Multiple sclerosis(MS),a diseaseaffecting the central nervous system,ischaracterized by patches of demyelinationand sclerosis of gliosis desseminatedthroughout the white matter of brain andspinal cord.In 1968,Charcot ...Multiple sclerosis(MS),a diseaseaffecting the central nervous system,ischaracterized by patches of demyelinationand sclerosis of gliosis desseminatedthroughout the white matter of brain andspinal cord.In 1968,Charcot firstdescribed its clinical and pathologicalcharacteristics.Its incidence is very high,especially in Europe and America.Thereis no epidemic data of this展开更多
Objective： To investigate the neuroprotective effect of Bu-Shen-Huo-Xue （BSHX） extract, a polyherbal formula, against High Glucose （HG）-induced neurotoxicity in PC12 cells. Methods： Cell viability assay, Lactate...Objective： To investigate the neuroprotective effect of Bu-Shen-Huo-Xue （BSHX） extract, a polyherbal formula, against High Glucose （HG）-induced neurotoxicity in PC12 cells. Methods： Cell viability assay, Lactate Dehydrogenase （LDH） assay, Reactive Oxygen Species （ROS） detection, Hoechst 33258, Acridine Orange （AO）/Ethidium Bromide （EB） double stain and Mitochondrial Membrane Potential （MMP） assay were performed. In addition, Bax, Bcl-2, caspase-3, cleaved caspase-3, PARP, cleaved PARP, cytochrome c and Mitogen-Activated Protein Kinases （MAPKs） were detected by western blot. Results： BSHX extract increased cell viability and decreased LDH leakage in a concentration-dependent manner in HG-induced PC12 cells. Moreover, BSHX extract decreased the level of intracellular ROS, increased mitochondrial membrane potential, regulated the expressions of Bax and Bcl-2, and inhibited the release of cytochrome c from mitochondria. Furthermore, BSHX extract attenuated the activation of caspase-3 and PARP, and inhibited the phosphorylations of c-Jun N-terminal kinase （JNK） and p38 MAPKs. Conclusion： BSHX extract exhibited significant neuroprotective effect on HG-induced apoptosis in PC12 cells. This effect may be associated with the suppression of ROS generation as well as mitochondria-mediated caspase and JNK/p38 MAPK signaling pathways.展开更多
OBJECTIVE： To observe the effect of tonifying liver and kidney-essence herbs on expression of a nerve regeneration inhibitor, Nogo for neuron A （No- go-A）, and its associated signaling molecule, low-af- finity neur...OBJECTIVE： To observe the effect of tonifying liver and kidney-essence herbs on expression of a nerve regeneration inhibitor, Nogo for neuron A （No- go-A）, and its associated signaling molecule, low-af- finity neurotrophin receptor p75 （p75TR）, in rats with cerebral ischemic stroke （CIS）, with the aim of exploring the possible mechanism of tonifying liver and kidney-essence herbs in recovery following in- jury to the central nervous system. METHODS： A cerebral ischemic stroke model in SD rats was established with the suture-occlusion method. Successful model rats were divided into placebo and herb groups at random; sham-operat- ed and control groups were set up simultaneously.Each of these groups was divided into six sub- groups at random. Expression of Nogo-A and p75TR was evaluated with immunofluorescence microsco- py at days 3, and weeks1, 2, 3, 4 and 8 after adminis- tration. RESULTS： Tonifying liver and kidney-essence herbs suppressed the expression of Nogo-A and p75T （P〈0.05 and P〈0.01, respectively）. CONCLUSION： Suppressing the expression of No- go-A and p75NTR is possibly one of the mechanisms underlying the ability of tonifying liver and kid- ney-essence herbs to promote recovery of the in- jured central nervous system.展开更多
