Neuroprotective Mechanisms of Phytochemicals in Alzheimer’s, Parkinson’s, and Huntington’s Diseases: A Review
Rachel Brownridge, Taylor Elb, Tina MacQuarrie, and Erica Todd
Undergraduate Students, University of Guelph
Introduction
Throughout history, medicinal plants have been used by healers and in traditions across many cultures, each with its own unique theories, treatments, and therapies (Khan, 2014). Medicinal plants have been incorporated into our food choices, oils, poisons, lotions, and even prescription drugs due to the various benefits they provide (Xiao & Bai, 2019). These treatments have been believed to improve overall health and wellness and to prevent illness (Khan, 2014). While today we use more prescription drugs for ailments, the benefits of these plants are not forgotten. Studies have investigated the effectiveness of certain medicinal plant compounds in treating diseases such as neurodegenerative disorders. However, the exact mechanisms underlying this effect remain unknown (Kumar & Khanum, 2012).
One of these aspects is phytochemicals found in plant species. Phytochemicals are naturally occurring bioactive compounds found in many foods, such as vegetables, fruits, and nuts (Xiao & Bai, 2019). These phytochemicals are Phenolics, Alkaloids, Terpenes, Saponins, Glycosides, Polysaccharides, and Organosulfur compounds (Xiao & Bai, 2019). Each has its own unique identifiers and benefits. Polyphenols are bioactive secondary metabolites that are classified into several subgroups, including flavonoids and non-flavonoids (Ayaz et al., 2019). Alkaloids are chemical compounds that contain a nitrogen atom in the carbon ring of their chemical structure (Cassiano, 2010). Similarly, Terpenes are simple hydrocarbons composed of five-carbon isoprene units, with or without oxidized methyl groups (Perveen, 2018). Saponins are glycosides of triterpenoid or steroidal aglycones whose biological functions are determined by their structure (Sun et al., 2015). Polysaccharides are carbohydrates, with at least 10 connected monosaccharides (Wang et al., 2022). In addition, glycoside phytochemicals are carbohydrates that contain a glycone and sugar group (Zhou et al., 2025). Finally, organosulfur compounds contain sulfur in their chemical structure and can be either oil- or water-soluble (Gambari et al., 2022). Overall, each of these phytochemicals has benefits that can improve human health and prevent diseases.
This paper will discuss phytochemicals as neuroprotective agents and the potential benefits they can provide to people suffering from neurodegenerative diseases. These neurodegenerative diseases result from progressive neuronal loss and affect the nervous system (Utpal et al., 2025). These diseases are also associated with synaptic dysfunction and alterations in brain protein phosphorylation (Lamptey et al., 2022). While under the same umbrella, each neurodegenerative disease has its own characteristics and effects. This paper will discuss Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). Alzheimer’s disease is a major neurodegenerative disease that causes memory, learning, and many other cognitive functions to worsen (Hussain et al., 2018). Much is unknown about this disease, but studies have found it to be linked to 80% of dementia cases (Alrouji et al., 2024). In contrast, Parkinson’s disease is a progressive neurological disease that leads to tremors, muscle stiffness, and coordination difficulties that affect walking and balance (Lamptey et al., 2022). Huntington’s disease is a genetic disorder caused by a longer CAG repeat in the HTT gene, leading to problems with huntingtin protein. This causes mitochondrial disruption and oxidative stress (Alqahtani et al., 2023). Each phytochemical can improve symptoms and progression in patients suffering from these debilitating neurodegenerative diseases and can expand scientific understanding of the role phytochemicals can have on our systems.
1. Polyphenols
Polyphenols are the largest type of phytochemicals with two major subsections, flavonoids and non-flavonoids. They are plant-derived bioactive secondary metabolites that are best known for their anti-inflammatory and antioxidant properties (Sharifi-Rad et al., 2022). Polyphenols were found to be able to pass through the blood-brain barrier, allowing them to interact directly within the brain (Ayaz et al., 2019). This led polyphenols to become an area of interest to scientists due to their key pathological mechanisms that have been shown to have neuroprotective properties that improve cognitive function and reduce neurodegeneration within neurodegenerative diseases (Chen et al., 2025).
