BEE VENOM TREATMENT AND STUDIES FOR ALZHEIMERS
|
There are several people, who have a misconception that dementia is only linked with aging. But in reality, dementia has little to do with the natural process of aging. It is a debilitating, chronic and common disease. A subject of dementia is defined as someone: having a memory disorder accompanied by any sort of cognitive disorder. Difficulty to think or process certain languages or having impaired judgment is known as a cognitive disorder. There are three main groups termed as: secondary dementia, primary degenerative dementia, and vascular dementia disease.
Alzheimer's is one of the most common types of dementia disease that covers nearly 70% of the cases. While vascular dementia is the second most common type of dementia disease that covers nearly 20% of the overall cases. |
What happens in the patients of Alzheimer's is that; the nerve cells present in the brain start depleting and that leads to the general loss of memory. The abundance of protein cells in the brain causes this disease. Known as amyloid plaques, they are composed of fibrils – lengthy strands of beta-amyloid protein.
The scientific cause behind the depletion of neurons is still unclear, but it is confirmed that beta-amyloid is the type of protein that has some sort of involvement in this process. Other associated risk factors for the patients of Alzheimer's are heredity and old age. In several cases, it has been reported that repeated head injuries can also lead to Alzheimer’s.
Symptoms of Alzheimer’s disease
Like any other disease, Alzheimer’s has also different symptoms. Let’s have a look at how the patients find it difficult to manage their everyday tasks.
Bee Venom Phospholipase A2 Ameliorates Alzheimer’s Disease Pathology in Aβ Vaccination Treatment without Inducing Neuro-Inflammation in A 3xtg-AD Mouse Model (.pdf)
Alzheimer’s disease, as said, is one of the most common types of dementia. Describing it more clearly, it is characterized through an imbalance caused due to clearance and production of amyloid-beta and tau proteins. Vaccination available for amyloid-beta has certainly helped in reducing amyloid-beta pathology in various experimental AD mouse subjects.
An initial clinical trial conducted for an active amyloid-beta vaccine had to be halted due to the production of acute meningoencephalitis in nearly 6% of immunized patients. In this clinical study, the main aim was to determine if (bvPLA2) bee venom phospholipase A2 treatment, following a regular pattern, will induce ameliorate AD pathology and Tregs without the unwanted T-cell mediated irritation or not.
First of all, the effects of bee venom phospholipase on inflammatory intrusion caused by amyloid-beta vaccination were investigated carefully. The inflammatory combinations of CD3+T macrophages and lymphocytes found in the spinal cords and brains of mice were treated with amyloid-beta. It was noted that the administration of bee venom phospholipase dramatically helped in eliminating inflammation of the central nervous system following Aβ immunization.
Bee venom phospholipase administration in the AD model mice significantly enhanced the cognitive discrepancies and eventually reduced Aβ accumulation in brains of the AD model mice. Brain glucose metabolism was also examined by making use of positron emission tomography with the 18F-2fluoro-2-deoxy-D-glucose. The result showed that cerebral glucose concentration was higher in brains of Aβ administered AD model mice that also got bee venom phospholipase treatment than those that did not get this therapy.
In light of this study, it can be concluded that modulation of the Treg population through bee venom phospholipase treatment serves as a fresh therapeutic approach to contain the development of Alzheimer's in combination with Aβ vaccination. Also, no serious inflammatory responses were recorded.
Growing evidence indicates that the inflection of Treg function can serve as a potential therapeutic channel for the neuroprotection required in different neurodegenerative ailments. Therefore, a better understanding of the Tregs can finally facilitate the development of effective strategies that can further help modulate inflammatory responses involved in Alzheimer’s disease.
Neuroprotective Effects of Bee Venom Phospholipase A2 In The 3xtg AD Mouse Model Of Alzheimer’s disease
AD, also known as Alzheimer's disease is a chronic neuro-inflammatory disease. The CD4 (+) Foxp3 (+) Tregs (regulatory T cells) are responsible for modulating different inflammatory diseases by suppressing Th cell activation. To support this statement several pieces of evidence present indicate Tregs also play a beneficial role in different neurodegenerative diseases. It was also found that the overall population of Treg cells increased significantly after bee venom phospholipase A2 treatment in both: in vivo and in vitro.
