BALB/c mice intraperitoneal injected with 0.5 m L of pristane,and serum autoantibodies were tested every month,blood pressure wasmeasured every 2 months,while serum inflammatory markers,spleen pathologic characteristics,renal injury and vascular function were observed at 6 month.RESULTS J24924 could decrease serum autoantibodies and serum inflammatory markers in the SLE mice and improved the spleen pathologic characteristics,and at the same time improved the renal injury and decreased inflammatory responses in kidneys,reduced blood pressure and improved vascular endothelial function.Western blotting assays revealed that inhibition for the activation of NF-κB and Rho/ROCKs signaling pathways and the downstream signaling molecules might be the potential mechanisms of J24924.CONCLUSION Our findings suggestthat therapy of J24924 may be a strategy to prevent SLE and ameliorate associated kidney and cardiovascular complications.展开更多
OBJECTIVE Salvianolic acid A(SAA),a polyphenols acid,is a bioactive ingredient from a traditional Chinese medicine named Danshen(Salvia Miltiorrhiza Bunge).According to previous studies,it was shown to possess various...OBJECTIVE Salvianolic acid A(SAA),a polyphenols acid,is a bioactive ingredient from a traditional Chinese medicine named Danshen(Salvia Miltiorrhiza Bunge).According to previous studies,it was shown to possess various effects such as anti-oxidative stress,anti-diabetic complications and anti-pulmonary hypertension.This study is aimed to investigate the effect of SAA on pulmonary arterial endothelial-mesenchymal transition(endoMT)induced by hypoxia and the underlying mechanisms.METHODS Primary cultured human pulmonary arterial endothelial cells(HPAECs)were exposed to 1%O2 for 48 h with or without SAA treatment.RESULTS SAA treatment improved the morphology of HPAECs and inhibited the cytoskeleton remodeling and reduced migration distances.It was observed that the produc⁃tion of ROS in cells was significantly reduced by the treatment of SAA.Meanwhile,SAA alleviated the loss of CD31 and slightly inhibited the expression ofα-SMA.The mechanisms study shows that SAA treatment increased the phosphoryla⁃tion levels of Smad1/5,but inhibited that of Smad2/3.Furthermore,SAA attenuated the phosphorylation levels of ERK and Cofilin,which were enhanced by hypoxia.CONCLUSION SAA treatment can protect HPAECs from endoMT induced by hypoxia,which may perform via the downstream effectors of BMPRs or TGFβR including Smads,ERK and ROCK/cofilin pathways.展开更多
OBJECTIVE To explore the efficacy and mechanism of withaferin A(WA)in Glioblastoma multiforme(GBM,WHO gradeⅣastrocytoma).METHODS Cell viability assay and nude mice xenograft model were used to evaluate the efficacy o...OBJECTIVE To explore the efficacy and mechanism of withaferin A(WA)in Glioblastoma multiforme(GBM,WHO gradeⅣastrocytoma).METHODS Cell viability assay and nude mice xenograft model were used to evaluate the efficacy of WA in GBM.Flow cytometry was performed to detection the effects of WA on apoptosis and cell cycle of GBM.Western blotting and siRNA transfection were carried out to check signaling pathway induced by WA.RESULTS WA significantly inhibited the growth of GBM in vivo and in vitro.WA treatment triggered the intrinsic apoptosis of GBM cells by upregulating expression of Bim and Bad,and arrested GBM cells at G2/M phase through dephosphorylating Thr161 of CDK1 by activating p53-independent p21 up-regulation.In addition,p21 knockdown restored progress of cell cycle and cell viability by down-regulating the expression of Bad rather than Bim.CONCLUSION WA arrested GBM cells at G2/M phase and triggered the intrinsic apoptosis through p21-Bad axis.展开更多
OBJECTIVE To investigate the effects of ex-tract of Ramulus Cinnamom(RC)against LPS-induced inflammation in microglia.METHODS Activated microglia releases various pro-inflammatory cytokines to induce neuroinflammation...OBJECTIVE To investigate the effects of ex-tract of Ramulus Cinnamom(RC)against LPS-induced inflammation in microglia.METHODS Activated microglia releases various pro-inflammatory cytokines to induce neuroinflammation in stroke.Lipopolysaccaride(LPS)is an endotoxin from the outer membrane of Gram-negative bacteria that activates microglia.MTT assay was used to observe the cell viability.The content of NO in supernatant was measured by Griess reagent.The levels of IL-1β,IL-6 and TNF-αin supernatant were detected by ELISA kits.The intracellular COX-2,TLR4,and My D88expression was assayed by Western blotting.RESULTS RC extract 30 and 100μg·m L-1significantly decreased the production of related inflammatory factors such as NO(P<0.05,P<0.01),IL-1β(P<0.01,P<0.01),IL-6(P<0.05,P<0.01)and TNF-α(P<0.01,P<0.01).Furthermore,RC extract significantly inhibited the COX-2,TLR4,and My D88 expression induced by LPS in BV2cells.CONCLUSION RC extract may have therapeutic potential for the improvement of neuroinflammation,and the mechanism may be involved in down-regulation of TLR4/My D88 inflammation pathway.展开更多
OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancie...OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancient Tang Dynasty.In our previous study,the active fraction of XXMD(XXM)against cerebral ischemia has been prepared by modern separation and purification techniques.This study was to investigate XXM against lipopolysaccaride(LPS)-induced neuroinflammation in mice.METHODS LPS is an endotoxin from the outer membrane of Gram-negative bacteria that activates inflammation.XXM was pre-treated in BALB/C mice followed by injected intraperitoneally with LPS(5 mg·kg-1).The effects of XXM on LPS-induced pro-inflammatory factors and proteins were measured by ELISA,Western blot,and immunofluorescence in vivo.RESULTS Mice treated with XXM showed significantly decreased proinflammatory factors level,including IL-1β(P<0.01),IL-6(P<0.01),TNF-α(P<0.05),and MCP-1(P<0.01).Furthermore,XXM also significantly inhibited the inflammatory pathway proteins expression induced by LPS,including TLR4,MyD 88,and COX-2.CONCLUSION XXM possesses anti-neuroinflammation in mice and might be a promising therapeutic agent for stroke.展开更多
《伏立康唑个体化用药指南》是一部由北京大学第三医院药剂科发起,中国药理学会治疗药物监测研究专业委员会批准制定,由兰州大学推荐分级评估、制定与评价(grading of recommendations assessment, development and evaluation, GRADE)...《伏立康唑个体化用药指南》是一部由北京大学第三医院药剂科发起,中国药理学会治疗药物监测研究专业委员会批准制定,由兰州大学推荐分级评估、制定与评价(grading of recommendations assessment, development and evaluation, GRADE)中国中心提供方法学支持的临床实践指南。该指南于2017年8月被美国国立指南库(National Guideline Clearinghouse, NGC)正式收录,并于2018年12月发表于《Therapeutic Drug Monitoring》杂志。本文为该指南的中文解读版本,涵盖本部指南所有推荐意见、证据及解读,旨在为临床使用伏立康唑提供参考。展开更多
基金supported by the National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(2013ZX09508104 and 2013ZX09402203)the National Natural Science Foundation of China(No.81603100)+1 种基金the open project of State Key Laboratory of Toxicology and Medical Countermeasures(TMC201510)the graduate student innovation fund of Chinese Academy of Medical Sciences and Peking Union Medical College(No.2015-1007-07)
文摘Salvianolic acid A （SAA） is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier （BBB） through matrix metallopeptidase 9 （MMP-9） inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion （MCAO） for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg.kg-l. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 （TIMP-1） to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.
基金supported by the National Nature Science Foundation of China(No.81673572)the Applied basic research project of Shanxi Province(No.201601D021164)+2 种基金the Innovation project of higher education institutions in Shanxi Province(No.2016120)the Construction of the Science and Technology Basic Condition Platform of Shanxi Province(No.2014091022)the Program of Science and Technology of Shanxi Province(No.20140313008-14)
文摘Atractylenolide Ⅲ(ATL-Ⅲ), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-Ⅲ on corticosterone injured rat phaeochromocytoma(PC12) cells. Our results demonstrate that ATL-Ⅲ increases cell viability and reduces the release of lactate dehydrogenase(LDH). The results suggest that ATL-Ⅲ protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca^(2+) overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-κB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-Ⅲ protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-Ⅲ may serve as a therapeutic agent in the treatment of depression.
基金supported by the National Natural Science Foundation of China (No. 81770847)the Drug Innovation Major Project (No. 2018ZX09711001-003-005)+1 种基金the CAMS Innovation Fund for Medical Sciences (CIFMS)(Nos. 2017-I2M-1-010and 2016-I2M-3-007)National Key Research and Development Plan (No. 2016YFC1000905)。
文摘Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in Hep G2 cells was assayed along with the q PCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program Lib Dock of Discovery Studio 2018 software. The results showed that puerarin improved Hep G2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.
