Neurodegenerative diseases (NDDs) are a major public health concern worldwide, leading to high rates of mortality and disability. These diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), are characterized by the progressive degeneration of neurons, leading to cognitive, motor, sensory, and behavioral impairments. Traditional Chinese Medicine (TCM), particularly Astragalus membranaceus (AM), has shown potential in treating these conditions. This article aims to provide a comprehensive review of the therapeutic effects and molecular mechanisms of Astragalus polysaccharides (APS) in treating neurodegenerative diseases.
| Medical Concept | Simplified Explanation | Relevant Details | Examples |
|---|---|---|---|
| Neurodegenerative Diseases | Diseases that cause the gradual loss of nerve cells in the brain and nervous system. | These diseases affect memory, movement, and thinking. Common types include Alzheimer’s, Parkinson’s, and Multiple Sclerosis. | A person with Alzheimer’s may have trouble remembering recent events. |
| Alzheimer’s Disease (AD) | A brain disorder that slowly destroys memory and thinking skills. | AD is the most common cause of dementia in older adults. It involves the build-up of harmful proteins in the brain, leading to nerve cell death. | Forgetting important dates or repeating the same question multiple times. |
| Parkinson’s Disease (PD) | A disorder of the nervous system that affects movement. | PD is caused by the loss of dopamine-producing brain cells. Symptoms include tremors, stiffness, and difficulty with balance and coordination. | A person with PD might have shaky hands and slow movements. |
| Multiple Sclerosis (MS) | A disease where the immune system attacks the protective covering of nerve fibers. | MS disrupts communication between the brain and the rest of the body. Symptoms can include vision problems, muscle weakness, and coordination issues. | A person with MS might feel very tired and have trouble walking. |
| Astragalus membranaceus (AM) | A plant used in traditional Chinese medicine for various health benefits. | AM is believed to boost the immune system, protect the liver, act as an antioxidant, and help with heart health. It contains compounds like flavonoids and polysaccharides. | Drinking tea made from AM roots to boost the immune system. |
| Astragalus Polysaccharides (APS) | Natural sugar compounds found in the Astragalus plant that have various health benefits. | APS have antioxidant, anti-inflammatory, and immune-boosting properties. They are studied for their potential in treating diseases like AD, PD, and MS. | APS may help reduce inflammation in the body, similar to how antioxidants work in fruits and veggies. |
| Immune Modulation | Adjusting the immune system to improve health. | This can involve boosting the immune response to fight infections or reducing it to prevent overreactions, such as in autoimmune diseases. | Taking vaccines to boost immunity or drugs to reduce inflammation in rheumatoid arthritis. |
| Antioxidant Effects | Protecting the body’s cells from damage caused by harmful molecules called free radicals. | Antioxidants neutralize free radicals, which can cause cell damage and contribute to aging and diseases like cancer. | Eating fruits and vegetables high in antioxidants like vitamins C and E. |
| Hepatoprotective | Protecting the liver from damage. | Substances with hepatoprotective properties help prevent liver damage caused by toxins, drugs, or diseases. | Milk thistle is a common herbal supplement known for its hepatoprotective effects. |
| Neuroprotective | Protecting nerve cells from damage, degeneration, or impairment. | Neuroprotective agents help maintain nerve cell function and prevent diseases like AD, PD, and MS. | Omega-3 fatty acids are known for their neuroprotective properties. |
| Anti-inflammatory Effects | Reducing inflammation, which is the body’s response to injury or infection. | Chronic inflammation can lead to various diseases. Anti-inflammatory substances help reduce this inflammation and promote healing. | Using ibuprofen to reduce inflammation and pain from arthritis. |
| Blood-Brain Barrier | A protective barrier that prevents harmful substances from entering the brain. | The blood-brain barrier allows essential nutrients to pass while blocking toxins and pathogens. Some medications are designed to cross this barrier to treat brain diseases. | Certain antibiotics are specifically formulated to penetrate the blood-brain barrier and treat meningitis. |
| Oxidative Stress | Damage caused by an imbalance between free radicals and antioxidants in the body. | Oxidative stress can damage cells, proteins, and DNA, leading to aging and diseases like cancer and neurodegenerative disorders. | Exposure to pollution or radiation can increase oxidative stress. |
| Insulin Resistance | When cells in the body don’t respond well to insulin, making it hard to regulate blood sugar levels. | Insulin resistance is a key feature of type 2 diabetes and can lead to high blood sugar levels and other metabolic problems. | Obesity is a common cause of insulin resistance, often leading to type 2 diabetes. |
| Autophagy | The body’s way of cleaning out damaged cells to regenerate newer, healthier cells. | Autophagy is crucial for cell maintenance and plays a role in preventing diseases like cancer and neurodegenerative disorders by removing damaged components. | Fasting is believed to promote autophagy, aiding in cellular repair and longevity. |
| Cognitive Function | The mental processes involved in gaining knowledge and understanding. | This includes processes like memory, attention, language, problem-solving, and decision-making. Cognitive function declines in conditions like AD and other dementias. | Brain exercises, like puzzles and learning new skills, can help maintain cognitive function. |
| Mitochondrial Dysfunction | When the mitochondria (the energy-producing parts of cells) don’t work correctly. | Mitochondrial dysfunction is linked to numerous diseases, including neurodegenerative disorders, as it affects energy production and cell survival. | Mitochondrial diseases can cause muscle weakness and neurological problems. |
Detailed Overview of Astragalus membranaceus
Astragalus membranaceus, a perennial herb widely used in TCM, is primarily found in China, Mongolia, and Korea. It grows in temperate and subtropical regions and is known for its stout, cylindrical roots covered with yellow-brown skin and yellow-white inner part. The primary medicinal part is the root, which is used for its immune-boosting, antioxidant, hepatoprotective, diuretic, antidiabetic, anticancer, and expectorant properties. AM contains various bioactive compounds, including flavonoids, saponins, and polysaccharides, which contribute to its pharmacological effects.
