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Pharmacology & Pharmacy
Complementary therapies and phytonutrients derived from plant sources have been proposed as treatments for Parkinson’s disease. Numerous natural phytochemicals have emerged as therapeutically interesting compounds, drug entities, and phytochemicals for the treatment of inflammatory disorders. Additionally, numerous pharmacological studies have shown that phytochemicals are useful in treating neurodegenerative diseases (NDDs), depression, and dementia.
- neurodegeneration
- antioxidants
- phytoconstituents
1. Introduction
NDDs (neurodegenerative disorders) are a collection of disorders with various clinical implications and etiology. ALS (amyotrophic lateral sclerosis), cerebellar illness, Huntington’s chorea, Parkinson’s disease, Alzheimer’s, dementia, and schizophrenia are all examples of NDDs [1,2,3,4]. Age groups, hereditary diseases, non-enzymatic antioxidants, excitotoxicity, cytoskeletal abnormalities, autoimmunity, asymmetry, toxicity, elevated blood pressure, oxidative stress, and peripheral vascular diseases are subject to both experimental and epidemiological research. Some of the risk variables that have been discovered through the clinical manifestations of NDDs are associated with free radical toxicity, radical-mediated alteration, oxidase dysfunction, and endoplasmic reticulum stress caused by perinatal genetic abnormalities. The most important common symptoms are disturbances in balance, breathing, movement, reflexes, motor skills, or cardiac activity. Antioxidants such as flavonoids, polyphenols, and vitamins E and C can help to prevent these symptoms [5,6,7]. Antioxidants have a great impact on human health, as they can fight free radicals and, thus, halt the aging process and decrease the effects of oxidative damage caused by, for example, an unbalanced diet [8,9]. As a result, the long-term risk of neurodegenerative diseases is reduced (Figure 1). Although they can be treated, there is currently no cure for neurodegenerative diseases. Treatment of this disease relieves the symptoms in order to preserve the quality of life. Natural antioxidants, such as polyphenols, are becoming more popular because they can be obtained from foods and supplements and offer a range of health benefits [10]. Although it affects both males and females with increase in their age but males tend to be affected more frequently [11]. It is considered an international disease that does not distinguish between social class or race. The disease is estimated to affect 1% of people over the age of 65 worldwide, accounting for up to two-thirds of all people with movement disorders [12].
Figure 1. Role of Phytochemicals in the treatment of neurological diseases.
As the population ages, PD has become more prevalent, with those over 85 years old reaching 2.6%. The non-motor symptoms that patients with PD encounter include pain, exhaustion, autonomic dysfunction, changed mood, sleep disturbance, and cognitive abnormalities [13]. PD is referred to asa synucleinopathy because Lewy bodies, a crucial clinical characteristic of the disease, accumulate due to the misfolding of β-synuclein as a major feature. Furthermore, β-synuclein appears to be connected to both idiopathic and inherited forms of Parkinson’s disease and has a special role in the disease’s pathogenesis. It is worth noting that β-synuclein buildup has been closely linked to posttranslational modifications, systemic inflammation, oxidative stress, mitochondrial biogenesis, changed mitochondrial physical properties, synapse dysfunction, glycolipids, ER stress, and metal complexes. The overproduction of ROS and years of age breakdown the antioxidant defense system and increase oxidative stress in certainbrain areas, which can contribute to the misfolding of β-synuclein being the catalyst for the aging process in PD [14,15]. Although it is not a cure, levodopa has emerged as an efficacious drug for PD’s first motor symptoms. Despite the fact that stiffness and bradykinesia respond the best, tremors may only be somewhat reduced by levodopa. Other symptoms, such as balance issues, may worsen. L-dopa, however, cannot be used to treat Lewy disease, non-motor symptoms, or neuronal loss [16]. Patients require greater L-dopa doses over time, which is accompanied by a rise in side effects such as dyskinesias. Amantadine, an antiviral medication, appears to alleviate motor problems as well. Medicines based on dopamine agonists are also administered to address a range of neuromotor symptoms that are associated with disease progression. The long-term use of conventional PD medications can lead to adverse effects, such as dyskinesias and motor fluctuations (Table 1). As a result, novel therapeutic techniques used to prevent neurodegeneration, non-motor symptoms, Lewy disease accumulation, or synuclein aggregation in the brain are required [17,18].
