- Email: [email protected]
NEUROPROTECTIVE EFFECT OF CATHECINS GAMBIER
Poster Presentations: Sunday, July 16, 2017
P1-085
TETRAHYDROXYSTILBENE GLUCOSIDE AMELIORATES MEMORY AND MOVEMENT FUNCTIONS, PROTECTS SYNAPSES AND INHIBITS a-SYNUCLEIN AGGREGATION IN HIPPOCAMPUS AND STRIATUM IN AGED MICE
Lin Li, Fang-ling Sun, Cong Shen, Lan Zhang, Xuanwu Hospital of Capital Medical University, Beijing, China. Contact e-mail: [email protected] Background: Aging is the greatest risk factor of senile neurode-
generative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and dementia of Lewy body (DLB). Synaptic dysfunction plays an important role in the progression of cognitive impairment and movement disorder among these neurodegenerative diseases. Synaptic degeneration occurs early in the progression of AD involving neocortical and limbic system circuitries. Accumulating oligomeric a-synuclein may mediate early synaptic pathology in PD and DLB by disrupting synaptic vesicles. Polygonum multiflorum has been widely used in China as an anti-aging agent since ancient times. 2,3,5,4’Tetrahydroxystilbene-2-O-b-D-glucoside (TSG) is one of the main active component extracted from the root of Polygonum multiflorum. The purpose of this study was to investigate the effects of TSG on the memory and movement functions and its mechanisms related to synapses and a-synuclein in aged mice. Methods: The memory ability of mice was detected by step-through passive avoidance task. The movement function was measured by the pole test and rotarod test. Transmission electron microscopy was used to observe the synaptic ultrastructure. Western blotting was applied to measure the expression of synapse-related proteins and a-synuclein. Results: Intragastrical administration of TSG for 3 months significantly improved the memory and movement functions in aged mice. TSG treatment obviously protected the synaptic ultrastructure and increased the number of synaptic connections in the hippocampal CA1 region and striatum; enhanced the expression of synaptophysin, phosphorylated synapsin I and postsynaptic density protein 95 (PSD-95), elevated phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMK II) expression, and inhibited the overexpression and aggregation of a-synuclein in the hippocampus, striatum and cerebral cortex of aged mice. Conclusions: TSG improved the memory and movement functions in aged mice through protecting synapses and inhibiting a-synuclein overexpression and aggregation in multiple brain regions. The results suggest that TSG may have the potential to treat Alzheimer’s disease, Parkinson’s disease dementia and dementia of Lewy body.
P1-086
NEUROPROTECTIVE EFFECT OF CATHECINS GAMBIER
Linda Rosalina, Padang State University, Padang, Indonesia; Andalas University, Padang, Indonesia. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is an important social and economic issue for our societies. Patient with AD progress from stage of mild memory impairment to complete dementia. The development of therapeutic against this severe dementia requires assessing the effects of new drugs in animal model. Cathecin from Uncaria Gambier Indonesian traditional herbs
P271
have been found to possess anti-inflammatory and antioxidative effect. There was no report about Neuro protective effect of Cathecins gambier in Dawley Sprague as model of Alzheimer’s. In the present study, we investigated the neuroprotective effect of Cathecin Gambier on Beta Amyloid-42 plasma (Ab-42) and cognitive function of the Dawley Sprague as animal model for Alzheimer’s. Methods: Five groups of each 5 females, 12 weeks, Dawley Sprague, based on negative control, positive control, Cathechins dose 1, 2, 3. Four groups with ovarectomy and D-galctose 500mg/weight for 4 weeks. Four animals of each group underwent necropsy to collect the blood for blood evaluation on the second weeks after treatment of cathechins. Terminal sacrificed all groups in the 4th weeks after the treatment. Results: Rats treated Alzheimer showed shift to the light arms and spent long time compared with controls. It shows that the Alzheimer’s rat did not fear or panic, which is one of the characteristics amygdala damage. Since the amygdala also affect hypocampus memory’s performance. They
P272
Poster Presentations: Sunday, July 16, 2017
showed decreased the ability of spatial memory from the 2nd week of giving D-galactose and ovarectomy, but then they showed visible improvement of spatial memory in the 4th weeks. Trends of increasing in movement of group treated with high cathechins dose showed an improvement of locomotion. At the end of study, cathechins reduced the level of soluble beta amyloid 42 plasma. Low level of Ab is required to set up and maintain the plasticity of sinaps and to improve cognitive function. Conclusions: The result of the present study supports the concept of neuroprotective effect of Cathechin Gambier on Beta Amyloid plasma and cognitive function.