To investigate the pharmacokinetics of effective components of Bu Yang Huang Wu Decoction(BYHWD)with different dosages of Astragalus(Yiqi groups and Huoxue groups)applicating in rats with middle cerebral artery occlus...To investigate the pharmacokinetics of effective components of Bu Yang Huang Wu Decoction(BYHWD)with different dosages of Astragalus(Yiqi groups and Huoxue groups)applicating in rats with middle cerebral artery occlusion(MCAO).Replicating the animal model of cerebral ischemia-reperfusion in rats,establishing the liquid-mass spectrometry method for the determination of BYHWD and researching the pharmacokinetics of effective components of yiqi groups of BYHWD with different dosages of astragalus(3.09,6.17,12.34 g/Kg)and Huoxue goups(2.32 g/Kg)when applicated seperately in the rats suffering from cerebral ischemia reperfusion injury after femoral vein administration.The pharmacokinetics of formononetin and paeoniflorin in the different dosage groups of BYHWD met the one-compartment model,and the t1/2 of formononetin and paeoniflorin in the low-dose Yiqi and Huoxue groups were(88.43±3.82,69.18±0.11)min,MRT were(138.56±4.83,113.62±2.42)min,and AUC0-twere(28488.35±4800.32,140614.80±23954.05)ng/mL min;The t1/2 of formononetin and paeoniflorin in the middle-dose Yiqi group and Huoxue group were(82.16±1.78,67.08±3.69)min,and MRT were(127.95±2.70,116.58±4.13),AUC0-t were(48619.25±6745.75,159026.00±15003.33)ng/mL min;The t1/2 of formononetin and paeoniflorin in the high-dose Yiqi and Huoxue groups were(80.29±1.12,69.69±0.87)min and MRT was(128.79±1.46,118.78±4.56)min AUC0-twere(109942.90±13101.83,189417.90±22311.00)ng/mL·min.The concentration rate of formononetin t1/2 brain was decreased with increase of Astragalus dose.However,no significant difference between these two variables was found during experiments.Furthermore,the experiments showed that the increasing dose of astragalus would affect the pharmacokinetic behavior of paeoniflorin in the Huoxue groups.More specifically,the result showed that paeoniflorin can be metabolized more slowly in the body when applicated in high dose of the jaundice administration groups.In this way,the effect of paeoniflorin can be lasted for longer time in the body and brain.展开更多
文摘Multiple sclerosis(MS),a diseaseaffecting the central nervous system,ischaracterized by patches of demyelinationand sclerosis of gliosis desseminatedthroughout the white matter of brain andspinal cord.In 1968,Charcot firstdescribed its clinical and pathologicalcharacteristics.Its incidence is very high,especially in Europe and America.Thereis no epidemic data of this
基金This work was supported by the National Natural Science Foundation of China （Grant Nos. 81530099, 81573763 and 81773932）, the Beijing Municipal Natural Science Foundation （Grant No.7172221）, and the National Key Technology R＆D Program ＂New Drug Innovation＂ of China （Grant No. 2016YFE0116200）.
文摘Objective： To investigate the neuroprotective effect of Bu-Shen-Huo-Xue （BSHX） extract, a polyherbal formula, against High Glucose （HG）-induced neurotoxicity in PC12 cells. Methods： Cell viability assay, Lactate Dehydrogenase （LDH） assay, Reactive Oxygen Species （ROS） detection, Hoechst 33258, Acridine Orange （AO）/Ethidium Bromide （EB） double stain and Mitochondrial Membrane Potential （MMP） assay were performed. In addition, Bax, Bcl-2, caspase-3, cleaved caspase-3, PARP, cleaved PARP, cytochrome c and Mitogen-Activated Protein Kinases （MAPKs） were detected by western blot. Results： BSHX extract increased cell viability and decreased LDH leakage in a concentration-dependent manner in HG-induced PC12 cells. Moreover, BSHX extract decreased the level of intracellular ROS, increased mitochondrial membrane potential, regulated the expressions of Bax and Bcl-2, and inhibited the release of cytochrome c from mitochondria. Furthermore, BSHX extract attenuated the activation of caspase-3 and PARP, and inhibited the phosphorylations of c-Jun N-terminal kinase （JNK） and p38 MAPKs. Conclusion： BSHX extract exhibited significant neuroprotective effect on HG-induced apoptosis in PC12 cells. This effect may be associated with the suppression of ROS generation as well as mitochondria-mediated caspase and JNK/p38 MAPK signaling pathways.