Table 1. Side effects of synthetic drugs.
| Synthetic Drug | Toxicity | References |
|---|---|---|
| Levodopa | Motor complications, dyskinesias, motor fluctuations | [19] |
| Dopamine Agonists | Hallucinations, impulse control disorders, excessive daytime sleepiness | [20] |
| MAO-B Inhibitors | Potential hypertensive crises, interactions with medications and certain foods | [21] |
| Anticholinergic Drugs | Cognitive decline, memory impairment, dry mouth, urinary retention | [22] |
| COMT Inhibitors | Hepatotoxicity, liver dysfunction | [23] |
2. Complementary Therapies for PD
Complementary therapies and phytonutrients derived from plant sources have been proposed as treatments for Parkinson’s disease [24]. Numerous natural phytochemicals have emerged as therapeutically interesting compounds, drug entities, and phytochemicals for the treatment of inflammatory disorders [25]. Additionally, numerous pharmacological studies have shown that phytochemicals are useful in treating neurodegenerative diseases (NDDs), depression, and dementia [26,27,28,29,30]. Physiologically active phytochemicals are important therapeutically because they serve as the antioxidant defense system’s primary and secondary metabolites, which protect against a variety of stress-related disorders and clinical symptoms [31]. These phytochemicals’ positive and therapeutic effects include antioxidant capacity, pathogen prevention, immune system activation, and nutritional support for healthy living cells [32]. Botanical substances, with their active phytonutrients, efficiently salvage oxygen-based free radicals, influencing the antioxidative defense system and contributing to major cognitive impairments such as dyskinesias, residual tremors, muscle stiffness, and instability [33]. (Figure 2).
Figure 2. Different natural antioxidants used in the treatment of PD.
3. Pathogenesis
Dopamine levels in the caudal nucleus, striatum, and expression medium fall as a result of the death of dopaminergic neurons in the substantia nigra pars compacta, which is associated with Parkinson’s disease. The progressive loss of cholinergic neurons is the most significant pathogenic discovery in Parkinson’s disease sufferers’ brains. For this reason, with the loss of these neurons, the dopamine levels fall. When 50–60% of the dopamine pathway is shut down and striatal dopamine levels are lowered by 80–85%, symptoms of the disease arise. However, Parkinson’s disease may have multiple etiological factors, including mitochondrial dysfunction, neuroinflammation, oxidative stress, and the formation of protein kinases called Lewy bodies in the cytosol (Figure 3) [34].
Figure 3. Pathogenesis of Parkinson’s Disease.
4. Phytochemicals and Parkinson’s Disease
Neurodegenerative diseases, including Parkinson’s disease, contributes to N increase in nicotinamide adenine dinucleotide phosphate oxidase and intracellular RNS, and, thus, result in cell damage due to oxidative stress [35].
Free radicals also damage cell membranes by oxidizing proteins, lipids, and nucleic acids, causing peptide cross-links [36]. The antioxidant and chelating effects of flavonoids and terpenoids are believed to be accountable for their therapeutic effects. Terpenoids, phenols, and flavonoids show important neuroprotective effects, due to their oxidative capacity [37]. By releasing extra protons, flavonoids scavenge superoxide, hydroxyl, and peroxyl radicals by donating an extra proton. This prevents ROS generation by the formation of complex structures containing dihydroxy groups, copper, multiple ions of transition metals, and iron [38].
Glutathione reductase, septo-optic dysplasia, and glutathione-S-transferase (GST) are the polyphenols that activate antioxidant enzymes. Polyphenols can raise the antioxidant levels by enhancing cell-signaling pathways through these enzymes. By generating unsaturated carbon–carbon double bonds with lipid bilayers, these phenolic acids inhibit lipid peroxidation and, thus, work as a powerful therapeutic and preventative agent [39].
The lack of oxygenation of the rings is assumed to be responsible for chrysin’s chemical capabilities, which include anti-inflammatory and antioxidant potential [40]. Diverse structures of flavones have been discovered to increase the capacity of antioxidant enzymes and also work in inhibiting COX-2, which is a pro-inflammatory mediator. Experiments with xanthine oxidase demonstrate that chrysin dramatically reduces ROS production. It is worth noting that rodent models require polyphenol dosages ranging from 10 µM to 100 µM to exercise their putative antioxidant and anti-inflammatory properties [41].
This entry is adapted from the peer-reviewed paper 10.3390/ph16070908
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