Biological Activities of Astragalus Polysaccharides
APS, the main bioactive component of AM, exhibits numerous biological activities, such as immunomodulatory, antioxidant, antitumor, antidiabetic, antiviral, hepatoprotective, anti-inflammatory, anti-atherosclerotic, hematopoietic, and neuroprotective effects. APS regulate immune cell activity, enhance insulin sensitivity, reduce oxidative stress, and protect neuronal health. These properties make APS a promising candidate for treating neurodegenerative diseases.
Pharmacokinetics of APS
Research on the pharmacokinetics of APS is relatively limited. APS are absorbed through passive pathways but have low absorption efficiency due to their large molecular weight and poor intestinal permeability. Enhancing their bioavailability through nanocarriers has shown promise. APS are distributed primarily in the liver, kidneys, spleen, lungs, and plasma. They improve blood-brain barrier permeability, enhancing their potential in treating neurological diseases. APS are metabolized by intestinal microbiota and exhibit low toxicity at conventional doses.
Therapeutic Effects and Mechanisms of APS on Neurodegenerative Diseases
Alzheimer’s Disease (AD)
Alzheimer’s disease (AD) is the most common form of dementia, affecting millions globally. The pathogenesis of AD is complex, involving amyloid-beta (Aβ) accumulation, tau hyperphosphorylation, oxidative stress, and inflammation. APS have shown potential in mitigating these pathological processes.
- Improving Insulin Resistance and Lowering Blood Glucose:
- Epidemiological studies suggest a link between type 2 diabetes (T2DM) and increased AD risk. APS improve insulin resistance and lower blood glucose levels, reducing AD risk.
- Studies on HFSTZ-induced AD mice show that APS reduce glucose intolerance and hyperinsulinemia, alleviating insulin resistance and improving cognitive function (Huang et al., 2017).
- Antioxidant and Anti-inflammatory Effects:
- APS activate the Nrf2 pathway, enhancing antioxidant defenses and reducing oxidative stress in AD models. This reduces cell apoptosis and Aβ accumulation, improving cognitive function (Qin et al., 2020).
- APS reduce neuroinflammation by modulating the JAK/STAT, Toll, and IMD pathways, which are involved in the inflammatory response in AD.
- Neuroprotective Effects:
- APS protect neurons by reducing the expression of pro-apoptotic factors such as Cyt C and Caspase-3/9, thereby preventing neuronal apoptosis (Qu et al.).
- APS enhance the structural integrity of neurons in the hippocampus, maintaining normal mitochondrial morphology and reducing Aβ-induced neurotoxicity (Fei et al., 2015).
Parkinson’s Disease (PD)
Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. APS have shown promise in protecting and repairing neurons and mitochondria, key aspects in preventing and treating PD.
- Promoting Autophagy and Reducing Oxidative Stress:
- APS promote autophagy in PC12 cells through the PI3K/AKT/mTOR pathway, enhancing cell proliferation and exerting anti-PD effects (Tan et al., 2020).
- APS alleviate oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, increasing antioxidant enzyme activities (Li et al., 2016).
- Neuroprotective and Anti-inflammatory Effects:
- APS reduce neuroinflammation by modulating immune response and reducing inflammatory cytokines in brain tissue (Chen and Zhou, 2015).
- APS increase the content of tyrosine hydroxylase, an enzyme crucial for dopamine synthesis, thereby supporting dopaminergic neuron function.
Multiple Sclerosis (MS)
Multiple sclerosis (MS) is an autoimmune inflammatory disease characterized by demyelination and axonal loss. APS have shown potential in alleviating MS symptoms and promoting myelin regeneration.
- Modulating Immune Response:
- APS inhibit T cell proliferation and reduce pro-inflammatory cytokine expression via the PD-1/PD-Ls pathway, alleviating experimental autoimmune encephalomyelitis (EAE), a model for MS (Sun et al., 2019).
- Promoting Myelin Regeneration:
- APS promote the differentiation of neural stem cells into oligodendrocytes and activate the Sonic hedgehog signaling pathway, essential for myelin regeneration (Ye et al., 2021).
Future Directions and Conclusion
APS are promising candidates for treating neurodegenerative diseases due to their diverse pharmacological activities. Future research should focus on elucidating molecular mechanisms, conducting large-scale clinical trials, optimizing extraction and purification techniques, and developing new drug delivery systems. Personalized treatment strategies and combined applications with existing drugs could enhance the therapeutic potential of APS, making them a valuable addition to neurodegenerative disease management.
resource : https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1449101/full
