Phytochemicals in Alzheimer’s Prevention: Causes and Potentials

Yijia Li

Beijing Number 4 High School International Campus, Beijing, China

Keywords: Alzheimer's Disease Prevention, Phytochemicals, Neuroprotection.

Abstract: Alzheimer’s disease is a prevalent neurodegenerative disorder around the world, characterized by amyloid-

beta (Aβ) aggregation and tau hyperphosphorylation, affecting more than 55 million of people worldwide.

The pathogenesis of Alzheimer’s disease is a complex issue, influenced by aging, air pollution, toxic metals,

chronic diseases, and diet. While current treatments provide limited symptomatic relief, phytochemicals,

including flavonoids, polyphenolic compounds, alkaloids, terpenes, and polysaccharides, particularly

traditional Chinese herbs, have demonstrated their unique potential in AD prevention and therapy. These

plant-based substances show potentials in mitigating oxidative stress, reducing neuroinflammation, and

enhancing mitochondrial function. This review offers a detailed analysis of typical medicinal plants,

especially rose flavonoids, and provides a comprehensive view of both the role of plant-based bioactive

substances as a promising alternative in AD prevention and current challenges, like bioavailability and brain

penetration. Despite these obstacles, innovative solutions are being explored to improve their therapeutic

efficacy.

1 INTRODUCTION

Alzheimer’s disease (AD) is the most common form

of dementia, characterized by cognitive deficits,

behavioral abnormalities, and impaired social

functioning, posing a significant public health

concern due to its high mortality rate worldwide

(Knopman et al. 2021). As a progressive disorder, the

progression of AD can be divided into several stages:

the preclinical stage, which lasts several years or

more, during which patients exhibit only mild

symptoms without functional impairment in daily life

or clinical signs; the early stage, marked by the onset

of more obvious symptoms, including memory loss,

reduced concentration, mood changes, and difficulty

distinguishing time and place; the moderate stage,

characterized by increased memory loss and

difficulties with reading, writing, and speaking; and

the severe stage, where symptoms may lead to the

patient’s death (Wang et al. 2020). At present, AD

affects more than 55 million patients globally, a

number that likely underestimates the true prevalence

due to limitations in medical testing in some regions.

Moreover, the number is predicted to double every

five years, reaching 115 million by 2050 (Jia et al.

2020). In China, approximately 9.83 million people

aged 60 and above are suffering from AD, according

to a national cross-sectional study in 2020 (Kumar et

al. 2020). China has ranked at the top of the incidence

rate of AD around the world since 2024, with up to

17 million AD patients. Amyloid-β (Aβ) plaque

deposition and hyperphosphorylated Tau protein

are the most prominent pathogenic features of AD.

Additionally, studies have demonstrated other

consequences of AD, including oxidative stress,

neuroinflammation, programmed cell death, and

metabolic imbalance, all of which contribute to the

progression of the disease (Wang et al. 2020).

Currently, there are two main hypotheses related to

the pathogenesis of AD: the cholinergic hypothesis,

linking cognitive decline to a reduction in

acetylcholine (ACh) and the amyloid hypothesis,

proposing that the accumulation of Aβ peptides

leads to neurotoxicity, tau pathology, and neuronal

death. While Aβ deposition occurs with normal

aging, in AD, genetic mutations accelerate its

buildup, particularly in inherited forms of the

disease, making Aβ accumulation a central factor in

AD progression (Scheltens et al. 2021, Hou et al.

2019).

Currently, existing drugs and treatments for

Alzheimer’s disease (AD) can only partially

alleviate symptoms and do not provide a complete

cure. Thus, further investigation into strategies for

Li, Y.

Phytochemicals in Alzheimer’s Prevention: Causes and Potentials.

DOI: 10.5220/0014401200004933

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 1st International Conference on Biomedical Engineering and Food Science (BEFS 2025), pages 90-99

ISBN: 978-989-758-789-4

the prevention and treatment of AD is necessary. As

an innovative and potentially effective alternative

approach, phytochemicals have gained increasing

attention. Phytochemicals, natural compounds

found in plants, offer a variety of health benefits.

These compounds, including polyphenols,

flavonoids, vitamins, and organosulfur compounds,

demonstrate antioxidant, anti-inflammatory, and

neuroprotective properties. By modulating key

biological mechanisms, phytochemicals can help

mitigate the pathological processes of AD. In recent

years, a growing number of studies have focused on

using active ingredients from phytochemicals to

treat AD, highlighting the potential efficacy of

medicinal plants in reducing AD risk. In addition,

medicinal plants have been used for Alzheimer’s

disease prevention in many countries, including

China, India, and Japan. In China, they make up

over 40% of the pharmaceutical market (Abate et

al. 2017). The promising potential of

phytochemicals in managing AD progression has

attracted global interest in plant-derived solutions

for neurodegenerative diseases. This paper extends

an in-depth study on the inhibitory effects of rose

flavonoids on Alzheimer’s disease, further

exploring the role of phytochemicals in AD

prevention. The research investigates the impact

of plant-based compounds, specifically rose

flavonoids, on neurodegenerative diseases. By

creating an in vitro AD model with neuronal cells

and microglia, sequencing cell samples, and

supplementing the model with rose flavonoids, the

study evaluates changes in gene expression, protein

levels, and signaling pathways. These findings

suggest a promising approach for delaying AD

progression and highlight the potential of

phytochemicals in AD management. The purpose of

this review is to provide a concise overview of the

pathogenesis of AD, and risk factors, emphasizing

how phytochemicals can be utilized in AD

prevention. Additionally, it analyzes the current

status of phytochemical-based treatments for AD in

different regions.

