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Research paper thumbnail of STUDIES OF MESPILUS GERMANICA LEAF FLAVONOIDS

Medlar (Mespilus germanica L.) from Rosaceae family is a spiny shrub with 2-3m height in wild and... more Medlar (Mespilus germanica L.) from Rosaceae family is a spiny shrub with 2-3m height in wild and 4-6 m when cultivated [1,2]. Medlar fruit and leaves are extremely rich sources of vitamin C and minerals (Potassium, Sodium, Calcium, Magnesium, Iron), antioxidants and flavonoids [2,3]. Many flavonoids are active principles of medicinal plants, exhibit pharmacological effects and contribute to human health [4]. Contents of sugars (fructose, glucose and sucrose), the main fatty acids (linoleic and palmitic acid), organic acids such as malic and citric acid, aspartate, glutamate and amino acids were determined in high levels in the mature medlar fruits [2]. Main flavonoid in Medlar leaf and fruit is Quercetin, maximum flavonoid content was recorded in their methanolic and aqueous extracts [1]. In this study leaf flavonoids of Mespilus germanica are reported using 2-dimentional paper (2-DPC) and thin layer chromatography (TLC). Results showed M. germanica leaf contain flavonoid sulphates, flavones C and C-/O glycosides. Aglycones was not found. Chrysin, Kaempferol, Myercetin, Quercetin and Rutin were found in the species leaf.

Research paper thumbnail of Diagnosis of the Hippocampal CA1 Pyramidal Neurons in STZ- Induced Alzheimer’s Rats

Alzheimer’s disease is one of the most prevalent brain neurodegenerative diseases with severe lea... more Alzheimer’s disease is one of the most prevalent brain neurodegenerative diseases with severe learning and memory defects that destruction of neurons in areas associated with cognitive functions (1).The hippocampus is made up of three areas: CA1, CA2 and CA3. The evolution of the disease the most prominent reduction of neuronal density especially was found in the CA1 and CA3 hippocampal areas (2). Alzheimer’s disease patients damage neurons involved in memory processing in different areas of the brain that seen such as the hippocampus (3). This study investigated the effect of ICV injection of streptozotocin (STZ) in memory retention and CA1 hippocampus neuronal density in male rats. This study investigated the effect of ICV injection of streptozotocin (STZ) in memory retention and CA1 hippocampus neuronaldensity in male rats.

Conference Presentations by matin ramezani

Research paper thumbnail of Effect of Medlar (Mespilus germanica L) fruit and seed flavonoids on learning and memory and also hippocampal CA3 neurons in Alzheimer's rats

Introduction: Alzheimer's disease is significantly developing and there is no decisive treatment ... more Introduction: Alzheimer's disease is significantly developing and there is no decisive treatment for that. So, it is urged to prevent in early stages. In present study, the effect of M.germanica fruit and seed flavonoids on learning and memory and hippocampal CA3 pyramidal neurons in Streptozotocin-induced Alzheimer's rats have been studied. Methods: M.germanica flavonids were extracted and identified by 2-Dimensional Paper Chromatography and Thin Layer Chromatography. Experimental groups including: 1. Control group, 2. STZ group, 3. STZ + 10 dose of M.germanica flavonoids group, and finally Pure flavonoids. STZ-i.c.v (10μl) in all groups except control group was injected at first and third days after surgery beside that, Intraperitoneal injection of flavonoids in all groups except control group, was performed everyday during the 21days. Control group received injection of saline. Afterwards was performed inhibitory avoidance test by shuttle box and immediately after that through perfusion, brains were separated to investigate hippocampal CA3 neurons. To inspect of behavioral data, we used SPSS (analysis one way ANOVA) and regarding the tissues data we used Prism. Results: M.germanica flavonoids in STZ+10mg/kg flavonoids group can restrict significantly deficiency in learning and memory and also improve neural damages in CA3 induced by STZ (p<0.001). Conclusion: Accordingly, it seems that M.germanica due to high levels of flavonoids provide useful efficacy on prevention of memorial loss and injury of neurons by STZ-icv and makes a potential in treatment of neurodegenerative diseases specially in Alzheimer's disease.