1.1 Flavonoids
Flavonoids are the largest subsection of polyphenols with a basic/core structure of C6C3-C6, meaning that two benzene rings are joined by a three-carbon chain, thus forming a heterocyclic ring (Safe et al., 2021). Flavonoids can be broken down into six subgroups: flavones, flavonols, chalcones, anthocyanine, and isoflavones (Panche et al., 2016). They are found in many foods, such as fruits and vegetables. (Panche et al., 2016). Flavonoids are present in many flowers, primarily within their stems and roots, and are recognized in the pigment, specifically in the angiosperm families (Panche et al., 2016). Flavonoids have been shown to be one of the most important classes of phytochemicals for the enhancement of health benefits due to evidence showing that their use as nutraceuticals helps maintain health, treat neurodegenerative diseases, and help to maintain their symptoms (Safe et al., 2021).
Additionally, they alleviate symptoms, slow progression, and nutraceuticals create a treatment for neurodegenerative diseases because of their antioxidative, anti-inflammatory, and antiamyloidogenic properties (Ayaz et al., 2019). These properties help to target oxidative stress, neuroinflammation, and inhibition of key enzymes, which are key factors that cause neurodegenerative diseases (Ayaz et al., 2019).
1.1.1 Flavonoids in Alzheimer’s Disease
Flavonoids have been an area of research for many neurodegenerative diseases, specifically for Alzheimer’s disease and Parkinson’s Disease. Oxidative stress is a leading factor for Alzheimer’s symptoms and conditions and is present when there is a buildup of free radicals within the brain due to an insufficient quantity of antioxidants (Tucker & Cotman, 2021). This causes neuroinflammation, which results in neuron damage (Tucker & Cotman, 2021). Flavonoids are best known for their antioxidant properties, meaning they help increase antioxidant levels in the brain, thereby lowering free radical levels and lessening the cognitive symptoms of Alzheimer’s (Tucker & Cotman, 2021). An increase of amyloid-beta aggregation, which causes plaques to build up within the brain, has been shown to be a prominent factor within Alzheimer’s patients (Minocha et al., 2022). It has been discovered that nobiletin, a specific flavonoid, has been shown to reduce amyloid-beta aggregation within the hippocampus, which in turn lessens the amount of amyloid-beta plaques formed within the hippocampus (Minocha et al., 2022). This helps to prevent memory deficits (Minocha et al., 2022).
1.1.2 Flavonoids in Parkinson’s Disease
Dopaminergic neuron degeneration and death cause a reduction of a neurotransmitter called dopamine, and this is what causes many of the motor symptoms of Parkinson’s Disease (García-Aguilar et al., 2021). Flavonoids such as EGCG help to protect the dopaminergic neurons from degeneration by enhancing the signal of the neurotransmitter dopamine by preventing alpha-synuclein aggregation, which is the process that forms Lewy bodies (GarcíaAguilar et al., 2021).
1.2 Non-Flavonoids
Non-flavonoids are the second subgroup within polyphenols with a basic/core structure of a single phenol ring with either a benzoic acid derivative or cinnamic acid-derived backbone (Li & Duan, 2018). There is one main subsection within non-flavonoids called phenolic acids (Li & Duan, 2018). Phenolic acids are found in many foods that humans consume, such as fruits, wholegrains, nuts, turmeric, cocoa, coffee, and red wine (Godos et al., 2021). Phenolic acids have been found to have neuroprotectant features on neurodegenerative diseases through having cognition-enhancing effects on anti-amyloidogenic and anti-aggregate activity (Caruso et al., 2022). Phenolic acids inhibit the aggregation of proteins involved in different neurodegenerative diseases with cognitive deterioration, such as Alzheimer’s disease and Parkinson’s disease (Caruso et al., 2022).