provide a new insight, for the treatment of AD and other tauopathies. P1-088
PROTECTIVE EFFECT OF CARVACROL AGAINST LIPOPOLYSACCHARIDEINDUCED NEUROINFLAMMATION, APOPTOSIS AND MEMORY DEFICIT IN MICE
Malvika Gursahani1, Nitin Gawali1, Sarayu Pai1, Aarti Anantram1, Renuka Munshi2, Mariam Degani1, Archana Juvekar1, 1Institute of Chemical Technology, Mumbai, India; 2TN Medical College & BYL Nair Hospital, Mumbai, India. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is a progressive neurode-
P1-087
MORINGA OLEIFERA (MO) ALLEVIATES HOMOCYSTEINE-INDUCED ALZHEIMER’S DISEASE-LIKE PATHOLOGY
Mahaman Yacoubou Abdoul Razak, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Contact e-mail: [email protected] Background: High level of homocysteine (Hcy) is a recognized
risk factor for Alzheimer’s Disease (AD) as suggested by many studies. Hcy increases brain Ab levels in APP transgenic mice, and Ab levels, tau phosphorylation and memory deficit in 3XTg AD mice. High Hcy also affects synaptic integrity and neuro-inflammation and induces oxidative stress through increase activation of NMDA receptors. Moringa Oleifera (MO) has been studied for its medicinal virtue. In AD, MO has been reported to have nootropic effect as well as antioxidative and anti-inflammatory effects. However, no effect of MO has been reported on Ab plaques and tau hyperphosphorylation. In the present study, we investigated the effect of MO on these 2 AD hallmarks and their underlying mechanisms. Methods: Adult male SD rates were injected with Hcy via vena caudalis and then treated with low or high dose intra gastric (IG) of MO before and/or after Hcy injection as preventive and curative treatment. After Hcy injection, the model group were given normal saline while the positive control SCR1693, IG. The control group were given normal saline. Memory, cognition and pathological changes were accessed. Results: MO not only prevent, but also rescued the cognitive impairment induced by Hcy treatment in SD rates. Moreover, MO increases SOD and decreases MDA levels in the treated animals. Interestingly MO prevents and decreases the Hyc induced tau hyperphosphorylation at different sites (S-396, S262, S-199, T-231, and T-404) in both hippocampus and cortex. MO also prevented and rescued neurodegeneration in the brain of rats. Hcy could increase NMDA receptors activation, then induce increase calcium influx and calpain activation which then could activate kinases such as GSk-3b or Cdk-5 thus increasing tau phosphorylation. We will therefore investigate this pathway and the possible involvement of MO in decreasing tau hyperphosphorylation. Conclusions: Here, for the first time, in the best of our knowledge, we provide evidence that MO could alleviate tau hyperphosphorylation induced by Hcy. Previous effects and this make MO a good candidate, and could
generative disorder. Its hallmarks include deposition of senile beta-amyloid plaques, neurofibrillary tangles, neuroinflammation and synaptic loss. In AD, neuroinflammation is not a passive system but instead contributes to the pathogenesis. Systemic lipopolysaccharide (LPS) is used to induce neuroinflammation and oxidative stress accompanied by an increase in the deposition of beta-amyloid in the brain. This leads to memory impairment and thus, the model was undertaken to evaluate the activity of carvacrol in a model of AD. Carvacrol exhibits acetylcholinesterase inhibitory (AChEi) activity in vitro. However, the effect on neuroinflammation induced memory impairment is unexplored. Methods: Carvacrol (5, 25 and 50 mg/ kg i.p.) was administered to Swiss albino mice for 14 days. Thereafter, they were dosed LPS (0.25mg/kg i.p) for 7 days along with carvacrol. Carvacrol treatment was continued for another 10 days and retention of memory was tested by Morris water Maze task (MWM) and Y maze memory test. At the end of the experiment, animals were sacrificed and the brain tissue homogenates were evaluated for antioxidant (lipid peroxidation and superoxide