Research paper thumbnail of The effect of Mespilus germanica L. fruit flavonoids on average of intact neurons in hippocampal CA3 pyramidal Layer in Streptozotocine induced Alzheimer’s rats

Background: The fruit of this plant contain significant amount of flavonoids. Studies have shown ... more Background: The fruit of this plant contain significant amount of flavonoids. Studies have shown dietary sources of flavonoids may have positive effect on brain and reduces neuronal disorders such as Alzheimer's disease and Parkinson. Based on benefit functions of flavonoids to reduce oxidative stress and also decline free radicals generation and other useful properties. In this project examines Mespilus germanica L. flavonoids on average of intact neurons in hippocampal CA3 pyramidal layer in intracerebroventricular (icv) streptozotocine in male adult Wistar rats. According to development and importance of treatment the nervous system disorders such as Alzheimer's disease and due to lack of crucial treatment and also recommendations of traditional medicine, using plants to treat diseases, we investigated Mespilus germanica L. fruits flavonoids as a native plant in north region of Iran to treatment of Alzheimer’s disease. Methods: In this study, we used injection of stroptozotocin as a model of Alzheimer's disease in during a stereotaxic surgery. Therapeutic period was 21 days for all the rats. They were injected on the first and the third day by icv-STZ (3 mg/kg; bilateral with 10 μl volume on each side) or saline as a placebo (icv; bilateral with 10 μl volume on each side). Rats (n= 40) were randomly divided into 5 groups (n=8): 1. Sal-Sal, 2. STZ-Sal, 3. STZ- different flavonoids doses (5, 7.5, 10 mg/kg). In STZ + flavonoids groups, flavonoids was applied in doses of 5, 7.5 and 10 mg/kg, i.p., one day pre-surgery and every day in three weeks. After that rats were killed and perfused by Paraformaldehyde 4% then all brain sections were stained hematoxylin and eosin (H&E) to general morphology analysis and investigating average of intact neurons on hippocampal CA3 pyramidal layer in all the groups. The data were analyzed by prism software and one way ANOVA and T test. Analysis of cell count data were determined by Image J software. Results: We observed significant difference in morphology of neurons and compare average number of intact neurons in hippocampal CA3 pyramidal neurons between the control and streptozotocin (STZ) groups (P<0.001). Using three flavonoids of M. germanica fruit doses prevented damages results of icv-streptozotocine and improved the neurons and it was the reason of increasing the number of intact neurons in this Layer of hippocampus. The most impact was related to 10 mg/kg (P<0.001) and after the examination of its morphology, in addition to increasing the number of intact neurons we saw numerous mitotic divisions. The lowest effect in tissue processes was related to 5 mg/kg (p<0.05) and it was roughly equal to STZ group. Conclusion: The current study depict Flavonoids have beneficial effects in facilitate and improve the damage neurons through reduction of inflammatory cytokine levels and stimulate the neurogenesis and also neuronal survival and differentiation. It is due to antioxidant properties offlavonoids and also able to refuse damage cells in CA3 region and also in 10 mg/kg dose we can see the mitotic divisions in many neurons. Therefore seems Mespilus germanica L. due to high levels of flavonoids provide useful impact on preventing memorial loss caused by STZ-icv and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.

Papers by matin ramezani

Research paper thumbnail of A role for flavonoids in the prevention and/or treatment of cognitive dysfunction, learning, and memory deficits: a review of preclinical and clinical studies

Research paper thumbnail of Mespilus germanica Flavonoids Attenuate Cognitive Dysfunction in the Streptozotocin-induced Rat Model of Alzheimer's Disease

The current study illustrated the possible positive effects of flavonoids present in the leaves o... more The current study illustrated the possible positive effects of flavonoids present in the leaves of Mespilus germanica on cognitive performance, learning and memory function in an intra-cerebroventricular streptozotocin-induced Alzheimer’s disease model in male Wistar rats. Five groups (saline-saline control, streptozotocin-saline, and streptozotocin with different doses of flavonoids, 5, 10 and 20 mg/kg) of rats were examined. Rats received different doses of Mespilus germanica flavonoids or saline over three weeks starting one day before surgery. Next, they were assessed using a learning and memory test. After subjected to the behavioral test, the animals were perfused and their brains were fixed with paraformaldehyde 4 % and the tissue was further processed. Finally, the density of intact neurons in the hippocampal CA1 area in all groups was investigated. The results revealed that injection of streptozotocin significantly reduced cognitive function, memory retention as well as CA1 intact neurons compared to the control group. Flavonoids extracted by Mespilus germanica considerably eradicated the negative effects of streptozotocin. Accordingly, Mespilus germanica leaf flavonoids can improve cognitive deficits resulted from injection of streptozotocin.

