Volume 16, Issue 8 (November 2022)
Qom Univ Med Sci J 2022, 16(8): 640-653 |
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Ethics code: IR.Shahed.REC.1396.15
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Jafari A, Joneidi E, Roghani M. The Protective Effect of Berberine Against Memory Impairment Induced by Intrahippocampal Injection of Aluminium Chloride in Rats. Qom Univ Med Sci J 2022; 16 (8) :640-653
URL: http://journal.muq.ac.ir/article-1-3443-en.html
URL: http://journal.muq.ac.ir/article-1-3443-en.html
1- Department of Medicine, School of Medicine, Shahed University, Tehran, Iran
2- Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran
3- Neurophysiology Research Center, Shahed University, Tehran, Iran ,mehjour@yahoo.com
2- Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran
3- Neurophysiology Research Center, Shahed University, Tehran, Iran ,
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The number of patients with cognitive impairments is expected to increase in the future. Alzheimer’s disease is the most common cognitive disorder characterized by debilitating memory deficit which imposes a considerable financial burden on the health systems. The main causes of Alzheimer’s disease are oxidative stress, energy imbalance, mitochondrial dysfunction, and neuroinflammation. Currently, symptomatic treatments are used to manage cognitive deficits in humans by targeting cholinergic or glutamatergic transmission. However, such symptomatic agents have shown improper efficacy. It is important to find new agents that can delay the onset and retard the progression of Alzheimer’s disease.
Aluminum is a neurotoxic agent that causes several neurodegenerative diseases such as Alzheimer’s disease. Exposure to Aluminum in rodents activates pathologic mechanisms which lead to cognitive impairment. Following its deposition in the brain tissue, mitochondrial dysfunction, oxidative stress, inflammation and apoptosis are observed. Berberine is an isoquinoline alkaloid that is found in some medicinal plants like berberis lycium with antioxidant, anti-inflammatory, hypoglycemic and anti-hyperglycemic properties and can reduce blood sugar level and inhibit acetylcholinesterase enzyme activity. In addition, berberine can ameliorate memory dysfunction and spatial learning and memory impairment in different conditions. The present study aims to investigate the effect of berberine on aluminum-induced memory impairment.
Methods
In this experimental study, 32 male rats weighing 180-230 g were randomly divided into four groups: Sham, berberine-treated sham, lesion, and berberine-treated lesion. To induce neurotoxicity, the animals were deeply anesthetized with intraperitoneal injection of ketamine (100 mg/kg) and xylazine (20 mg/kg) and then were placed in the stereotaxic device. In the lesion group, 5 µL of aluminum chloride (AlCl3) solution dissolved in normal saline was injected at a dose of 0.37 mg/kg into the left side of dorsal hippocampus. In the berberine-treated groups, the rats received 100 mg/kg of berberine daily from one hour before surgery up to one week after surgery in oral form. In the fourth week, all groups were tested for learning and memory using the shuttle box and passive avoidance test. During the retention and recall in this test, the step-through latency was measured. At the end, the levels of malondialdehyde (MDA) as a lipid peroxidation marker, reactive oxygen species (ROS) as a oxidative stress marker, and acetylcholinesterase (AChE) enzyme as an indicator of cholinergic function were measured using specific biochemical methods. In addition, protein level in the samples was measured by the Bradford assay. The data were described using Mean and standard error of the mean, and analyzed using one-way ANOVA and Tukey’s test to examine the differences between the study groups.
Results
There was no significant difference between the groups regarding initial latency in the passive avoidance test, but the step-through latency as an indicator of retention and recall ability in this test, was significantly lower in the lesion group compared to the sham group. Berberine administration was able to significantly increase this latency. In the berberine-treated sham group, no significant changes in this latency were observed compared to the sham group. Hippocampal MDA and ROS level in addition to the activity of AChE in the lesion group were significantly greater compared to the sham group. Berberine administration to the lesion group significantly reduced MDA, ROS, and AChE activity. In the berberine-treated sham group, no significant changes in the MDA, ROS, and AChE activity were reported.
Discussion
Administration 100 mg/kg berberine can improve memory and reduce the MDA, ROS, and AchE levels in rates with AlCl3 exposure. These effects can be due to decreased oxidative stress and improved cholinergic function.