1.2.1 Non-Flavonoids in Alzheimer’s Disease
A factor that is prominent within patients with Alzheimer’s is the amyloid-beta aggregation, and it is seen that those diagnosed with Alzheimer’s have an increased production of amyloid-beta, and this creates more amyloid plaques within the brain (Minocha et al., 2022). This causes damage to the neuron and, in severe cases, neuron death (Minocha et al., 2022). It has been seen that a non-flavonoid called curcumin prevents the accumulation of amyloid-beta within the brain if consumed or administered constantly for a long duration of time (Minocha et al., 2022). Tau tangles are one of the key drivers of neurodegeneration of Alzheimer’s disease, and certain non-flavonoids such as curcumin and resveratrol help to ensure that Tau tangles are lessened (Medeiros et al., 2011). They do this by blocking the enzymes that cause the Tau proteins to become hyperphosphorylated. In addition, they also prevent the misfolding of Tau proteins, thus keeping the Tau proteins in their healthy form (Medeiros et al., 2011). This helps the symptoms such as memory loss, confusion or disorientation, behavior/personality changes, and motor symptoms in Alzheimer patients (Medeiros et al., 2011).
1.2.2 Non-Flavonoids in Parkinson’s Disease
Non-flavonoids impact Parkinson’s Disease at the cellular and mitochondrial level. Examples of non-flavonoids that interact at that level are curcumin and phenolic acids (Yamamoto et al., 2023). They help to repair all the mitochondrial dysfunction, and by doing this, the non-flavonoids can enhance energy production in neurons, which then allows for oxidative stress to be reduced, thus allowing the cells to be able to form new healthy mitochondria (Yamamoto et al., 2023). Non-flavonoids are more focused on long-term cellular protection and ensure neuron health to prevent any neuron death (Yamamoto et al., 2023).
Polyphenols affect many more neurodegenerative diseases. However, there has not been enough research done to fully understand their benefits and how they impact these diseases. It has been shown that diet is extremely important for polyphenols because that is how they can be incorporated into everyday lives, thus helping promote long-term brain health and prevent neurodegenerative diseases everyday (Chen et al., 2025).
2. Alkaloids
Alkaloids are naturally occurring chemical compounds with a basic nitrogen atom in their structure and are found in approximately 20% of plant species as a chemical defense mechanism (Cassiano, 2010). The nitrogen atom’s position determines alkaloid classification and effects. Examples include nightshades, poppies, buttercups, Belladonna, and Amaryllis (Hussain et al., 2018). Alkaloids are used in medications for anti-cholinergic, antitumor, antiviral, antihypertensive, analgesic, antidepressant, myorelaxant, antimicrobial, antioxidant, and antiinflammatory properties (Cassiano, 2010). Morphine, an alkaloid, is widely used for pain management (Hussain et al., 2018). Alkaloids also affect cellular pathways and enzymes, which may help patients with neurodegenerative diseases, specifically AD and HD.
2.1 Alkaloids in Alzheimer’s Disease
As discussed previously, many phytochemicals, including alkaloids, have antioxidant properties that reduce oxidative stress in Alzheimer’s patients’ brains, improving symptoms and slowing disease progression (Alqahtani et al., 2023). For example, Morphine increases GABA levels in the brain, protecting against oxidative stress and neurotoxicity in AD (Hussain et al., 2018). Alkaloids also inhibit cholinesterase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidase (MAO) (Konrath et al., 2013). In AD, AChE and BChE degrade more acetylcholine (ACh), a neurotransmitter important for learning and memory (Konrath et al., 2013). Increased ACh degradation impairs cognition. Therefore, inhibiting these enzymes can slow symptom progression and improve patient condition (Konrath et al., 2013). The alkaloid Geissoschizoline also binds to the PAS enzyme, inhibiting the formation of neurotoxic AChE-Aβ complexes that contribute to neuronal loss in the Alzheimer’s brain (Lima et al., 2020). Thus, the alkaloid acts as a neuroprotector and slows AD progression. Alkaloids also counteract neuronal degeneration in AD due to neuroinflammation driven by increased microglial and astrocyte activation (Lima et al., 2020). These cells are activated in AD by AB plaques and release pro-inflammatory mediators, triggering inflammation and neural cell damage, creating a feedback loop of continuous inflammation (Lima et al., 2020). The antiinflammatory effects of alkaloids interrupt this loop and reduce inflammation around neural cells.
