Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the different...Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.展开更多
Standardized Ginkgo biloba leaf extract has been used in clinical trials for its beneficial effects on brain func- tions, particularly in dementia. Substantial experimental evidences indicated that Ginkgo biloba leaf ...Standardized Ginkgo biloba leaf extract has been used in clinical trials for its beneficial effects on brain func- tions, particularly in dementia. Substantial experimental evidences indicated that Ginkgo biloba leaf extract （EGB） protected neuronal cells from a variety of insults. We investigated the effect of EGB on cognitive ability and protein kinase B （PKB） activity in hippocampal neuronal cells of dementia model rats. Rats received an intra- peritoneal injection of D-galactose to induce dementia. Forty-eight Spraque-Dawley rats were randomly divided into six groups, including the control group, D-galactose group （Gal）, low-dose EGB group （EGB-L）, mid-dose EGB group （EGB-M）, high-dose EGB group （EGB-H） and treatment group. The EGB-L, EGB-M and EGB-H groups were administered with EGB and D-galactose simultaneously. Y-maze, cresyl violet staining, TUNEL assays and immunohistochemistry staining were performed to detect learning and memory abilities, morpho- logical changes in the hippocampus, neuronal apoptosis and the expressing level of phospho-PKB, respectively. Rats in the Gal group showed decreased abilities of learning and memory, and hippocampal pyramidal cell layer was damaged, while EGB administration improved learning and memory abilities. The Gal group exhibited many stained, condensed nuclei and micronuclei, either isolated or within the cytoplasm of cells （39.5 ± 1.4）. Apoptotic cells decreased in the groups of EGB-L （35.9±0.9）, EGB-M （16.8± 1.0） and EGB-H （10.1±0.8）, and there were statistical significances compared with the Gal group. Immunoreactivity of phospho-PKB was localized diffusely throughout the cytosol of cells in all groups, while the immunoreactivity of the Gal group was weak. EGB signifi- cantly attenuated learning and memory impairment in a dose-dependent manner, while it could decrease the nmber of TUNEL-positive cells, and increase the activity of PKB. Our results demonstrated that EGB attenuated memory impairment and cell apoptosis in galactose-induced dementia model rats by activating PKB.展开更多
Background： Hyperbaric oxygen （HBO） and Ginkgo biloba extract （e.g., EGB 761） were shown to ameliorate cognitive and memory impairment in Alzheimcr＇s disease （AD）. However, the exact mechanism remains elusive....Background： Hyperbaric oxygen （HBO） and Ginkgo biloba extract （e.g., EGB 761） were shown to ameliorate cognitive and memory impairment in Alzheimcr＇s disease （AD）. However, the exact mechanism remains elusive. The aim of the present study was to investigate the possible mechanisms of HBO and EGB 761 via the function of nuclear factor kappa-B （NF-κB） pathway. Methods： AD rats were induced by injecting β-amyloid 25-35 into the hippocampus. All animals were divided into six groups： Normal. sham. AD model, HBO （2 atmosphere absolute： 60 min/d）, EGB 761 （20 mg·kg^-1 ·d ^-1）, and HBO/EGB 761 groups. Morris water maze tests were used to assess cognitive, and memory capacities of rats： TdT-mediated dUTP Nick-End Labeling staining and Western blotting were used to analyze apoptosis and NF-κB pathway-related proteins in hippocampus tissues. Results： Morris water maze tests revealed that EGB 761 and HBO significantly improved the cognitive and memory ability of AD rats. In addition, the protective effect of combinational therapy （HBO/EGB 761 ） was superior to either HBO or EGB 761 alone. In line. redticed apoptosis with NF-κB pathway activation was observed in hippocampus neurons treated by HBO and EGB 761. Conclusions： Our results suggested that HBO and EGB 761 improve cognitive and memory capacity in a rat model of AD. The protective effects are associated with the reduced apoptosis with NF-κB pathway activation in hippocampus neurons.展开更多
Acute ischemic stroke （AIS）, as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effec...Acute ischemic stroke （AIS）, as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract （GBE） against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell- astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B （GB）, against oxygenglucose deprivation/reoxygenation and glucose （OGD/R） injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein （Na-F）, and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.展开更多