Ethical Considerations
Compliance with ethical guidelines
All animal procedures of this study were conducted in accordance to ethical guidelines of Iranian Ministry of Health and Shahed University (no. IR.Shahed.REC.1396.15).
Funding
This research study was financially supported by Shahed University for MD thesis project of Atefeh Jafari.
Authors contributions
Conducted experiments, helped in data analysis and assisted in writing the initial draft of the paper: Atefeh Jafari; Helped in data analysis and paper writing: Ensiyeh Joneidi; designed the study, supervised the experiments and analyzed data: Mehrdad Roghani; All authors read and approved the final manuscript.
Conflicts of interest
The authors declared no conflict of interest.
Aluminum is a neurotoxic agent that causes several neurodegenerative diseases such as Alzheimer’s disease. Exposure to Aluminum in rodents activates pathologic mechanisms which lead to cognitive impairment. Following its deposition in the brain tissue, mitochondrial dysfunction, oxidative stress, inflammation and apoptosis are observed. Berberine is an isoquinoline alkaloid that is found in some medicinal plants like berberis lycium with antioxidant, anti-inflammatory, hypoglycemic and anti-hyperglycemic properties and can reduce blood sugar level and inhibit acetylcholinesterase enzyme activity. In addition, berberine can ameliorate memory dysfunction and spatial learning and memory impairment in different conditions. The present study aims to investigate the effect of berberine on aluminum-induced memory impairment.
Methods
In this experimental study, 32 male rats weighing 180-230 g were randomly divided into four groups: Sham, berberine-treated sham, lesion, and berberine-treated lesion. To induce neurotoxicity, the animals were deeply anesthetized with intraperitoneal injection of ketamine (100 mg/kg) and xylazine (20 mg/kg) and then were placed in the stereotaxic device. In the lesion group, 5 µL of aluminum chloride (AlCl3) solution dissolved in normal saline was injected at a dose of 0.37 mg/kg into the left side of dorsal hippocampus. In the berberine-treated groups, the rats received 100 mg/kg of berberine daily from one hour before surgery up to one week after surgery in oral form. In the fourth week, all groups were tested for learning and memory using the shuttle box and passive avoidance test. During the retention and recall in this test, the step-through latency was measured. At the end, the levels of malondialdehyde (MDA) as a lipid peroxidation marker, reactive oxygen species (ROS) as a oxidative stress marker, and acetylcholinesterase (AChE) enzyme as an indicator of cholinergic function were measured using specific biochemical methods. In addition, protein level in the samples was measured by the Bradford assay. The data were described using Mean and standard error of the mean, and analyzed using one-way ANOVA and Tukey’s test to examine the differences between the study groups.
Results
There was no significant difference between the groups regarding initial latency in the passive avoidance test, but the step-through latency as an indicator of retention and recall ability in this test, was significantly lower in the lesion group compared to the sham group. Berberine administration was able to significantly increase this latency. In the berberine-treated sham group, no significant changes in this latency were observed compared to the sham group. Hippocampal MDA and ROS level in addition to the activity of AChE in the lesion group were significantly greater compared to the sham group. Berberine administration to the lesion group significantly reduced MDA, ROS, and AChE activity. In the berberine-treated sham group, no significant changes in the MDA, ROS, and AChE activity were reported.
Discussion
Administration 100 mg/kg berberine can improve memory and reduce the MDA, ROS, and AchE levels in rates with AlCl3 exposure. These effects can be due to decreased oxidative stress and improved cholinergic function.
Ethical Considerations
Compliance with ethical guidelines
All animal procedures of this study were conducted in accordance to ethical guidelines of Iranian Ministry of Health and Shahed University (no. IR.Shahed.REC.1396.15).
Funding
This research study was financially supported by Shahed University for MD thesis project of Atefeh Jafari.
Authors contributions
Conducted experiments, helped in data analysis and assisted in writing the initial draft of the paper: Atefeh Jafari; Helped in data analysis and paper writing: Ensiyeh Joneidi; designed the study, supervised the experiments and analyzed data: Mehrdad Roghani; All authors read and approved the final manuscript.
Conflicts of interest
The authors declared no conflict of interest.
Type of Study: Original Article |
Subject:
فیزیولوژی
Received: 2022/04/12 | Accepted: 2022/10/4 | Published: 2022/11/1
Received: 2022/04/12 | Accepted: 2022/10/4 | Published: 2022/11/1
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