2.2 Alkaloids in Huntington’s Disease
Huntington’s disease (HD) causes neuronal cell death in the cerebral cortex, affecting motor and cognitive functions and reducing dopamine levels (Hussain et al., 2018). Since alkaloids offer many benefits, they could help manage HD symptoms due to their neuroprotective effects. Each class of alkaloid can have distinct interactions and effects on neurodegenerative diseases like HD. Kim et al. (2014) found that the alkaloid berberine reduces TH-positive cells involved in dopamine transport, thereby improving overall motor skills by preventing dopaminergic neuronal damage. Alkaloids were also found to improve memory impairment, motor function, and grip strength in HD. However, further research is required (Kim et al., 2014; Jiang et al., 2015). Like in AD, alkaloids inhibit AChE, BChE, and MAO in HD, with similar benefits. However, they also upregulate nuclear factor erythroid-2 (Nrf2) and phosphorylate protein kinase-B, which help defend against oxidative damage and neural cell apoptosis (Jiang et al., 2015). Alkaloids also upregulate GLP-1 (glycagon-like protein 1) and CREB, which help preserve dopaminergic neurons and slow neurological decline (Jiang et al., 2015). Berberine could also reduce the accumulation of the mutant Htt gene that causes HD by increasing autophagic function, however, this requires further research (Jiang et al., 2015).
3. Terpenes and Saponins
Terpenes comprise one of the largest and most diverse group of secondary metabolites that are found in plants (Cox-Georgian et al., 2020). Terpenes are simple hydrocarbons that consist of five carbon isoprene units (Perveen, 2018). Terpenoids are a specific class of modified terpenes that have different functional groups and have oxidized methyl groups that have been moved or removed. Terpenes can be further divided into five groups based on their carbon units: monoterpenes, sesquiterpenes, diterpenes, sesterpenes, and triterpenes. These compounds have many functions in plants, including, but not limited to, plant fragrance, taste, and pigment, all of which are useful in defending against herbivores (Cox-Georgian et al., 2020).
Throughout history, terpenes have been employed for a wide range of human uses. One of their most well-known roles is as the main bioactive component in essential oils (Masyita et al., 2022). Essential oils are highly concentrated and volatile liquids that are extracted from plant material. They have been used in medicine, perfumery, cosmetics, and for their flavour (Hyldgaard et al., 2012). Recent research has pointed towards terpenes being used as a treatment for AD, as they have been found to produce some key neuroprotective effects.
Saponins are classified as glycosides whose structure contains one or more sugar chains and either a steroidal or triterpenoid aglycone (Sun et al., 2015). Saponin-containing plants, such as ginseng, have a long history within traditional Chinese medicine. While saponins vary in their composition, those present within cultivated plants are predominantly triterpenoids (Abduljawad et al., 2022) and thus produce effects similar to terpenes as a whole. In recent history, saponins have been gaining attention for their neuroprotective properties (Sun et al., 2015). Seeing as currently available treatments for neurodegenerative diseases tend to be slow to develop and limited in their treatment abilities (Abduljawad et al., 2022), saponins appear to be a promising alternative, though information on their use as a treatment, as with most phytochemicals, is still in its infancy.
3.1 Terpenes and Saponins in Alzheimer’s Disease
One of the main hallmarks required for the diagnosis of AD is abnormal beta-amyloid plaque production and aggregation (Murphy & LeVine, 2010). The production and extracellular plaque deposition of beta-amyloid peptide are believed to be the main driving forces of AD progression (Sehar et al., 2022). This peptide is normally present in the brain without issue, but when in excess, it induces synaptic dysfunction, disrupts neural connectivity, and is associated with neuronal death (Karisetty et al., 2020). Certain terpenes have been found to be able to help balance beta-amyloid production and deposition, one example of which is found in Panax ginseng, a triterpenoid saponin (Yang et al., 2009). This plant contains various ginsenosides, such as Rg3, that are able to mitigate beta-amyloid peptide overproduction by promoting its degradation. This occurs through enhancing neprilysin gene expression, which is a beta-amyloiddegrading enzyme.
