BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheime...BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer's disease. OBJECTIVE: Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein (App) and β -amyloid (A β ), to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 (SAMP8) and compare the effects with huperzine A. DESIGN, TIME AND SETTING: A completely randomized grouping design, controlled animal experiment was performed in the Center for Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS: Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups: PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. (batch No.: Z53021485, Yuxi, Yunan Province, China). Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. (batch No.: 20040801, Zhejiang, China). METHODS: The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES: After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency (time-to-platform), and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin (Syp) was tested by real time PCR and RT-PCR. RESULTS: The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group (P 〈 0.05). The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group (P 〈 0.05). CONCLUSION: These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer's disease. The therapeutic effects of PNS for Alzheimer's disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A.展开更多
With the intensification of the aging process of the world,Alzheimer's disease(AD),which is the main type of senile dementia,has become a primary problem in the present society.Lots of strategies have been used to...With the intensification of the aging process of the world,Alzheimer's disease(AD),which is the main type of senile dementia,has become a primary problem in the present society.Lots of strategies have been used to prevent and treat AD in animal nlodels and clinical trials,but most of them ended in failure.Panax notoginseng saponins(PNS)contain a variety of monomer compositions which have been separated and identified.Among of the monomer compositions,notoginseng saponin Rg1(Rg1)accounts for 20%of the cultivation of panax notoginseng roots.And now PNS have been reported to be widely used to treat cardicerebrovascular diseases and have neuroprotective effects to restrain theβ-amyloid peptide(Aβ)25-35-niediated apoptosis.Moreover,it is reported that PNS could accelerate the growth of nerve cells,increase the length of axons and promote synaptic plasticity.Whether Rg1 can ameliorate the cognitive impairment and the underlying mechanism has not been elucidated.To study the preventive effect of Rg1 on cognitive impairment and the possible mechanism,we established the cognitive impairment model in rats through Aβ1-42(2.6μg/μL,5μL)injection and then treated the rats with Rg1(25,50 and 100 mg/kg)administered intragastrically for 4 weeks.We observed that Aβ1-42 could induce spatial learning and memory deficits in rats.Simultaneously,Aβ1-42 injection also resulted in the reduced neuron number in comuammonis 1(CA1)and dentate gyrus(DG)of hippocampus,as well as the increased level of hyperphosphorylatedβ-amyloid precursor protein(APP)at Thr668 site with up-regulation ofβ-APP cleaving enzyme 1(BACE1)and presenilin 1(PS1)and down-regulation of a disintegrin and metalloprotease domain-containing protein 10(ADAM 10)and insulindegrading enzyme(IDE).Administration of Rg1 effectively rescued the cognitive impairment and neuronal loss,and inhibited theβ-secretase processing of APP through reducing APP-Thr668 phosphorylation and BACE1/PS1 expression,and increasing the expression of ADAM 10 and IDE.We concluded that Rg1 might have neuroprotective effects and could promote learning and memory ability,which might be a viable candidate in AD therapy probably through reducing the generation of Aβand increasing the degradation of Aβ.展开更多
Objective:Panax notoginseng saponins (PNS),extracted from rhizome of the herb Radix et Rhizoma Notoginseng (Panax notoginseng (Burk.) F.H.Chen),was recently discovered to have beneficial effects against neurological d...Objective:Panax notoginseng saponins (PNS),extracted from rhizome of the herb Radix et Rhizoma Notoginseng (Panax notoginseng (Burk.) F.H.Chen),was recently discovered to have beneficial effects against neurological damage.This study investigated the effects of PNS on cerebral ischemia and elucidated the molecular mechanisms underlying these effects.Methods:Middle cerebral artery occlusion rats were treated with PNS (3.6 mg/100 g or 7.2 mg/100 g per day) for 7 days,the gene of LINGO-1 was measured and the expression of protein synaptophysin,postsynaptic density protein 95,LINGO-1 and p-EGFR/p-PI3K/p-AKT were investigated.The weight and mNSS score of Sprague-Dawley rats in each group were recorded every day during the 7 days.Results:PNS promoted middle cerebral artery occlusion rats' weight and the recovery of neural function.PNS significantly decreased ischemia-induced LINGO-1 protein expression.PNS also elevated EGFR/PI3K/AKT phosphorylation levels.Conclusion:PNS promoted cerebral recovery from ischemic injury by accelerating synapse reconstruction and inhibiting the neuron growth negative regulatory protein LINGO-1 and activating the epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in vivo.展开更多
基金the National Natural Science Foundation of China, No: 30560189
文摘BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer's disease. OBJECTIVE: Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein (App) and β -amyloid (A β ), to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 (SAMP8) and compare the effects with huperzine A. DESIGN, TIME AND SETTING: A completely randomized grouping design, controlled animal experiment was performed in the Center for Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS: Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups: PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. (batch No.: Z53021485, Yuxi, Yunan Province, China). Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. (batch No.: 20040801, Zhejiang, China). METHODS: The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES: After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency (time-to-platform), and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin (Syp) was tested by real time PCR and RT-PCR. RESULTS: The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group (P 〈 0.05). The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group (P 〈 0.05). CONCLUSION: These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer's disease. The therapeutic effects of PNS for Alzheimer's disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A.