基金supported by the National Natural Science Foundation of China (No. 81770847)the Drug Innovation Major Project (No. 2018ZX09711001-003-005)CAMS Innovation Fund for Medical Sciences (No. 2017-I2M-1-010)。
文摘Excess accumulation of white adipose tissue(WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke,heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige(brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue(BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products(alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes(T2 DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.
基金The project supported by National Natural Science Foundation of China(81473383,81573645)
文摘OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,the rats with chronic cerebral ischemia were randomly divied into three groups:model group,KAE 10 and 30 mg·kg-1group.Another group rats without occlusion of common carotid arteries were used as the sham-operation group.Memory behavior was investigated by Morris water maze test.Prehensile ability was investigated by prehensile traction test.The structure of hippocampus and cortex neurons was observed with Nissel staining.In addition,the SOD activity and MDA content in brain tissue were determined.The DJ-1protein level was determined by Western blotting.RESULTS KAE 10 and 30 mg·kg-1could significantly improve cognitive impairment and prehensile traction ability(P<0.01)induced by chronic cerebral ischemia in rats.The results of the pathological analysis also suggested that KAE could ameliorate the pathological damage induced by chronic cerebral ischemia.In addition,KAE 30 mg·kg-1significantly increased the activity of SOD(P<0.05),but had no effect on the content of MDA in rat brain tissue.Western-blotting confirmed that KAE 10 and30 mg·kg-1could increase the expression of anti-oxidation proteins DJ-1 in hippocampus(P<0.01).CONCLUSION KAE may attenuate the chronic cerebral ischemic injury in rats.
基金The project supported by National Natural Science Foundation of China(81573645,81673422)
文摘OBJECTIVE To investigate the effects of salvianolic acid A(SAA)in systemic lupus erythematosus(SLE)induced by pristane in BALB/c mice,this study was performed.METHODS Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.Micewere then treated with daily oral doses of SAA for 5months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E)and periodic acid-Schiff(PAS)staining.Western blot analysis of renal tissue was also employed.RESULTS SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.CONCLUSION The results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.
基金The project supported by National Natural Science Foundation of China(81573645,81603101,81473383)
文摘OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.
基金The project supported by National Science and Technology Major Project(2013ZX09103001-008,2013ZX09402203)the National Natural Science Foundation of China(81573645)
文摘OBJECTIVE To explore whether J24924could prevent the development of pristane-induced lupus in a mouse model,and whether it could protect renal and lower the cardiovascular risk.METHODS The effect of J24924 was assessed in female BALB/c mice intraperitoneal injected with 0.5 m L of pristane,and serum autoantibodies were tested every month,blood pressure wasmeasured every 2 months,while serum inflammatory markers,spleen pathologic characteristics,renal injury and vascular function were observed at 6 month.RESULTS J24924 could decrease serum autoantibodies and serum inflammatory markers in the SLE mice and improved the spleen pathologic characteristics,and at the same time improved the renal injury and decreased inflammatory responses in kidneys,reduced blood pressure and improved vascular endothelial function.Western blotting assays revealed that inhibition for the activation of NF-κB and Rho/ROCKs signaling pathways and the downstream signaling molecules might be the potential mechanisms of J24924.CONCLUSION Our findings suggestthat therapy of J24924 may be a strategy to prevent SLE and ameliorate associated kidney and cardiovascular complications.
基金CAMS Innovation Fund for Medical Sciences(2017-I2M-1-010)National Natural Science Foundation of China(81773935+1 种基金8157364581603101)
文摘OBJECTIVE Salvianolic acid A(SAA),a polyphenols acid,is a bioactive ingredient from a traditional Chinese medicine named Danshen(Salvia Miltiorrhiza Bunge).According to previous studies,it was shown to possess various effects such as anti-oxidative stress,anti-diabetic complications and anti-pulmonary hypertension.This study is aimed to investigate the effect of SAA on pulmonary arterial endothelial-mesenchymal transition(endoMT)induced by hypoxia and the underlying mechanisms.METHODS Primary cultured human pulmonary arterial endothelial cells(HPAECs)were exposed to 1%O2 for 48 h with or without SAA treatment.RESULTS SAA treatment improved the morphology of HPAECs and inhibited the cytoskeleton remodeling and reduced migration distances.It was observed that the produc⁃tion of ROS in cells was significantly reduced by the treatment of SAA.Meanwhile,SAA alleviated the loss of CD31 and slightly inhibited the expression ofα-SMA.The mechanisms study shows that SAA treatment increased the phosphoryla⁃tion levels of Smad1/5,but inhibited that of Smad2/3.Furthermore,SAA attenuated the phosphorylation levels of ERK and Cofilin,which were enhanced by hypoxia.CONCLUSION SAA treatment can protect HPAECs from endoMT induced by hypoxia,which may perform via the downstream effectors of BMPRs or TGFβR including Smads,ERK and ROCK/cofilin pathways.
