Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity....Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity. However, few studies regarding effects ofOenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract ofOenanthe javanica on cell proliferation and neu-roblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 （an endogenous marker for cell proliferation） and doublecortin （a marker for neuroblast）. Our results showed thatOenanthe javanica extract signiifcantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was signiifcantly increased in the dentate gyrus of the Oenanthe javanica extract-treated group compared with the control group. However, we did not ifnd that vascular endothelial growth factor expression was increased in theOenanthe javanica extract-treated group compared with the control group. These results indicate thatOenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-de-rived neurotrophic factor immunoreactivity in the rat dentate gyrus.展开更多
Following ischemic stroke, blood-brain barrier （BBB） is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown promotes inflammation infiltration into the brain, which ...Following ischemic stroke, blood-brain barrier （BBB） is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown promotes inflammation infiltration into the brain, which exacerbates cerebral ischemic injury as a result. Here, we report that 10-O-（N,N-dimethylaminoethyl）-ginkgolide B methanesulfonate （XQ-1H） , a novel analog of ginkgolide B, alleviates BBB breakdown in hyperlipidemic rats and protects endothelial cells against inflammatory response. Middle cerebral artery occlusion （MCAO） modeled is- chemic stroke in rats. Before surgery, these rats were fed a cholesterol-rich diet to induce an experimental hyperlip- idemic condition. Additionally, lipopolysaccharide （LPS） incubation with rat brain microvessel endothelial cells （rBMECs） was applied to mimic hyperlipidemia-induced inflammatory injury of BBB. The results indicated more severe infarct size, increased BBB permeability, excessive secretion of pro-inflammatory cytokines, and exaggerated inflammation infiltration of the brain in hyperlipidemic rats following MCAO when compared to rats fed with normal diet. XQ-1H protected BBB integrity, lessoned brain edema and inflammation penetration, down- regulated MMP- 9 and VCMA-1 expressions, and extenuated ischemic infarction. XQ-1H alleviated LPS-induced inflammatory re- sponse in rBMECs, characterized by promoting cell viability, inhibiting TNF-α, IL-1β, and IL-6 releasing, and downregulating NF-KB inflammatory signal and down- stream proteins, such as VCAM-1 and iNOS. In conclusion, the present study shows that XQ-1H stabilizes BBB function following ischemic stroke in hyperlipidemic rats, and the possible mechanisms may be related to inflammation inhibition.展开更多
Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divid...Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divided into 6 groups:control group,oxygen and glucose deprivation(OGD)group,nimodipine group(9.375 mg/kg),NXTC group(0.5 g/kg),GHI group(5 mL/kg)and NXTC+GHI group(0.5 g/kg NXTC+5 mL/kg GHI),after the onset of reperfusion and once per day for the following 7 days.Blood was collected 1 h after final administration,and the sera were collected.Cultured primary rat brain microvascular endothelial cells(rBMECs)were subjected to OGD to establish a cell injury model.Untreated rBMECs were used as blank control.The cell counting kit-8 assay was used to assess cell viability using the sera.Malondialdehyde(MDA)and superoxide dismutase(SOD)levels were assessed using an enzyme-linked immunosorbent assay.Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry.JC-1 staining was performed to assess changes in mitochondrial membrane potential.Results:Statistical analysis indicated that more than 95%of the cells were rBMECs.Compared with the OGD group,the cellular morphology of the all drug delivery groups improved.In particular,the combined drug group had the most significant effect.Compared with the OGD group,all drug intervention groups induced a decrease in the apoptotic rate of rBMECs,increased the SOD levels,and decreased the MDA levels(all P<0.01).Compared with the mono-therapy groups,the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs(P<0.01).All drug intervention groups showed different degrees of increase in membrane potential,and the NXTC+GHI group was higher than the NXTC or GHI group(P<0.01).Conclusion:The combinationa application of NXTC and GHI on cerebral l/R injury clearly resulted in protective benefits.展开更多