基金the National Natural Science Foundation of China(No.81673856,and No.81573865)Postdoctoral Science Foundation of China(No.2016M592319,and No.2017T100542)National Innovation and Entrepreneurship Training Program for College Students(No.201810507019).
文摘With the intensification of the aging process of the world,Alzheimer's disease(AD),which is the main type of senile dementia,has become a primary problem in the present society.Lots of strategies have been used to prevent and treat AD in animal nlodels and clinical trials,but most of them ended in failure.Panax notoginseng saponins(PNS)contain a variety of monomer compositions which have been separated and identified.Among of the monomer compositions,notoginseng saponin Rg1(Rg1)accounts for 20%of the cultivation of panax notoginseng roots.And now PNS have been reported to be widely used to treat cardicerebrovascular diseases and have neuroprotective effects to restrain theβ-amyloid peptide(Aβ)25-35-niediated apoptosis.Moreover,it is reported that PNS could accelerate the growth of nerve cells,increase the length of axons and promote synaptic plasticity.Whether Rg1 can ameliorate the cognitive impairment and the underlying mechanism has not been elucidated.To study the preventive effect of Rg1 on cognitive impairment and the possible mechanism,we established the cognitive impairment model in rats through Aβ1-42(2.6μg/μL,5μL)injection and then treated the rats with Rg1(25,50 and 100 mg/kg)administered intragastrically for 4 weeks.We observed that Aβ1-42 could induce spatial learning and memory deficits in rats.Simultaneously,Aβ1-42 injection also resulted in the reduced neuron number in comuammonis 1(CA1)and dentate gyrus(DG)of hippocampus,as well as the increased level of hyperphosphorylatedβ-amyloid precursor protein(APP)at Thr668 site with up-regulation ofβ-APP cleaving enzyme 1(BACE1)and presenilin 1(PS1)and down-regulation of a disintegrin and metalloprotease domain-containing protein 10(ADAM 10)and insulindegrading enzyme(IDE).Administration of Rg1 effectively rescued the cognitive impairment and neuronal loss,and inhibited theβ-secretase processing of APP through reducing APP-Thr668 phosphorylation and BACE1/PS1 expression,and increasing the expression of ADAM 10 and IDE.We concluded that Rg1 might have neuroprotective effects and could promote learning and memory ability,which might be a viable candidate in AD therapy probably through reducing the generation of Aβand increasing the degradation of Aβ.
基金funding from the National Natural Science Foundation of China(Grant Nos.81573926 and 81173235).
文摘Objective:Panax notoginseng saponins (PNS),extracted from rhizome of the herb Radix et Rhizoma Notoginseng (Panax notoginseng (Burk.) F.H.Chen),was recently discovered to have beneficial effects against neurological damage.This study investigated the effects of PNS on cerebral ischemia and elucidated the molecular mechanisms underlying these effects.Methods:Middle cerebral artery occlusion rats were treated with PNS (3.6 mg/100 g or 7.2 mg/100 g per day) for 7 days,the gene of LINGO-1 was measured and the expression of protein synaptophysin,postsynaptic density protein 95,LINGO-1 and p-EGFR/p-PI3K/p-AKT were investigated.The weight and mNSS score of Sprague-Dawley rats in each group were recorded every day during the 7 days.Results:PNS promoted middle cerebral artery occlusion rats' weight and the recovery of neural function.PNS significantly decreased ischemia-induced LINGO-1 protein expression.PNS also elevated EGFR/PI3K/AKT phosphorylation levels.Conclusion:PNS promoted cerebral recovery from ischemic injury by accelerating synapse reconstruction and inhibiting the neuron growth negative regulatory protein LINGO-1 and activating the epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in vivo.