Neuroinflammation in AD can result from beta-amyloid plaque accumulation but can be exacerbated by factors such as systemic inflammation and cerebral trauma (Kamila et al., 2025). As a result, microglia are activated and produce pro-inflammatory cytokines (Kinney et al., 2018). This immune response is associated with neurodegeneration but also has been found to exacerbate Aβ plaque production and intracellular neurofibrillary tangle formation, creating a feedback loop. Many terpenes exhibit anti-inflammatory properties, such as the phenylpropyl triterpenoid 3β-trans-p-coumaroyl acid and its derivatives, extracted from Osmanthus fragrans leaves (Jeong et al., 2020). These have been found to reduce pro-inflammatory cytokine levels, thus having the potential to mitigate this cycle’s effects and prevent neuronal degeneration.
AD treatment generally relies on AChE inhibitors, which aim to compensate for neuronal death by inhibiting ACh turnover (Rees, T.M. & Brimijoin, S., 2003). AChE has been consistently found alongside the characteristic amyloid deposits found in AD (Gajendra et al., 2024). This enzyme breaks down ACh, which is heavily involved in memory and learning ability (Rees, T.M. & Brimijoin, S., 2003). Thus, excess AChE produces the memory and cognitive decline seen in AD. Current synthetic ACh inhibitors are limited in their ability to aid affected patients, as they often have significant side effects that impact quality of life. Some promise has been shown in recent research into alternative herbal remedies. In particular, Salvia lavandulaefolia essential oil has been found to improve cognitive function in some cases of mild to moderate AD (Perry et al., 2000). The main terpenes present in this extract were camphor, 1,8-cineole, α- and β-pinene, and bornyl acetate. It should be noted that this essential oil’s inhibitory activity is likely the result of synergistic effects among constituents, as none of the contents were noted to be particularly potent.
3.2 Terpenes and Saponins in Parkinson’s Disease
The progression of PD is related to changes occurring in the extracellular matrix of the brain, particularly those which affect the survival of dopaminergic neurons (Ramesh & Arachchige, 2023). It is the depletion of dopamine that is thought to produce the characteristic motor deficits and cognitive deficits that are seen in PD.
The intracellular aggregation of alpha-synuclein is a key feature of PD progression (Ramesh & Arachchige, 2023). Misfolded and aggregated alpha-synuclein form Lewy bodies within the cell body, which are a pathological hallmark of PD and are associated with dopamine reduction (Baggett et al., 2024). Thus, common approaches to treating PD involve promoting the degradation of these aggregates. It is currently understood that chaperone-mediated autophagy and macroautophagy, two mechanisms within the lysosomal autophagy system, play a key role in degrading alpha-synuclein (Ramesh & Arachchige, 2023). It is the inhibition of either of these mechanisms that is thought to result in alpha-synuclein aggregation to the point of producing the effects seen in PD. Terpenes have shown promise in their ability to promote the clearance of alpha-synuclein through these pathways (Gupta & Sashidhara, 2023). One key example is celastrol, which is isolated from Tripterygium wilfordii Hook F. (Ng et al., 2022). This plant has long been used in traditional Chinese medicine, specifically for its anti-inflammatory and immune-modulating properties (Song et al., 2020). In relation to PD treatment, the terpene celastrol was found to regulate the processing of alpha-synuclein by promoting activation of the autophagic pathway. ACT001, another terpene, was also found to inhibit alpha-synuclein aggregation, but instead through its neuroprotective effects (Liu et al., 2020). When combined with a low dose of L-DOPA, a common treatment for PD, it resulted in a significant ability to prevent dopaminergic neuron loss. In terms of saponins, those found in Panax notoginseng have been found to display neuroprotective effects on dopaminergic cells, specifically through their ability to activate the growth factor receptor (IGF-IR) pathway (Xu et al., 2009).