目的探讨映山红花总黄酮(total flavones of rhododendra,TFR)促大鼠脑血管内皮细胞体外形成血管作用及与VEGFR_(2)和神经源性硫化氢(H_(2)S)的关系。方法采用大鼠脑血管内皮细胞单独培养及和与海马神经元共培养,分别采用不同的实验方...目的探讨映山红花总黄酮(total flavones of rhododendra,TFR)促大鼠脑血管内皮细胞体外形成血管作用及与VEGFR_(2)和神经源性硫化氢(H_(2)S)的关系。方法采用大鼠脑血管内皮细胞单独培养及和与海马神经元共培养,分别采用不同的实验方法检测细胞增殖、迁移、成管及H_(2)S含量和钙离子荧光强度,包括CCK-8法、细胞划痕法、Transwell法、基质胶成管、H_(2)S试剂盒及钙离子荧光探针法。结果在单独培养的大鼠脑血管内皮细胞上,H_(2)S供体NaHS(200μmol·L^(-1))和TFR(90、270、810 mg·L^(-1))对大鼠脑血管内皮细胞的增殖、迁移、成管及[Ca^(2+)]i荧光强度都有明显的促进作用。而VEGFR_(2)阻断剂SU5416(10μmol·L^(-1))可抑制TFR的促进内皮细胞增殖、迁移和形成血管及[Ca^(2+)]i荧光强度;在与海马神经元共培养的大鼠脑血管内皮细胞上,TFR显著地升高共培养中H_(2)S含量,并被CBS抑制剂AOAA(200μmol·L^(-1))抑制。与此同时,TFR明显地促进共培养中大鼠脑血管内皮细胞的形成血管作用,并可被AOAA和VEGFR_(2)阻断剂SU5416显著地抑制。结论TFR在体外可通过VEGFR_(2)升高[Ca^(2+)]i来促进脑血管内皮细胞形成血管,并可通过诱导神经元中CBS生成H_(2)S作用于大鼠脑血管内皮细胞的VEGFR_(2)来促进血管形成。展开更多
基金supported by Hallym University Specialization Fund,No.HRF-S-12
文摘Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity. However, few studies regarding effects ofOenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract ofOenanthe javanica on cell proliferation and neu-roblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 （an endogenous marker for cell proliferation） and doublecortin （a marker for neuroblast）. Our results showed thatOenanthe javanica extract signiifcantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was signiifcantly increased in the dentate gyrus of the Oenanthe javanica extract-treated group compared with the control group. However, we did not ifnd that vascular endothelial growth factor expression was increased in theOenanthe javanica extract-treated group compared with the control group. These results indicate thatOenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-de-rived neurotrophic factor immunoreactivity in the rat dentate gyrus.
文摘Following ischemic stroke, blood-brain barrier （BBB） is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown promotes inflammation infiltration into the brain, which exacerbates cerebral ischemic injury as a result. Here, we report that 10-O-（N,N-dimethylaminoethyl）-ginkgolide B methanesulfonate （XQ-1H） , a novel analog of ginkgolide B, alleviates BBB breakdown in hyperlipidemic rats and protects endothelial cells against inflammatory response. Middle cerebral artery occlusion （MCAO） modeled is- chemic stroke in rats. Before surgery, these rats were fed a cholesterol-rich diet to induce an experimental hyperlip- idemic condition. Additionally, lipopolysaccharide （LPS） incubation with rat brain microvessel endothelial cells （rBMECs） was applied to mimic hyperlipidemia-induced inflammatory injury of BBB. The results indicated more severe infarct size, increased BBB permeability, excessive secretion of pro-inflammatory cytokines, and exaggerated inflammation infiltration of the brain in hyperlipidemic rats following MCAO when compared to rats fed with normal diet. XQ-1H protected BBB integrity, lessoned brain edema and inflammation penetration, down- regulated MMP- 9 and VCMA-1 expressions, and extenuated ischemic infarction. XQ-1H alleviated LPS-induced inflammatory re- sponse in rBMECs, characterized by promoting cell viability, inhibiting TNF-α, IL-1β, and IL-6 releasing, and downregulating NF-KB inflammatory signal and down- stream proteins, such as VCAM-1 and iNOS. In conclusion, the present study shows that XQ-1H stabilizes BBB function following ischemic stroke in hyperlipidemic rats, and the possible mechanisms may be related to inflammation inhibition.