Objective:To investigate the effect of pomegranate peel aqueous extract(PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcux granulosus protoscoleces,and the immunomodu...Objective:To investigate the effect of pomegranate peel aqueous extract(PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcux granulosus protoscoleces,and the immunomodulatory properties of PGE.Methods:Swiss mice were inoculated intraperitoneally with viable protoscoleces.Then,PGE was orally administered daily during cystic echinococcosis development.Cyst development and hepatic damage were macroscopically and histologically analyzed.The production of nitric oxide and TNF-α was assessed in plasma and the hepatic expression of iNOS.TNF-α,NF-κB and CD68 was examined.Moreover,protoscoleces were cultured and treated with different concentrations of PGE.Results:It was observed that in vitro treatment of protoscoleces caused a significant decrease in viability in a PGE-dose-dependent manner.In vivo,after treatment of cystic echinococcosis infected mice with PGE,a significant decrease in nitric oxide levels(P<0.000 1)and TNF-α levels(P<0.001) was observed.This decline was strongly related to the inhibition of cyst development(rate of hydatid cyst growth inhibition=63.08%) and a decrease in CD68 expression in both the pericystic layer of hepatic hydatid cysts and liver tissue(P<0.000 1).A significant diminution of iNOS,TNF-α and NF-κB expression was also observed in liver tissue of treated mice(P<0.000 1).Conclusions:Our results indicate an antihydatic scolicidal effect and immunomodulatory properties of PGE,suggesting its potential therapeutic role against Echinococcuss granulosus infection.展开更多
In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury(ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract(12 and 24 ...In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury(ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract(12 and 24 mg·kg-1) and dexamethasone(2 mg·kg-1), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid(BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase(SOD) and myeloperoxidase(MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α, interleukin-1β, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg-1 markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.展开更多
基金funded by the National Natural Science Foundation of China,No.81501185(to CR)the Key Research&Development Project of Shandong Province of China,No.2017GSF218043(to CR)the Science and Technology Planning Project of Yantai of China,No.2016WS017(to LNG),2017WS105(to HL)
文摘Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.
文摘Standardized Ginkgo biloba leaf extract has been used in clinical trials for its beneficial effects on brain func- tions, particularly in dementia. Substantial experimental evidences indicated that Ginkgo biloba leaf extract （EGB） protected neuronal cells from a variety of insults. We investigated the effect of EGB on cognitive ability and protein kinase B （PKB） activity in hippocampal neuronal cells of dementia model rats. Rats received an intra- peritoneal injection of D-galactose to induce dementia. Forty-eight Spraque-Dawley rats were randomly divided into six groups, including the control group, D-galactose group （Gal）, low-dose EGB group （EGB-L）, mid-dose EGB group （EGB-M）, high-dose EGB group （EGB-H） and treatment group. The EGB-L, EGB-M and EGB-H groups were administered with EGB and D-galactose simultaneously. Y-maze, cresyl violet staining, TUNEL assays and immunohistochemistry staining were performed to detect learning and memory abilities, morpho- logical changes in the hippocampus, neuronal apoptosis and the expressing level of phospho-PKB, respectively. Rats in the Gal group showed decreased abilities of learning and memory, and hippocampal pyramidal cell layer was damaged, while EGB administration improved learning and memory abilities. The Gal group exhibited many stained, condensed nuclei and micronuclei, either isolated or within the cytoplasm of cells （39.5 ± 1.4）. Apoptotic cells decreased in the groups of EGB-L （35.9±0.9）, EGB-M （16.8± 1.0） and EGB-H （10.1±0.8）, and there were statistical significances compared with the Gal group. Immunoreactivity of phospho-PKB was localized diffusely throughout the cytosol of cells in all groups, while the immunoreactivity of the Gal group was weak. EGB signifi- cantly attenuated learning and memory impairment in a dose-dependent manner, while it could decrease the nmber of TUNEL-positive cells, and increase the activity of PKB. Our results demonstrated that EGB attenuated memory impairment and cell apoptosis in galactose-induced dementia model rats by activating PKB.