4. Organosulfur Compounds
Organosulfur compounds are compounds that contain sulfur. They can be divided into water-soluble and oil-soluble compounds. Not all of them are phytochemicals, but in the context of the ones that are, they are defined as naturally occurring sulfur-containing molecules that are found in plants and have bioactive effects that are helpful to the plant’s survival. Organosulfur compounds are most prevalent in plants in the Allium and Brassica genera. For example, garlic and onion for Allium and broccoli and cabbage for Brassica (Gambari et al., 2022).
Table 1: Organosulfur Phytochemicals Found in Garlic.
4.1 Organosulfur Compounds in Alzheimer’s Disease
Like the previously mentioned phytochemicals, the antioxidant properties of organosulfur compounds can reduce the presence of reactive oxygen species and, therefore, oxidative stress (Tang et al., 2025). Aged garlic extract contains certain organosulfur compounds such as Sallylcysteine, because of these compounds, the extract can aid in slowing the progression of the disease by decreasing protein oxidation, lipid peroxidation, DNA fragmentation, and endoplasmic reticulum stress (Goncharov et al., 2021). Due to S-allylcysteine along with other phytochemicals, aged garlic extract can also reduce neurotoxicity caused by amyloid-beta plaque formation (Carmia, 2006).
4.2 Organosulfur Compounds in Parkinson’s Disease
Certain organosulfur compounds, such as allicin, are antioxidants and can reduce intracellular reactive oxygen species. By reducing the reactive oxygen species, the compounds protect from damage to the neurons caused by oxidative stress and, therefore, slow the progression of Parkinson’s disease (Rakshit et al., 2023). Oftentimes, neuro-inflammation is exacerbated through reactive oxygen species, inducing certain proteins that interact with inflammatory genes. Therefore, by impeding certain oxidative reactions, organosulfur compounds also provide neuro-anti-inflammatory benefits (Rakshit et al., 2023). Reactive oxygen species are also elevated by mitochondrial dysfunction, a key occurrence in PD, which also leads to elevated levels of lipid peroxidation and neurodegeneration. Allicin, along with some other organosulfur compounds, can reduce this by inhibiting mitochondrial dysfunction in 6-hydroxydopamine, a neurotoxin that produces free radicals when undergoing metabolic degeneration and auto-oxidation (Rakshit et al., 2023).
4.3 Organosulfur Compounds in Huntington’s Disease
Sulforaphane, a small organosulfur compound found in Brassica plants, has shown promise as being used in the treatment of Huntington’s Disease because it can cross the bloodbrain barrier and could possibly prevent the accumulation of the mutant Huntington protein because of its potential to increase proteasomal degradation and autophagy (Liu et al., 2014). These are important processes in slowing the progression of neurodegeneration because they degrade mutant proteins and, therefore, stop them from forming aggregates. Sulforaphane also has the potential to reduce oxidative stress through its ability to reduce free radicals. Sulforaphane has yet to be tested clinically with regard to the treatment of HD (Liu et al., 2014). Nevertheless, this knowledge could be beneficial in the treatment of a variety of neurodegenerative diseases.
5. Glycosides and Polysaccharides
Glycosides and polysaccharides are carbohydrates, with polysaccharides containing at least 10 monosaccharides connected through glycosidic bonds (Wang et al., 2022) and glycosides containing a slightly polar aglycone and a polar sugar group. Glycosides can be divided into different groups based on the atom that attaches the sugar group to the aglycone, or the structure of the aglycone (Zhou et al., 2025). Not all polysaccharides and glycosides are classed as phytochemicals. Only the ones that are plant-derived can be classed as such. Examples of these include iridoid glycosides, phenylpropanoid glycosides, fructan, and plantspecific polysaccharides.