Research paper thumbnail of Myricetin protects hippocampal CA3 pyramidal neurons and improves learning and memory impairments in rats with Alzheimer's disease

There is currently no treatment for effectively slowing the progression of Alzheimer's disease, s... more There is currently no treatment for effectively slowing the progression of Alzheimer's disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The present study investigated the effects of myricetin, a member of the flavonoids, on intracerebroventric-ular streptozotocin induced neuronal loss and memory impairment in rat models of Alzheimer's disease. Myricetin at 5 or 10 mg/kg was intraperitoneally injected into rats over 21 days. Control rats were treated with 10 mL/kg saline. Behavioral test (the shuttle box test) was performed on day 22 to examine learning and memory in rats. Immediately after that, hematoxylin-eosin staining was performed to observe the morphological change in hippocampal CA3 pyramidal neurons. Myricetin greatly increased the number of hippocampal CA3 pyramidal neurons and improved learning and memory impairments in rats with Alz-heimer's disease. These findings suggest that myricetin is beneficial for treatment of Alzheimer's disease.

Research paper thumbnail of Kaempferol promotes memory retention and density of hippocampal CA1 neurons in intra-cerebroventricular STZ-induced experimental AD model in Wistar rats

Background. Alzheimer's disease (AD) is a progressive degenerative disease which causes memory di... more Background. Alzheimer's disease (AD) is a progressive degenerative disease which causes memory disorders, decreases cognitive functions and abilities, and results in behavioural changes. Some studies have indicated that the flavonoids are able to cross the blood–brain barrier and have a positive effect on the reduction of neuronal damage disorders in the brain such as Alzheimer's disease. Materials and Methods. ICV administration of streptozotocin (3 mg/kg) was done on the first and the third day of the surgery and the animals' memory was evaluated through passive avoidance tasks. Animals were divided into five groups: Salin-Salin, STZ-Salin, and STZ-different kaempferol doses (5, 7/5, 10 mg/kg). All animals received different doses of kaempferol or saline for 3 weeks starting one day before the surgery. Later, they were put into a learning test. After the memory test, the animals were killed and their brains were fixed with Paraformaldehyde 4%, and tissue processing was done. Finally , density of intact neurons in the CA1 area of the hippocampus in the brains of all groups was investigated. Results. The ICV injections of STZ significantly reduced memory retention and intact pyramidal cells compared to the control group. The kaempferol improved the effects of STZ. Conclusion. Our findings show that kaempferol can optimize cognitive deficits caused by injections of STZ and also has some useful impacts on hippocampal CA1 pyramidal neurons.

Research paper thumbnail of STUDIES OF MESPILUS GERMANICA LEAF FLAVONOIDS

Medlar (Mespilus germanica L.) from Rosaceae family is a spiny shrub with 2-3m height in wild and... more Medlar (Mespilus germanica L.) from Rosaceae family is a spiny shrub with 2-3m height in wild and 4-6 m when cultivated [1,2]. Medlar fruit and leaves are extremely rich sources of vitamin C and minerals (Potassium, Sodium, Calcium, Magnesium, Iron), antioxidants and flavonoids [2,3]. Many flavonoids are active principles of medicinal plants, exhibit pharmacological effects and contribute to human health [4]. Contents of sugars (fructose, glucose and sucrose), the main fatty acids (linoleic and palmitic acid), organic acids such as malic and citric acid, aspartate, glutamate and amino acids were determined in high levels in the mature medlar fruits [2]. Main flavonoid in Medlar leaf and fruit is Quercetin, maximum flavonoid content was recorded in their methanolic and aqueous extracts [1]. In this study leaf flavonoids of Mespilus germanica are reported using 2-dimentional paper (2-DPC) and thin layer chromatography (TLC). Results showed M. germanica leaf contain flavonoid sulphates, flavones C and C-/O glycosides. Aglycones was not found. Chrysin, Kaempferol, Myercetin, Quercetin and Rutin were found in the species leaf.

Research paper thumbnail of Diagnosis of the Hippocampal CA1 Pyramidal Neurons in STZ- Induced Alzheimer’s Rats

Alzheimer’s disease is one of the most prevalent brain neurodegenerative diseases with severe lea... more Alzheimer’s disease is one of the most prevalent brain neurodegenerative diseases with severe learning and memory defects that destruction of neurons in areas associated with cognitive functions (1).The hippocampus is made up of three areas: CA1, CA2 and CA3. The evolution of the disease the most prominent reduction of neuronal density especially was found in the CA1 and CA3 hippocampal areas (2). Alzheimer’s disease patients damage neurons involved in memory processing in different areas of the brain that seen such as the hippocampus (3). This study investigated the effect of ICV injection of streptozotocin (STZ) in memory retention and CA1 hippocampus neuronal density in male rats. This study investigated the effect of ICV injection of streptozotocin (STZ) in memory retention and CA1 hippocampus neuronaldensity in male rats.