文摘Background： Hyperbaric oxygen （HBO） and Ginkgo biloba extract （e.g., EGB 761） were shown to ameliorate cognitive and memory impairment in Alzheimcr＇s disease （AD）. However, the exact mechanism remains elusive. The aim of the present study was to investigate the possible mechanisms of HBO and EGB 761 via the function of nuclear factor kappa-B （NF-κB） pathway. Methods： AD rats were induced by injecting β-amyloid 25-35 into the hippocampus. All animals were divided into six groups： Normal. sham. AD model, HBO （2 atmosphere absolute： 60 min/d）, EGB 761 （20 mg·kg^-1 ·d ^-1）, and HBO/EGB 761 groups. Morris water maze tests were used to assess cognitive, and memory capacities of rats： TdT-mediated dUTP Nick-End Labeling staining and Western blotting were used to analyze apoptosis and NF-κB pathway-related proteins in hippocampus tissues. Results： Morris water maze tests revealed that EGB 761 and HBO significantly improved the cognitive and memory ability of AD rats. In addition, the protective effect of combinational therapy （HBO/EGB 761 ） was superior to either HBO or EGB 761 alone. In line. redticed apoptosis with NF-κB pathway activation was observed in hippocampus neurons treated by HBO and EGB 761. Conclusions： Our results suggested that HBO and EGB 761 improve cognitive and memory capacity in a rat model of AD. The protective effects are associated with the reduced apoptosis with NF-κB pathway activation in hippocampus neurons.
文摘Acute ischemic stroke （AIS）, as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract （GBE） against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell- astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B （GB）, against oxygenglucose deprivation/reoxygenation and glucose （OGD/R） injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein （Na-F）, and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.
文摘Objective:To investigate the effect of pomegranate peel aqueous extract(PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcux granulosus protoscoleces,and the immunomodulatory properties of PGE.Methods:Swiss mice were inoculated intraperitoneally with viable protoscoleces.Then,PGE was orally administered daily during cystic echinococcosis development.Cyst development and hepatic damage were macroscopically and histologically analyzed.The production of nitric oxide and TNF-α was assessed in plasma and the hepatic expression of iNOS.TNF-α,NF-κB and CD68 was examined.Moreover,protoscoleces were cultured and treated with different concentrations of PGE.Results:It was observed that in vitro treatment of protoscoleces caused a significant decrease in viability in a PGE-dose-dependent manner.In vivo,after treatment of cystic echinococcosis infected mice with PGE,a significant decrease in nitric oxide levels(P<0.000 1)and TNF-α levels(P<0.001) was observed.This decline was strongly related to the inhibition of cyst development(rate of hydatid cyst growth inhibition=63.08%) and a decrease in CD68 expression in both the pericystic layer of hepatic hydatid cysts and liver tissue(P<0.000 1).A significant diminution of iNOS,TNF-α and NF-κB expression was also observed in liver tissue of treated mice(P<0.000 1).Conclusions:Our results indicate an antihydatic scolicidal effect and immunomodulatory properties of PGE,suggesting its potential therapeutic role against Echinococcuss granulosus infection.
基金supported by the National Science and Technology Support Program of China(No.2011BAI 04B03)
文摘In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury(ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract(12 and 24 mg·kg-1) and dexamethasone(2 mg·kg-1), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid(BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase(SOD) and myeloperoxidase(MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α, interleukin-1β, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg-1 markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.