5.1 Glycosides and Polysaccharides in Alzheimer’s Disease
Plant-based glycosides and polysaccharides have many properties that can aid in the treatment of AD and improve the patient’s quality of life. They can decrease the chronic neuroinflammation associated with the disease by inhibiting signaling pathways that release proinflammatory factors (Zhou et al., 2025). Autophagy and lysosome dysfunction are key components in AD because, without the regulatory effects of these processes, the accumulation of beta-amyloid plaques and neurofibrillary tangles caused by hyperphosphorylated tau proteins is more prevalent. Certain glycoside and polysaccharide phytochemicals can increase autophagy along with lysosomal function, thereby reducing the accumulation of harmful proteins and the associated oxidative stress and decreased neuronal function (Zhou et al., 2025). They do this through the regulation of multiple pathways, whether that be inhibiting detrimental pathways or activating beneficial ones.
5.2 Glycosides and Polysaccharides in Parkinson’s Disease
The dopaminergic neurodegeneration that characterizes PD is correlated with oxidative stress, atypical aggregation of the protein alpha-synuclein, neuroinflammation, and abnormal autophagy (Wang et al., 2022). As previously mentioned, plant-derived polysaccharides and glycosides have properties that can aid in the regulation of these events. Certain polysaccharides, such as ones extracted from the plant M. charantia, can inhibit oxidative stress in the brain and, as a result, lead to an increased dopamine level and, therefore, reduced symptoms (Wang et al., 2022). The main cause of neuro-inflammation in PD is pro-inflammatory cytokines in the brain, causing immune cells to be triggered. As a result, neurodegeneration is exacerbated. Polysaccharides from many different plants have been effective in acting as an antineuroinflammatory. There’s research showing that this might be the case for some plant glycosides as well (Yao et al., 2025). Autophagy must have proper regulation for normal brain function. Too little causes detrimental protein accumulation, and too much causes increased neuron degradation. Specific compounds such as astragalus polysaccharides have proven beneficial in improving impaired autophagy, while others, such as Lycium barbarum polysaccharides, have proven beneficial in decreasing overactive autophagy (Gan et al., 2023).
5.3 Glycosides and Polysaccharides in Huntington’s Disease
As a consequence of the gene mutation in HD, the Huntington protein is abnormally folded. This mutant protein is neurotoxic and causes the degradation associated with the disease (Wang et al., 2022). Certain plant polysaccharides and glycosides have shown promise in the treatment of the disease. For example, Lycium barbarum polysaccharides can reduce the toxicity of the mutant Huntington protein by activating the Akt protein, a compound that has a negative relationship with the mutant Huntington protein (Wang et al., 2022). Oxidative stress and neuroinflammation are caused by the toxicity of the mutant Huntington protein. As mentioned previously, many plant polysaccharides and glycosides have antioxidant and anti-inflammatory effects and, therefore, may be beneficial in the treatment of HD. According to one study, the glycoside naringin has been observed to have these benefits in the treatment of the disease in rats (Cui et al., 2018). Another study demonstrated that polysaccharides from the family Berberidaceae can have similar impacts on roundworm HD models (Wang et al., 2022).
6. Conclusion
In conclusion, the above-discussed phytochemicals, polyphenols, alkaloids, terpenes, saponins, organosulfur chemicals, glycosides, and polysaccharides each have their own unique benefits that can improve symptoms and progression of neurodegenerative diseases. They affect AD by providing antioxidant properties, decreasing neuroinflammation via anti-inflammatory properties, lowering the amount of tau tangles and amyloid-beta plaques, increasing autophagy, and lysosomal function. In addition, they inhibit the enzymes cholinesterases, AChE, BChE, MAO, and PAS to obtain positive effects on AD symptoms. Phytochemicals also affect HD by improving dopamine transport, increasing autophagy and proteasomal degradation, reducing mutated Huntington protein levels, providing antioxidant and anti-inflammatory properties, upregulating Nrf2, GLP-1, and CREB, and phosphorylating protein kinase-B. These effects could generally be linked to their inhibitory function on the enzymes AChE, BChE, and MAO. Furthermore, phytochemicals impact PD by helping mitigate dopaminergic neuron degeneration by improving mitochondrial function and acting as antioxidants and anti-inflammatories. While phytochemicals have shown promise in treating such symptoms, research is currently not developed enough for them to fully replace existing treatments. However, they appear to be key potential future avenues that should be further researched in both pre-clinical and clinical settings.
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