Research paper thumbnail of Effect of Medlar (Mespilus germanica L) fruit and seed flavonoids on learning and memory and also hippocampal CA3 neurons in Alzheimer's rats

Introduction: Alzheimer's disease is significantly developing and there is no decisive treatment ... more Introduction: Alzheimer's disease is significantly developing and there is no decisive treatment for that. So, it is urged to prevent in early stages. In present study, the effect of M.germanica fruit and seed flavonoids on learning and memory and hippocampal CA3 pyramidal neurons in Streptozotocin-induced Alzheimer's rats have been studied. Methods: M.germanica flavonids were extracted and identified by 2-Dimensional Paper Chromatography and Thin Layer Chromatography. Experimental groups including: 1. Control group, 2. STZ group, 3. STZ + 10 dose of M.germanica flavonoids group, and finally Pure flavonoids. STZ-i.c.v (10μl) in all groups except control group was injected at first and third days after surgery beside that, Intraperitoneal injection of flavonoids in all groups except control group, was performed everyday during the 21days. Control group received injection of saline. Afterwards was performed inhibitory avoidance test by shuttle box and immediately after that through perfusion, brains were separated to investigate hippocampal CA3 neurons. To inspect of behavioral data, we used SPSS (analysis one way ANOVA) and regarding the tissues data we used Prism. Results: M.germanica flavonoids in STZ+10mg/kg flavonoids group can restrict significantly deficiency in learning and memory and also improve neural damages in CA3 induced by STZ (p<0.001). Conclusion: Accordingly, it seems that M.germanica due to high levels of flavonoids provide useful efficacy on prevention of memorial loss and injury of neurons by STZ-icv and makes a potential in treatment of neurodegenerative diseases specially in Alzheimer's disease.

Research paper thumbnail of The effect of Mespilus germanica L. fruit flavonoids on average of intact neurons in hippocampal CA3 pyramidal Layer in Streptozotocine induced Alzheimer’s rats

Background: The fruit of this plant contain significant amount of flavonoids. Studies have shown ... more Background: The fruit of this plant contain significant amount of flavonoids. Studies have shown dietary sources of flavonoids may have positive effect on brain and reduces neuronal disorders such as Alzheimer's disease and Parkinson. Based on benefit functions of flavonoids to reduce oxidative stress and also decline free radicals generation and other useful properties. In this project examines Mespilus germanica L. flavonoids on average of intact neurons in hippocampal CA3 pyramidal layer in intracerebroventricular (icv) streptozotocine in male adult Wistar rats. According to development and importance of treatment the nervous system disorders such as Alzheimer's disease and due to lack of crucial treatment and also recommendations of traditional medicine, using plants to treat diseases, we investigated Mespilus germanica L. fruits flavonoids as a native plant in north region of Iran to treatment of Alzheimer’s disease. Methods: In this study, we used injection of stroptozotocin as a model of Alzheimer's disease in during a stereotaxic surgery. Therapeutic period was 21 days for all the rats. They were injected on the first and the third day by icv-STZ (3 mg/kg; bilateral with 10 μl volume on each side) or saline as a placebo (icv; bilateral with 10 μl volume on each side). Rats (n= 40) were randomly divided into 5 groups (n=8): 1. Sal-Sal, 2. STZ-Sal, 3. STZ- different flavonoids doses (5, 7.5, 10 mg/kg). In STZ + flavonoids groups, flavonoids was applied in doses of 5, 7.5 and 10 mg/kg, i.p., one day pre-surgery and every day in three weeks. After that rats were killed and perfused by Paraformaldehyde 4% then all brain sections were stained hematoxylin and eosin (H&E) to general morphology analysis and investigating average of intact neurons on hippocampal CA3 pyramidal layer in all the groups. The data were analyzed by prism software and one way ANOVA and T test. Analysis of cell count data were determined by Image J software. Results: We observed significant difference in morphology of neurons and compare average number of intact neurons in hippocampal CA3 pyramidal neurons between the control and streptozotocin (STZ) groups (P<0.001). Using three flavonoids of M. germanica fruit doses prevented damages results of icv-streptozotocine and improved the neurons and it was the reason of increasing the number of intact neurons in this Layer of hippocampus. The most impact was related to 10 mg/kg (P<0.001) and after the examination of its morphology, in addition to increasing the number of intact neurons we saw numerous mitotic divisions. The lowest effect in tissue processes was related to 5 mg/kg (p<0.05) and it was roughly equal to STZ group. Conclusion: The current study depict Flavonoids have beneficial effects in facilitate and improve the damage neurons through reduction of inflammatory cytokine levels and stimulate the neurogenesis and also neuronal survival and differentiation. It is due to antioxidant properties offlavonoids and also able to refuse damage cells in CA3 region and also in 10 mg/kg dose we can see the mitotic divisions in many neurons. Therefore seems Mespilus germanica L. due to high levels of flavonoids provide useful impact on preventing memorial loss caused by STZ-icv and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.