To examine the therapeutic effects of bee venom phosphate A2, on subjects of Alzheimer's, bvPLA2 was given to AD model mice (3xTg-AD mice). Furthermore, the level of amyloid-beta deposits in the hippocampus, CD (+) 4 T cell infiltration, microglia activation, and glucose metabolism were analyzed carefully to examine the neuroprotective effects of bvPLA2.
It was derived that bee venom phospholipase A2 therapy helped in enhancing the cognitive functions of AD model mice and also increased the glucose metabolism. Assessment was done with the 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) positron emission tomography (PET) method. Also, the level of Aβ deposit in the hippocampus was significantly decreased after bee venom phospholipase A2 treatment.
To explain this neuroprotective effect of bee venom phospholipase A2, it can be said that it has a strong association with the reduction and microglial deactivation of CD4 (+) T cell infiltration. Furthermore, the neuroprotective effect of bee venom phospholipase A2 was abolished in the Treg depleted mice. The study done strongly suggests that an increase in the Treg population, due to bee venom phospholipase A2 therapy, can inhibit the development of Alzheimer's disease in AD model mice.
Bee Venom Ameliorates Lipopolysaccharide-Induced Memory Loss by Preventing NF-Kappab Pathway
Alzheimer's disease is a neurodegenerative disease that develops due to damage caused to neurons in the brain. Subjects of Alzheimer's lose their capability to learn new things and also face declarative and non-declarative memory issues. It has been found that Alzheimer's is directly related to the development of amyloid-beta peptides. They are produced from the APP (amyloid precursor protein). The amyloid precursor protein is disintegrated into soluble sAPPβ (amyloid precursor protein beta), C99 (carboxy-terminal 99 amino acid) and β secretase; BACE1 (protein by β site APP cleaving enzyme. In patients of Alzheimer's disease, it has been observed that they have a very high level of Aβ and accumulated Aβ.
LPS (Lipopolysaccharide) can influence amyloidogenesis and trigger neuroinflammation in the neuronal cells. Lipopolysaccharide activates the inflammatory cells like microglia and astrocytes in the brain that eventually result in the development of neuroinflammation. Lipopolysaccharide also results in a buildup of Aβ through an increased cleavage of the APP by aggregating γ-secretase and BACE1 activation. The nuclear factor kappaB can easily be activated by the LPS that eventually leads to the production of inflammatory genes like tumor necrosis factor-a, inducible nitric oxide synthase, and cyclooxygenase-2.
BV (Bee venom) has been used for a long time, in different parts of the world, as a traditional cure. Therapeutically, it is one of the best forms of natural treatments that have helped in dealing with severe symptoms of rheumatism, arthritis and even cancer. The reason is that bee venom has several active elements like peptides, enzymes, and biogenic amines. In the light of different researches done, it has been proved that bee venom possesses anti-inflammatory properties.
The entire research work was done in support of lent by the National Research Foundation of Korea. Funds were also provided by the government of Korea. For carrying out this clinical study, bee venom was obtained from the You-Miel Bee Venom Ltd. (Korea). Bee venom had the following composition: 50% melittin, 3% mast cell de-granulating peptide, 12% phospholipase A2, 1% lysophospholipase A, 1.5% histidine, 5% 6-pentyl a-pyrone lipids, 0.5% secarpin, 0.1% tertiapin, 0.1% procamine, 2% hyaluronidase, 3% amine, 5% carbohydrate, and 27% of others. It also included: unknown amino acids having 99.5% purity, norepinephrine, dopamine, phosphomonoesterase acid, invertase, glucosidase, and protease inhibitor. While melittin was obtained from Sigma-Aldrich (USA).
7 to 8-week old male mice were obtained from Daehan Biolink, Korea. They were handled according to the animal care instructions provided by the Korean FDA. It was also made sure that all of the experiments are carried out by the guidelines provided by the Guidelines for the Care and Use of Animals. Special efforts were carried out to make sure that the subject mice did not suffer during clinical trials and that only a minimum number of mice are used. All of the mice were kept in a special automatic temperature-controlled room having relative humidity levels and proper light to dark cycle. The temperature was maintained around 25 degrees centigrade, humidity around 50% and 12hours of light and 12 hours of dark.
To prepare the mice, LPS 2.5mg was given intraperitoneally. LPS was dissolved and the aliquots in purified water were stored at a freezing temperature of minus 20-degree centigrade. Divisions were made further into four different groups with each group having 8 mice.
