Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng...Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber） drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immu- nofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regtflated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-[3 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-~ 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance depo- sition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra.展开更多
This study explored protective effects of Houshiheisan and its compound prescription of wind-dispelling drugs and deficiency-nourishing drugs on cerebral ischemia in terms of astrocyte activation and inflammatory fact...This study explored protective effects of Houshiheisan and its compound prescription of wind-dispelling drugs and deficiency-nourishing drugs on cerebral ischemia in terms of astrocyte activation and inflammatory factor expression.Results suggested that Houshiheisan lessened neuronal degeneration in the corpus striatum on the ischemic side of rats following cerebral ischemia/reperfusion injury,contributed to astrocyte activation and glial fibrillary acidic protein expression in the corpus striatum and decreased the levels of interleukin-2,interleukin-6, interleukin-1βand tumor necrosis factor-α.Factor analysis results demonstrated that deficiency-nourishing drugs were more beneficial in protecting neurons and upregulating glial fibrillary acidic protein expression than wind-dispelling drugs.However,wind-dispelling drugs were more effective in increasing the number of glial fibrillary acidic protein-positive cells and reducing inflammatory factor expression than deficiency-nourishing drugs.These indicate that different ingredients of Houshiheisan suppress cerebral ischemic injury by promoting astrocyte activation and diminishing inflammatory factor expression.展开更多
Houshiheisan,a classic prescription in traditional Chinese medicine,contains Flos Chrysanthemi,Radix Saposhnikoviae,Ramulus Cinnamomi,Rhizoma Chuanxiong,Radix et Rhizoma Asari,Radix Platycodonis,Rhizoma Atractylodis m...Houshiheisan,a classic prescription in traditional Chinese medicine,contains Flos Chrysanthemi,Radix Saposhnikoviae,Ramulus Cinnamomi,Rhizoma Chuanxiong,Radix et Rhizoma Asari,Radix Platycodonis,Rhizoma Atractylodis macrocephalae,Poria,Rhizoma Zingiberis,Radix Angelicae sinensis,Radix et Rhizoma Ginseng,Radix Scutellariae and Concha Ostreae.According to traditional Chinese medicine theory,Flos Chrysanthemi,Radix Saposhnikoviae,Ramulus Cinnamomi,Rhizoma Chuanxiong,Radix et Rhizoma Asari and Radix Platycodonis are wind-dispelling drugs;Rhizoma Atractylodis macrocephalae,Poria,Rhizoma Zingiberis,Radix Angelicae sinensis and Radix et Rhizoma Ginseng are deficiency-nourishing drugs.A large number of randomized controlled trials have shown that Houshiheisan is effective in treating stroke,but its mechanism of action is unknown.Axonal remodeling is an important mechanism in neural protection and regeneration.Therefore,this study explored the effect and mechanism of action of Houshiheisan on the repair of axons after cerebral ischemia.Rat models of focal cerebral ischemia were established by ligating the right middle cerebral artery.At 6 hours after model establishment,rats were intragastrically administered 10.5 g/kg Houshiheisan or 7.7 g/kg wind-dispelling drug or 2.59 g/kg deficiency-nourishing drug.These medicines were intragastrically administered as above every 24 hours for 7 consecutive days.Houshiheisan,and its wind-dispelling and deficiency-nourishing components reduced the neurological deficit score and ameliorated axon and neuron lesions after cerebral ischemia.Furthermore,Houshiheisan,and its wind-dispelling and deficiency-nourishing components decreased the expression of proteins that inhibit axonal remodeling：amyloid precursor protein,neurite outgrowth inhibitor protein A（Nogo-A）,Rho family small GTPase A（Rho A） and Rho-associated kinase 2（Rock2）,and increased the expression of growth associated protein-43,microtubule-associated protein-2,netrin-1,Ras-related C3 botulinum toxin substrate 1（Rac1） and cell division cycle 42（Cdc42）.The effect of Houshiheisan was stronger than wind-dispelling drugs or deficiency-nourishing drugs alone.In conclusion,Houshiheisan,and wind-dispelling and deficiency-nourishing drugs promote the repair of axons and nerve regeneration after cerebral ischemia through Nogo-A/Rho A/Rock2 and Netrin-1/Rac1/Cdc42 signaling pathways.These effects are strongest with Houshiheisan.展开更多
基金supported by the National Natural Science Foundation of China,No.30973782,81373526the Natural Science Foundation of Beijing,No.7102014,7122018the Beijing Municipal Higher Learning Institution Talent Teaching Plan"Young and Middle-aged Talented People Training"Project,No.PXM2011014226
文摘Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber） drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immu- nofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regtflated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-[3 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-~ 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance depo- sition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra.