Research paper thumbnail of A role for flavonoids in the prevention and/or treatment of cognitive dysfunction, learning, and memory deficits: a review of preclinical and clinical studies

Research paper thumbnail of Mespilus germanica Flavonoids Attenuate Cognitive Dysfunction in the Streptozotocin-induced Rat Model of Alzheimer's Disease

The current study illustrated the possible positive effects of flavonoids present in the leaves o... more The current study illustrated the possible positive effects of flavonoids present in the leaves of Mespilus germanica on cognitive performance, learning and memory function in an intra-cerebroventricular streptozotocin-induced Alzheimer’s disease model in male Wistar rats. Five groups (saline-saline control, streptozotocin-saline, and streptozotocin with different doses of flavonoids, 5, 10 and 20 mg/kg) of rats were examined. Rats received different doses of Mespilus germanica flavonoids or saline over three weeks starting one day before surgery. Next, they were assessed using a learning and memory test. After subjected to the behavioral test, the animals were perfused and their brains were fixed with paraformaldehyde 4 % and the tissue was further processed. Finally, the density of intact neurons in the hippocampal CA1 area in all groups was investigated. The results revealed that injection of streptozotocin significantly reduced cognitive function, memory retention as well as CA1 intact neurons compared to the control group. Flavonoids extracted by Mespilus germanica considerably eradicated the negative effects of streptozotocin. Accordingly, Mespilus germanica leaf flavonoids can improve cognitive deficits resulted from injection of streptozotocin.

Research paper thumbnail of Myricetin protects hippocampal CA3 pyramidal neurons and improves learning and memory impairments in rats with Alzheimer's disease

There is currently no treatment for effectively slowing the progression of Alzheimer's disease, s... more There is currently no treatment for effectively slowing the progression of Alzheimer's disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The present study investigated the effects of myricetin, a member of the flavonoids, on intracerebroventric-ular streptozotocin induced neuronal loss and memory impairment in rat models of Alzheimer's disease. Myricetin at 5 or 10 mg/kg was intraperitoneally injected into rats over 21 days. Control rats were treated with 10 mL/kg saline. Behavioral test (the shuttle box test) was performed on day 22 to examine learning and memory in rats. Immediately after that, hematoxylin-eosin staining was performed to observe the morphological change in hippocampal CA3 pyramidal neurons. Myricetin greatly increased the number of hippocampal CA3 pyramidal neurons and improved learning and memory impairments in rats with Alz-heimer's disease. These findings suggest that myricetin is beneficial for treatment of Alzheimer's disease.

Research paper thumbnail of Kaempferol promotes memory retention and density of hippocampal CA1 neurons in intra-cerebroventricular STZ-induced experimental AD model in Wistar rats

Background. Alzheimer's disease (AD) is a progressive degenerative disease which causes memory di... more Background. Alzheimer's disease (AD) is a progressive degenerative disease which causes memory disorders, decreases cognitive functions and abilities, and results in behavioural changes. Some studies have indicated that the flavonoids are able to cross the blood–brain barrier and have a positive effect on the reduction of neuronal damage disorders in the brain such as Alzheimer's disease. Materials and Methods. ICV administration of streptozotocin (3 mg/kg) was done on the first and the third day of the surgery and the animals' memory was evaluated through passive avoidance tasks. Animals were divided into five groups: Salin-Salin, STZ-Salin, and STZ-different kaempferol doses (5, 7/5, 10 mg/kg). All animals received different doses of kaempferol or saline for 3 weeks starting one day before the surgery. Later, they were put into a learning test. After the memory test, the animals were killed and their brains were fixed with Paraformaldehyde 4%, and tissue processing was done. Finally , density of intact neurons in the CA1 area of the hippocampus in the brains of all groups was investigated. Results. The ICV injections of STZ significantly reduced memory retention and intact pyramidal cells compared to the control group. The kaempferol improved the effects of STZ. Conclusion. Our findings show that kaempferol can optimize cognitive deficits caused by injections of STZ and also has some useful impacts on hippocampal CA1 pyramidal neurons.