First of all intraperitoneal injection of bee venom was given and after that i.p injection of control (saline) or LPS was given after a period of thirty minutes. The dosage of bee venom was maintained at the same level concerning the studies carried out earlier. This regime was adopted for a period of 7 days straight. After that time memory capacity and behavioral test of learning were both assessed through different tests – passive avoidance and water maze test.
Passive avoidance test is a simple method used for memory testing. Passive avoidance response was evaluated through a step-through device provided by Med Associates Inc, Vermont, USA. The device is a specially devised apparatus that consists of a dark and an illuminated compartment. Through both of these methods, the behavioral pattern of the subject AD mice was observed. The water maze test is one of the most widely used methods for carrying out a memory test. Special procedures are outlined by Morris et al for performing this test. Maze testing was fulfilled by the SMART-CS program and equipment (Barcelona, Spain). These tests were carried out on the first day, third day and the seventh day of the clinical experimentation.
It is confirmed that neuroinflammation and Aβ accumulation in the brain, leads to the development of Alzheimer's that eventually causes the death of neuronal cells. This study showed that bee venom helped in preventing LPS induced weakening of memory. Bee venom also helped in improving LPS mediated neuroinflammatory and amyloidogenesis reactions in the brain. Data gathered indicated that bee venom could be actively used to control symptoms of Alzheimer's disease.
The statistics and results obtained from this clinical study all clarified that bee venom, through its regular dosage and administration technique can help in controlling neuroinflammation and amyloidogenesis to an impressive extent. This derivation has been made according to the observation confirmed by the expressions of iNOS, COX2, IBA1, and GFAP. All of these proteins were brought down in the bee venom injection groups. Furthermore, it was found that bee venom has also a prominent effect on the reticence of NFκB activation. Bee venom can also be used as an effective treatment of neuroinflammation and amyloidogenesis diseases like Alzheimer’s and the disease by the NF kappa B activation.
The scientific cause behind the depletion of neurons is still unclear, but it is confirmed that beta-amyloid is the type of protein that has some sort of involvement in this process. Other associated risk factors for the patients of Alzheimer's are heredity and old age. In several cases, it has been reported that repeated head injuries can also lead to Alzheimer’s.
Symptoms of Alzheimer’s disease
Like any other disease, Alzheimer’s has also different symptoms. Let’s have a look at how the patients find it difficult to manage their everyday tasks.
- Alzheimer's leads to a short term memory loss. It becomes difficult for patients to remember whatever happened recently.
- A person suffering from Alzheimer's finds it problematic to express himself/herself. There is some difficulty faced while communicating verbally and that is due to inferior vocals. In the same manner, due to the improper response of different body parts, it results in poor coordination and movement.
- The period of staying focused becomes very low. So a patient of Alzheimer's cannot manage different daily tasks easily.
Bee Venom Phospholipase A2 Ameliorates Alzheimer’s Disease Pathology in Aβ Vaccination Treatment without Inducing Neuro-Inflammation in A 3xtg-AD Mouse Model (.pdf)
Alzheimer’s disease, as said, is one of the most common types of dementia. Describing it more clearly, it is characterized through an imbalance caused due to clearance and production of amyloid-beta and tau proteins. Vaccination available for amyloid-beta has certainly helped in reducing amyloid-beta pathology in various experimental AD mouse subjects.
An initial clinical trial conducted for an active amyloid-beta vaccine had to be halted due to the production of acute meningoencephalitis in nearly 6% of immunized patients. In this clinical study, the main aim was to determine if (bvPLA2) bee venom phospholipase A2 treatment, following a regular pattern, will induce ameliorate AD pathology and Tregs without the unwanted T-cell mediated irritation or not.
First of all, the effects of bee venom phospholipase on inflammatory intrusion caused by amyloid-beta vaccination were investigated carefully. The inflammatory combinations of CD3+T macrophages and lymphocytes found in the spinal cords and brains of mice were treated with amyloid-beta. It was noted that the administration of bee venom phospholipase dramatically helped in eliminating inflammation of the central nervous system following Aβ immunization.
Bee venom phospholipase administration in the AD model mice significantly enhanced the cognitive discrepancies and eventually reduced Aβ accumulation in brains of the AD model mice. Brain glucose metabolism was also examined by making use of positron emission tomography with the 18F-2fluoro-2-deoxy-D-glucose. The result showed that cerebral glucose concentration was higher in brains of Aβ administered AD model mice that also got bee venom phospholipase treatment than those that did not get this therapy.