dismutase), anti-inflammatory (NF-kB), antiapoptotic (CASPASE-3), b-secretase and AChEi activities. Computational studies carried out involved molecular docking of carvacrol on AChE and b-secretaseand calculation of its binding energy. Results: Carvacrol dose dependently attenuated the deficits caused by LPS in MWM and Y maze memory test. The results obtained biochemically were consistent with those obtained in the behavioural tests. Lipid peroxidation, induced by LPS, was significantly mitigated by carvacrol whereas superoxide dismutase was significantly increased. LPS induced CASPASE-3 activation whereas carvacrol treatment prevented it. Significant AChEi activity was observed and b-secretase level was down regulated in the treatment groups. NF-kB, up-regulated by administration of LPS, was significantly attenuated by carvacrol treatment. Molecular docking studies indicated that carvacrol showed good interaction with AChE as well as b-secretase and the results of the computational work correlated well with their respective in vitro inhibitory activities. Conclusions: Carvacrol possesses significant antioxidant, anti-inflammatory and AChEi activity at preclinical stage and can be explored further for its potential use as prophylactic therapy in AD. P1-089
ORAL CURCUMIN IMPROVES PASSIVE AVOIDANCE MEMORY IN MALE MICE
Maryam Moosavi, Fatemeh Pirsalami, Leila Moezi, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran. Contact e-mail: [email protected]
P1-085
TETRAHYDROXYSTILBENE GLUCOSIDE AMELIORATES MEMORY AND MOVEMENT FUNCTIONS, PROTECTS SYNAPSES AND INHIBITS a-SYNUCLEIN AGGREGATION IN HIPPOCAMPUS AND STRIATUM IN AGED MICE
Lin Li, Fang-ling Sun, Cong Shen, Lan Zhang, Xuanwu Hospital of Capital Medical University, Beijing, China. Contact e-mail: [email protected] Background: Aging is the greatest risk factor of senile neurode-
generative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and dementia of Lewy body (DLB). Synaptic dysfunction plays an important role in the progression of cognitive impairment and movement disorder among these neurodegenerative diseases. Synaptic degeneration occurs early in the progression of AD involving neocortical and limbic system circuitries. Accumulating oligomeric a-synuclein may mediate early synaptic pathology in PD and DLB by disrupting synaptic vesicles. Polygonum multiflorum has been widely used in China as an anti-aging agent since ancient times. 2,3,5,4’Tetrahydroxystilbene-2-O-b-D-glucoside (TSG) is one of the main active component extracted from the root of Polygonum multiflorum. The purpose of this study was to investigate the effects of TSG on the memory and movement functions and its mechanisms related to synapses and a-synuclein in aged mice. Methods: The memory ability of mice was detected by step-through passive avoidance task. The movement function was measured by the pole test and rotarod test. Transmission electron microscopy was used to observe the synaptic ultrastructure. Western blotting was applied to measure the expression of synapse-related proteins and a-synuclein. Results: Intragastrical administration of TSG for 3 months significantly improved the memory and movement functions in aged mice. TSG treatment obviously protected the synaptic ultrastructure and increased the number of synaptic connections in the hippocampal CA1 region and striatum; enhanced the expression of synaptophysin, phosphorylated synapsin I and postsynaptic density protein 95 (PSD-95), elevated phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMK II) expression, and inhibited the overexpression and aggregation of a-synuclein in the hippocampus, striatum and cerebral cortex of aged mice. Conclusions: TSG improved the memory and movement functions in aged mice through protecting synapses and inhibiting a-synuclein overexpression and aggregation in multiple brain regions. The results suggest that TSG may have the potential to treat Alzheimer’s disease, Parkinson’s disease dementia and dementia of Lewy body.