基金the National Natural Science Foundation of China(No.81630105,81973560)Zhejiang Provincial Natural Science Foundation of China(Nos.LZ17H270001,LZ18H270001)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents。
文摘Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divided into 6 groups:control group,oxygen and glucose deprivation(OGD)group,nimodipine group(9.375 mg/kg),NXTC group(0.5 g/kg),GHI group(5 mL/kg)and NXTC+GHI group(0.5 g/kg NXTC+5 mL/kg GHI),after the onset of reperfusion and once per day for the following 7 days.Blood was collected 1 h after final administration,and the sera were collected.Cultured primary rat brain microvascular endothelial cells(rBMECs)were subjected to OGD to establish a cell injury model.Untreated rBMECs were used as blank control.The cell counting kit-8 assay was used to assess cell viability using the sera.Malondialdehyde(MDA)and superoxide dismutase(SOD)levels were assessed using an enzyme-linked immunosorbent assay.Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry.JC-1 staining was performed to assess changes in mitochondrial membrane potential.Results:Statistical analysis indicated that more than 95%of the cells were rBMECs.Compared with the OGD group,the cellular morphology of the all drug delivery groups improved.In particular,the combined drug group had the most significant effect.Compared with the OGD group,all drug intervention groups induced a decrease in the apoptotic rate of rBMECs,increased the SOD levels,and decreased the MDA levels(all P<0.01).Compared with the mono-therapy groups,the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs(P<0.01).All drug intervention groups showed different degrees of increase in membrane potential,and the NXTC+GHI group was higher than the NXTC or GHI group(P<0.01).Conclusion:The combinationa application of NXTC and GHI on cerebral l/R injury clearly resulted in protective benefits.
文摘目的探讨映山红花总黄酮(total flavones of rhododendra,TFR)促大鼠脑血管内皮细胞体外形成血管作用及与VEGFR_(2)和神经源性硫化氢(H_(2)S)的关系。方法采用大鼠脑血管内皮细胞单独培养及和与海马神经元共培养,分别采用不同的实验方法检测细胞增殖、迁移、成管及H_(2)S含量和钙离子荧光强度,包括CCK-8法、细胞划痕法、Transwell法、基质胶成管、H_(2)S试剂盒及钙离子荧光探针法。结果在单独培养的大鼠脑血管内皮细胞上,H_(2)S供体NaHS(200μmol·L^(-1))和TFR(90、270、810 mg·L^(-1))对大鼠脑血管内皮细胞的增殖、迁移、成管及[Ca^(2+)]i荧光强度都有明显的促进作用。而VEGFR_(2)阻断剂SU5416(10μmol·L^(-1))可抑制TFR的促进内皮细胞增殖、迁移和形成血管及[Ca^(2+)]i荧光强度;在与海马神经元共培养的大鼠脑血管内皮细胞上,TFR显著地升高共培养中H_(2)S含量,并被CBS抑制剂AOAA(200μmol·L^(-1))抑制。与此同时,TFR明显地促进共培养中大鼠脑血管内皮细胞的形成血管作用,并可被AOAA和VEGFR_(2)阻断剂SU5416显著地抑制。结论TFR在体外可通过VEGFR_(2)升高[Ca^(2+)]i来促进脑血管内皮细胞形成血管,并可通过诱导神经元中CBS生成H_(2)S作用于大鼠脑血管内皮细胞的VEGFR_(2)来促进血管形成。