In light of this study, it can be concluded that modulation of the Treg population through bee venom phospholipase treatment serves as a fresh therapeutic approach to contain the development of Alzheimer's in combination with Aβ vaccination. Also, no serious inflammatory responses were recorded.
Growing evidence indicates that the inflection of Treg function can serve as a potential therapeutic channel for the neuroprotection required in different neurodegenerative ailments. Therefore, a better understanding of the Tregs can finally facilitate the development of effective strategies that can further help modulate inflammatory responses involved in Alzheimer’s disease.
Neuroprotective Effects of Bee Venom Phospholipase A2 In The 3xtg AD Mouse Model Of Alzheimer’s disease
AD, also known as Alzheimer's disease is a chronic neuro-inflammatory disease. The CD4 (+) Foxp3 (+) Tregs (regulatory T cells) are responsible for modulating different inflammatory diseases by suppressing Th cell activation. To support this statement several pieces of evidence present indicate Tregs also play a beneficial role in different neurodegenerative diseases. It was also found that the overall population of Treg cells increased significantly after bee venom phospholipase A2 treatment in both: in vivo and in vitro.
To examine the therapeutic effects of bee venom phosphate A2, on subjects of Alzheimer's, bvPLA2 was given to AD model mice (3xTg-AD mice). Furthermore, the level of amyloid-beta deposits in the hippocampus, CD (+) 4 T cell infiltration, microglia activation, and glucose metabolism were analyzed carefully to examine the neuroprotective effects of bvPLA2.
It was derived that bee venom phospholipase A2 therapy helped in enhancing the cognitive functions of AD model mice and also increased the glucose metabolism. Assessment was done with the 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) positron emission tomography (PET) method. Also, the level of Aβ deposit in the hippocampus was significantly decreased after bee venom phospholipase A2 treatment.
To explain this neuroprotective effect of bee venom phospholipase A2, it can be said that it has a strong association with the reduction and microglial deactivation of CD4 (+) T cell infiltration. Furthermore, the neuroprotective effect of bee venom phospholipase A2 was abolished in the Treg depleted mice. The study done strongly suggests that an increase in the Treg population, due to bee venom phospholipase A2 therapy, can inhibit the development of Alzheimer's disease in AD model mice.
Bee Venom Ameliorates Lipopolysaccharide-Induced Memory Loss by Preventing NF-Kappab Pathway
Alzheimer's disease is a neurodegenerative disease that develops due to damage caused to neurons in the brain. Subjects of Alzheimer's lose their capability to learn new things and also face declarative and non-declarative memory issues. It has been found that Alzheimer's is directly related to the development of amyloid-beta peptides. They are produced from the APP (amyloid precursor protein). The amyloid precursor protein is disintegrated into soluble sAPPβ (amyloid precursor protein beta), C99 (carboxy-terminal 99 amino acid) and β secretase; BACE1 (protein by β site APP cleaving enzyme. In patients of Alzheimer's disease, it has been observed that they have a very high level of Aβ and accumulated Aβ.
LPS (Lipopolysaccharide) can influence amyloidogenesis and trigger neuroinflammation in the neuronal cells. Lipopolysaccharide activates the inflammatory cells like microglia and astrocytes in the brain that eventually result in the development of neuroinflammation. Lipopolysaccharide also results in a buildup of Aβ through an increased cleavage of the APP by aggregating γ-secretase and BACE1 activation. The nuclear factor kappaB can easily be activated by the LPS that eventually leads to the production of inflammatory genes like tumor necrosis factor-a, inducible nitric oxide synthase, and cyclooxygenase-2.
BV (Bee venom) has been used for a long time, in different parts of the world, as a traditional cure. Therapeutically, it is one of the best forms of natural treatments that have helped in dealing with severe symptoms of rheumatism, arthritis and even cancer. The reason is that bee venom has several active elements like peptides, enzymes, and biogenic amines. In the light of different researches done, it has been proved that bee venom possesses anti-inflammatory properties.