基金funded by the National Natural Science Foundation of China,No.30973782the Natural Science Foundation of Beijing,No.7102014+1 种基金the Science and Technology Program of Chinese Medicine of Beijing City,No.JJ2008-042the Chinese Medicine Nursing Special Foundationof Beijing Education Commission,No.10ZYH04
文摘This study explored protective effects of Houshiheisan and its compound prescription of wind-dispelling drugs and deficiency-nourishing drugs on cerebral ischemia in terms of astrocyte activation and inflammatory factor expression.Results suggested that Houshiheisan lessened neuronal degeneration in the corpus striatum on the ischemic side of rats following cerebral ischemia/reperfusion injury,contributed to astrocyte activation and glial fibrillary acidic protein expression in the corpus striatum and decreased the levels of interleukin-2,interleukin-6, interleukin-1βand tumor necrosis factor-α.Factor analysis results demonstrated that deficiency-nourishing drugs were more beneficial in protecting neurons and upregulating glial fibrillary acidic protein expression than wind-dispelling drugs.However,wind-dispelling drugs were more effective in increasing the number of glial fibrillary acidic protein-positive cells and reducing inflammatory factor expression than deficiency-nourishing drugs.These indicate that different ingredients of Houshiheisan suppress cerebral ischemic injury by promoting astrocyte activation and diminishing inflammatory factor expression.
基金supported by the National Natural Science Foundation of China,No.81373526
文摘Houshiheisan,a classic prescription in traditional Chinese medicine,contains Flos Chrysanthemi,Radix Saposhnikoviae,Ramulus Cinnamomi,Rhizoma Chuanxiong,Radix et Rhizoma Asari,Radix Platycodonis,Rhizoma Atractylodis macrocephalae,Poria,Rhizoma Zingiberis,Radix Angelicae sinensis,Radix et Rhizoma Ginseng,Radix Scutellariae and Concha Ostreae.According to traditional Chinese medicine theory,Flos Chrysanthemi,Radix Saposhnikoviae,Ramulus Cinnamomi,Rhizoma Chuanxiong,Radix et Rhizoma Asari and Radix Platycodonis are wind-dispelling drugs;Rhizoma Atractylodis macrocephalae,Poria,Rhizoma Zingiberis,Radix Angelicae sinensis and Radix et Rhizoma Ginseng are deficiency-nourishing drugs.A large number of randomized controlled trials have shown that Houshiheisan is effective in treating stroke,but its mechanism of action is unknown.Axonal remodeling is an important mechanism in neural protection and regeneration.Therefore,this study explored the effect and mechanism of action of Houshiheisan on the repair of axons after cerebral ischemia.Rat models of focal cerebral ischemia were established by ligating the right middle cerebral artery.At 6 hours after model establishment,rats were intragastrically administered 10.5 g/kg Houshiheisan or 7.7 g/kg wind-dispelling drug or 2.59 g/kg deficiency-nourishing drug.These medicines were intragastrically administered as above every 24 hours for 7 consecutive days.Houshiheisan,and its wind-dispelling and deficiency-nourishing components reduced the neurological deficit score and ameliorated axon and neuron lesions after cerebral ischemia.Furthermore,Houshiheisan,and its wind-dispelling and deficiency-nourishing components decreased the expression of proteins that inhibit axonal remodeling：amyloid precursor protein,neurite outgrowth inhibitor protein A（Nogo-A）,Rho family small GTPase A（Rho A） and Rho-associated kinase 2（Rock2）,and increased the expression of growth associated protein-43,microtubule-associated protein-2,netrin-1,Ras-related C3 botulinum toxin substrate 1（Rac1） and cell division cycle 42（Cdc42）.The effect of Houshiheisan was stronger than wind-dispelling drugs or deficiency-nourishing drugs alone.In conclusion,Houshiheisan,and wind-dispelling and deficiency-nourishing drugs promote the repair of axons and nerve regeneration after cerebral ischemia through Nogo-A/Rho A/Rock2 and Netrin-1/Rac1/Cdc42 signaling pathways.These effects are strongest with Houshiheisan.