P1-086
NEUROPROTECTIVE EFFECT OF CATHECINS GAMBIER
Linda Rosalina, Padang State University, Padang, Indonesia; Andalas University, Padang, Indonesia. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is an important social and economic issue for our societies. Patient with AD progress from stage of mild memory impairment to complete dementia. The development of therapeutic against this severe dementia requires assessing the effects of new drugs in animal model. Cathecin from Uncaria Gambier Indonesian traditional herbs
P271
have been found to possess anti-inflammatory and antioxidative effect. There was no report about Neuro protective effect of Cathecins gambier in Dawley Sprague as model of Alzheimer’s. In the present study, we investigated the neuroprotective effect of Cathecin Gambier on Beta Amyloid-42 plasma (Ab-42) and cognitive function of the Dawley Sprague as animal model for Alzheimer’s. Methods: Five groups of each 5 females, 12 weeks, Dawley Sprague, based on negative control, positive control, Cathechins dose 1, 2, 3. Four groups with ovarectomy and D-galctose 500mg/weight for 4 weeks. Four animals of each group underwent necropsy to collect the blood for blood evaluation on the second weeks after treatment of cathechins. Terminal sacrificed all groups in the 4th weeks after the treatment. Results: Rats treated Alzheimer showed shift to the light arms and spent long time compared with controls. It shows that the Alzheimer’s rat did not fear or panic, which is one of the characteristics amygdala damage. Since the amygdala also affect hypocampus memory’s performance. They
P272
Poster Presentations: Sunday, July 16, 2017
showed decreased the ability of spatial memory from the 2nd week of giving D-galactose and ovarectomy, but then they showed visible improvement of spatial memory in the 4th weeks. Trends of increasing in movement of group treated with high cathechins dose showed an improvement of locomotion. At the end of study, cathechins reduced the level of soluble beta amyloid 42 plasma. Low level of Ab is required to set up and maintain the plasticity of sinaps and to improve cognitive function. Conclusions: The result of the present study supports the concept of neuroprotective effect of Cathechin Gambier on Beta Amyloid plasma and cognitive function.
provide a new insight, for the treatment of AD and other tauopathies. P1-088
PROTECTIVE EFFECT OF CARVACROL AGAINST LIPOPOLYSACCHARIDEINDUCED NEUROINFLAMMATION, APOPTOSIS AND MEMORY DEFICIT IN MICE
Malvika Gursahani1, Nitin Gawali1, Sarayu Pai1, Aarti Anantram1, Renuka Munshi2, Mariam Degani1, Archana Juvekar1, 1Institute of Chemical Technology, Mumbai, India; 2TN Medical College & BYL Nair Hospital, Mumbai, India. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is a progressive neurode-
P1-087
MORINGA OLEIFERA (MO) ALLEVIATES HOMOCYSTEINE-INDUCED ALZHEIMER’S DISEASE-LIKE PATHOLOGY
Mahaman Yacoubou Abdoul Razak, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Contact e-mail: [email protected] Background: High level of homocysteine (Hcy) is a recognized
risk factor for Alzheimer’s Disease (AD) as suggested by many studies. Hcy increases brain Ab levels in APP transgenic mice, and Ab levels, tau phosphorylation and memory deficit in 3XTg AD mice. High Hcy also affects synaptic integrity and neuro-inflammation and induces oxidative stress through increase activation of NMDA receptors. Moringa Oleifera (MO) has been studied for its medicinal virtue. In AD, MO has been reported to have nootropic effect as well as antioxidative and anti-inflammatory effects. However, no effect of MO has been reported on Ab plaques and tau hyperphosphorylation. In the present study, we investigated the effect of MO on these 2 AD hallmarks and their underlying mechanisms. Methods: Adult male SD rates were injected with Hcy via vena caudalis and then treated with low or high dose