基金China Postdoctoral Science Foundation(2018M640093)National Natural Science Foundation of China(81803584+2 种基金81573454)CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007)National Science and Technology Major Project of China(2018ZX09711001-005-025)
文摘OBJECTIVE To explore the efficacy and mechanism of withaferin A(WA)in Glioblastoma multiforme(GBM,WHO gradeⅣastrocytoma).METHODS Cell viability assay and nude mice xenograft model were used to evaluate the efficacy of WA in GBM.Flow cytometry was performed to detection the effects of WA on apoptosis and cell cycle of GBM.Western blotting and siRNA transfection were carried out to check signaling pathway induced by WA.RESULTS WA significantly inhibited the growth of GBM in vivo and in vitro.WA treatment triggered the intrinsic apoptosis of GBM cells by upregulating expression of Bim and Bad,and arrested GBM cells at G2/M phase through dephosphorylating Thr161 of CDK1 by activating p53-independent p21 up-regulation.In addition,p21 knockdown restored progress of cell cycle and cell viability by down-regulating the expression of Bad rather than Bim.CONCLUSION WA arrested GBM cells at G2/M phase and triggered the intrinsic apoptosis through p21-Bad axis.
基金The project supported by National Natural Science Foundation of China(81473383,81573645)
文摘OBJECTIVE To investigate the effects of ex-tract of Ramulus Cinnamom(RC)against LPS-induced inflammation in microglia.METHODS Activated microglia releases various pro-inflammatory cytokines to induce neuroinflammation in stroke.Lipopolysaccaride(LPS)is an endotoxin from the outer membrane of Gram-negative bacteria that activates microglia.MTT assay was used to observe the cell viability.The content of NO in supernatant was measured by Griess reagent.The levels of IL-1β,IL-6 and TNF-αin supernatant were detected by ELISA kits.The intracellular COX-2,TLR4,and My D88expression was assayed by Western blotting.RESULTS RC extract 30 and 100μg·m L-1significantly decreased the production of related inflammatory factors such as NO(P<0.05,P<0.01),IL-1β(P<0.01,P<0.01),IL-6(P<0.05,P<0.01)and TNF-α(P<0.01,P<0.01).Furthermore,RC extract significantly inhibited the COX-2,TLR4,and My D88 expression induced by LPS in BV2cells.CONCLUSION RC extract may have therapeutic potential for the improvement of neuroinflammation,and the mechanism may be involved in down-regulation of TLR4/My D88 inflammation pathway.
基金The project supported by National Natural Science Foundation of China(81473383,81573645)
文摘OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancient Tang Dynasty.In our previous study,the active fraction of XXMD(XXM)against cerebral ischemia has been prepared by modern separation and purification techniques.This study was to investigate XXM against lipopolysaccaride(LPS)-induced neuroinflammation in mice.METHODS LPS is an endotoxin from the outer membrane of Gram-negative bacteria that activates inflammation.XXM was pre-treated in BALB/C mice followed by injected intraperitoneally with LPS(5 mg·kg-1).The effects of XXM on LPS-induced pro-inflammatory factors and proteins were measured by ELISA,Western blot,and immunofluorescence in vivo.RESULTS Mice treated with XXM showed significantly decreased proinflammatory factors level,including IL-1β(P<0.01),IL-6(P<0.01),TNF-α(P<0.05),and MCP-1(P<0.01).Furthermore,XXM also significantly inhibited the inflammatory pathway proteins expression induced by LPS,including TLR4,MyD 88,and COX-2.CONCLUSION XXM possesses anti-neuroinflammation in mice and might be a promising therapeutic agent for stroke.
文摘《伏立康唑个体化用药指南》是一部由北京大学第三医院药剂科发起,中国药理学会治疗药物监测研究专业委员会批准制定,由兰州大学推荐分级评估、制定与评价(grading of recommendations assessment, development and evaluation, GRADE)中国中心提供方法学支持的临床实践指南。该指南于2017年8月被美国国立指南库(National Guideline Clearinghouse, NGC)正式收录,并于2018年12月发表于《Therapeutic Drug Monitoring》杂志。本文为该指南的中文解读版本,涵盖本部指南所有推荐意见、证据及解读,旨在为临床使用伏立康唑提供参考。