基金Suppored by Special Project on Traditional Chinese Medicine Science and Technology of State Administration of Traditional Chinese Medicine of the PRC(No.06-07LB21)
文摘OBJECTIVE： To observe the effect of tonifying liver and kidney-essence herbs on expression of a nerve regeneration inhibitor, Nogo for neuron A （No- go-A）, and its associated signaling molecule, low-af- finity neurotrophin receptor p75 （p75TR）, in rats with cerebral ischemic stroke （CIS）, with the aim of exploring the possible mechanism of tonifying liver and kidney-essence herbs in recovery following in- jury to the central nervous system. METHODS： A cerebral ischemic stroke model in SD rats was established with the suture-occlusion method. Successful model rats were divided into placebo and herb groups at random; sham-operat- ed and control groups were set up simultaneously.Each of these groups was divided into six sub- groups at random. Expression of Nogo-A and p75TR was evaluated with immunofluorescence microsco- py at days 3, and weeks1, 2, 3, 4 and 8 after adminis- tration. RESULTS： Tonifying liver and kidney-essence herbs suppressed the expression of Nogo-A and p75T （P〈0.05 and P〈0.01, respectively）. CONCLUSION： Suppressing the expression of No- go-A and p75NTR is possibly one of the mechanisms underlying the ability of tonifying liver and kid- ney-essence herbs to promote recovery of the in- jured central nervous system.
基金National Natural Science Foundation of China(Grant No.81373973,81573872,81873228)Science and Technology Planning Project of Guangdong Province(Grant No.2017KZDXM018).
文摘To investigate the pharmacokinetics of effective components of Bu Yang Huang Wu Decoction(BYHWD)with different dosages of Astragalus(Yiqi groups and Huoxue groups)applicating in rats with middle cerebral artery occlusion(MCAO).Replicating the animal model of cerebral ischemia-reperfusion in rats,establishing the liquid-mass spectrometry method for the determination of BYHWD and researching the pharmacokinetics of effective components of yiqi groups of BYHWD with different dosages of astragalus(3.09,6.17,12.34 g/Kg)and Huoxue goups(2.32 g/Kg)when applicated seperately in the rats suffering from cerebral ischemia reperfusion injury after femoral vein administration.The pharmacokinetics of formononetin and paeoniflorin in the different dosage groups of BYHWD met the one-compartment model,and the t1/2 of formononetin and paeoniflorin in the low-dose Yiqi and Huoxue groups were(88.43±3.82,69.18±0.11)min,MRT were(138.56±4.83,113.62±2.42)min,and AUC0-twere(28488.35±4800.32,140614.80±23954.05)ng/mL min;The t1/2 of formononetin and paeoniflorin in the middle-dose Yiqi group and Huoxue group were(82.16±1.78,67.08±3.69)min,and MRT were(127.95±2.70,116.58±4.13),AUC0-t were(48619.25±6745.75,159026.00±15003.33)ng/mL min;The t1/2 of formononetin and paeoniflorin in the high-dose Yiqi and Huoxue groups were(80.29±1.12,69.69±0.87)min and MRT was(128.79±1.46,118.78±4.56)min AUC0-twere(109942.90±13101.83,189417.90±22311.00)ng/mL·min.The concentration rate of formononetin t1/2 brain was decreased with increase of Astragalus dose.However,no significant difference between these two variables was found during experiments.Furthermore,the experiments showed that the increasing dose of astragalus would affect the pharmacokinetic behavior of paeoniflorin in the Huoxue groups.More specifically,the result showed that paeoniflorin can be metabolized more slowly in the body when applicated in high dose of the jaundice administration groups.In this way,the effect of paeoniflorin can be lasted for longer time in the body and brain.