intra gastric (IG) of MO before and/or after Hcy injection as preventive and curative treatment. After Hcy injection, the model group were given normal saline while the positive control SCR1693, IG. The control group were given normal saline. Memory, cognition and pathological changes were accessed. Results: MO not only prevent, but also rescued the cognitive impairment induced by Hcy treatment in SD rates. Moreover, MO increases SOD and decreases MDA levels in the treated animals. Interestingly MO prevents and decreases the Hyc induced tau hyperphosphorylation at different sites (S-396, S262, S-199, T-231, and T-404) in both hippocampus and cortex. MO also prevented and rescued neurodegeneration in the brain of rats. Hcy could increase NMDA receptors activation, then induce increase calcium influx and calpain activation which then could activate kinases such as GSk-3b or Cdk-5 thus increasing tau phosphorylation. We will therefore investigate this pathway and the possible involvement of MO in decreasing tau hyperphosphorylation. Conclusions: Here, for the first time, in the best of our knowledge, we provide evidence that MO could alleviate tau hyperphosphorylation induced by Hcy. Previous effects and this make MO a good candidate, and could
generative disorder. Its hallmarks include deposition of senile beta-amyloid plaques, neurofibrillary tangles, neuroinflammation and synaptic loss. In AD, neuroinflammation is not a passive system but instead contributes to the pathogenesis. Systemic lipopolysaccharide (LPS) is used to induce neuroinflammation and oxidative stress accompanied by an increase in the deposition of beta-amyloid in the brain. This leads to memory impairment and thus, the model was undertaken to evaluate the activity of carvacrol in a model of AD. Carvacrol exhibits acetylcholinesterase inhibitory (AChEi) activity in vitro. However, the effect on neuroinflammation induced memory impairment is unexplored. Methods: Carvacrol (5, 25 and 50 mg/ kg i.p.) was administered to Swiss albino mice for 14 days. Thereafter, they were dosed LPS (0.25mg/kg i.p) for 7 days along with carvacrol. Carvacrol treatment was continued for another 10 days and retention of memory was tested by Morris water Maze task (MWM) and Y maze memory test. At the end of the experiment, animals were sacrificed and the brain tissue homogenates were evaluated for antioxidant (lipid peroxidation and superoxide dismutase), anti-inflammatory (NF-kB), antiapoptotic (CASPASE-3), b-secretase and AChEi activities. Computational studies carried out involved molecular docking of carvacrol on AChE and b-secretaseand calculation of its binding energy. Results: Carvacrol dose dependently attenuated the deficits caused by LPS in MWM and Y maze memory test. The results obtained biochemically were consistent with those obtained in the behavioural tests. Lipid peroxidation, induced by LPS, was significantly mitigated by carvacrol whereas superoxide dismutase was significantly increased. LPS induced CASPASE-3 activation whereas carvacrol treatment prevented it. Significant AChEi activity was observed and b-secretase level was down regulated in the treatment groups. NF-kB, up-regulated by administration of LPS, was significantly attenuated by carvacrol treatment. Molecular docking studies indicated that carvacrol showed good interaction with AChE as well as b-secretase and the results of the computational work correlated well with their respective in vitro inhibitory activities. Conclusions: Carvacrol possesses significant antioxidant, anti-inflammatory and AChEi activity at preclinical stage and can be explored further for its potential use as prophylactic therapy in AD. P1-089
ORAL CURCUMIN IMPROVES PASSIVE AVOIDANCE MEMORY IN MALE MICE
Maryam Moosavi, Fatemeh Pirsalami, Leila Moezi, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran. Contact e-mail: [email protected]