The entire research work was done in support of lent by the National Research Foundation of Korea. Funds were also provided by the government of Korea. For carrying out this clinical study, bee venom was obtained from the You-Miel Bee Venom Ltd. (Korea). Bee venom had the following composition: 50% melittin, 3% mast cell de-granulating peptide, 12% phospholipase A2, 1% lysophospholipase A, 1.5% histidine, 5% 6-pentyl a-pyrone lipids, 0.5% secarpin, 0.1% tertiapin, 0.1% procamine, 2% hyaluronidase, 3% amine, 5% carbohydrate, and 27% of others. It also included: unknown amino acids having 99.5% purity, norepinephrine, dopamine, phosphomonoesterase acid, invertase, glucosidase, and protease inhibitor. While melittin was obtained from Sigma-Aldrich (USA).
7 to 8-week old male mice were obtained from Daehan Biolink, Korea. They were handled according to the animal care instructions provided by the Korean FDA. It was also made sure that all of the experiments are carried out by the guidelines provided by the Guidelines for the Care and Use of Animals. Special efforts were carried out to make sure that the subject mice did not suffer during clinical trials and that only a minimum number of mice are used. All of the mice were kept in a special automatic temperature-controlled room having relative humidity levels and proper light to dark cycle. The temperature was maintained around 25 degrees centigrade, humidity around 50% and 12hours of light and 12 hours of dark.
To prepare the mice, LPS 2.5mg was given intraperitoneally. LPS was dissolved and the aliquots in purified water were stored at a freezing temperature of minus 20-degree centigrade. Divisions were made further into four different groups with each group having 8 mice.
- BV (1.6 μg/kg) + LPS group (BV 1.6)
- BV (0.8 μg/kg) + LPS group (BV 0.8)
- saline + LPS group (LPS)
- saline + saline group (control)
First of all intraperitoneal injection of bee venom was given and after that i.p injection of control (saline) or LPS was given after a period of thirty minutes. The dosage of bee venom was maintained at the same level concerning the studies carried out earlier. This regime was adopted for a period of 7 days straight. After that time memory capacity and behavioral test of learning were both assessed through different tests – passive avoidance and water maze test.
Passive avoidance test is a simple method used for memory testing. Passive avoidance response was evaluated through a step-through device provided by Med Associates Inc, Vermont, USA. The device is a specially devised apparatus that consists of a dark and an illuminated compartment. Through both of these methods, the behavioral pattern of the subject AD mice was observed. The water maze test is one of the most widely used methods for carrying out a memory test. Special procedures are outlined by Morris et al for performing this test. Maze testing was fulfilled by the SMART-CS program and equipment (Barcelona, Spain). These tests were carried out on the first day, third day and the seventh day of the clinical experimentation.
It is confirmed that neuroinflammation and Aβ accumulation in the brain, leads to the development of Alzheimer's that eventually causes the death of neuronal cells. This study showed that bee venom helped in preventing LPS induced weakening of memory. Bee venom also helped in improving LPS mediated neuroinflammatory and amyloidogenesis reactions in the brain. Data gathered indicated that bee venom could be actively used to control symptoms of Alzheimer's disease.
The statistics and results obtained from this clinical study all clarified that bee venom, through its regular dosage and administration technique can help in controlling neuroinflammation and amyloidogenesis to an impressive extent. This derivation has been made according to the observation confirmed by the expressions of iNOS, COX2, IBA1, and GFAP. All of these proteins were brought down in the bee venom injection groups. Furthermore, it was found that bee venom has also a prominent effect on the reticence of NFκB activation. Bee venom can also be used as an effective treatment of neuroinflammation and amyloidogenesis diseases like Alzheimer’s and the disease by the NF kappa B activation.
Sources:
Bee venom phospholipase A2 ameliorates Alzheimer’s disease pathology in Aβ vaccination treatment without inducing neuro-inflammation in a 3xTg-AD mouse model
Neuroprotective effects of bee venom phospholipase A2 in the 3xTg AD mouse model of Alzheimer’s disease
Bee venom ameliorates lipopolysaccharide-induced memory loss by preventing NF-kappaB pathway
Bee venom phospholipase A2 ameliorates Alzheimer’s disease pathology in Aβ vaccination treatment without inducing neuro-inflammation in a 3xTg-AD mouse model
Neuroprotective effects of bee venom phospholipase A2 in the 3xTg AD mouse model of Alzheimer’s disease
Bee venom ameliorates lipopolysaccharide-induced memory loss by preventing NF-kappaB pathway