2 THE PATHOGENESIS OF

ALZHEIMER’S DISEASE

Alzheimer’s disease (AD) is a progressive

neurodegenerative disorder driven by Aβ

aggregation, tau hyperphosphorylation, metal-

dependent toxicity, and oxidative stress.

2.1 Aβ Aggregation

One of the hallmark features of Alzheimer’s disease

is the accumulation of Aβ aggregates, specifically the

buildup of neuritic plaques (Abate et al. 2017). These

deposits disrupt synaptic function and induce

oxidative stress and inflammation. Aβ peptides are

generated when amyloid precursor protein (APP) is

cleaved. As these peptides aggregate, they form toxic

oligomers that interfere with neuronal

communication (Huat et al. 2019). This

accumulation, particularly in the hippocampus and

cortex, accelerates neurodegeneration and promotes

the formation of tau tangles. As Aβ levels rise, it

triggers cellular dysfunction, oxidative stress, and

inflammation in the brain, all of which disrupt normal

neural activity and contribute to the progression of

dementia.

2.2 Hyperphosphorylation

In Alzheimer’s disease, tau hyperphosphorylation

occurs due to an imbalance between kinase and

phosphatase activities. Aβ aggregates can accelerate

the activity of multiple kinases, such as GSK-3β and

MAPKs, and stimulate caspase-3 and calpain-1.

These enzymes produce small fragments that lead to

neuronal death and neurite degeneration. Tau protein

contributes to memory loss by damaging

microtubules and disrupting cellular functions. The

process of tau hyperphosphorylation transforms the

protein from a monomer to an oligomer, which is

considered the most toxic form. This form induces

cellular impairment and results in the formation of

neurofibrillary tangles (NFTs), which are toxic

aggregates. Consequently, neurotransmitters and

neuronal signals are inhibited by the presence of

NFTs (Kabir 2019).

2.3 Metal-Dependent Toxicity

Several studies have shown that metal ions are related

to the progression of Alzheimer’s disease by

accelerating the accumulation of amyloid and tau

proteins. The increased levels of metals, including

copper, zinc, iron, and aluminum, in the brains of AD

patients, caused by impaired metal homeostasis, have

a strong affinity for tau protein and Aβ peptides,

increasing toxicity. The formation of Aβ-copper

complexes in the brain contributes to oxidative stress,

leading to the production of reactive oxygen species

(ROS) and significant neuronal damage. This

oxidative stress is associated with disturbances in

Phytochemicals in Alzheimer’s Prevention: Causes and Potentials

metal ion homeostasis and is commonly observed in

Alzheimer’s disease. It contributes to harmful

processes such as tau hyperphosphorylation, Aβ

deposition, cross-linking of nerve fibers, and nerve

cell damage, all of which are linked to the progression

of AD (Breijyeh & Karaman 2020).

2.4 Oxidative Stress and Mitochondrial

Dysfunction

Oxidative stress (OS) and mitochondrial dysfunction

are key indicators of Alzheimer’s disease. Elevated

levels of reactive oxygen species (ROS) and reactive

nitrogen species (RNS) induce lipid peroxidation,

protein degradation, and DNA damage in neurons,

exacerbating cellular injury. ROS, such as hydrogen

peroxide and hydroxyl radicals, can lead to brain

abnormalities and impair mitochondrial function,

contributing to the progression of aging and AD.

Moreover, neurons are particularly vulnerable to

oxidative stress because of high polyunsaturated fatty

acid content and low antioxidant levels (Lee et al.

2018). With advancing age, oxidative damage

disrupts synaptic function and neuronal

communication, which is associated with the

development of AD. ROS can also compromise the

blood-brain barrier (BBB), increasing its

permeability and allowing harmful substances to

enter the brain.

3 FACTORS CONTRIBUTE TO

ALZHEIMER’S DISEASE

Alzheimer’s disease is influenced by a multitude of

risk factors, including age, gender, alcohol

consumption, depression, high blood pressure, sleep

apnea, diabetes, obesity, smoking, mitochondrial

DNA, air pollution, free radicals, exposure to metals,

and neuronal damage, among others (Li et al. 2016,

Naik 2025). The following paragraphs delve into

several of these risk factors.

3.1 Aging

Aging is the primary risk factor for Alzheimer’s

disease (AD), as many pathological changes in AD

resemble those in normal aging. Most AD cases occur

after age 60, characterized by brain volume reduction,

synapse loss, amyloid-beta (Aβ) deposition, and

neurofibrillary tangles (NFTs). Two additional aging

processes impact AD: the breakdown of myelin and

damage to locus coeruleus (LC) cells. This damage

induces microglia to reduce Aβ clearance and

transmits noradrenaline through terminal varicosities

to the cortex (Nogales 2000). Vascular factors also

contribute to Alzheimer’s disease, and the blood-

brain barrier (BBB) may deteriorate with aging due to

cell death in the LC. Furthermore, decreased glucose

metabolism, mitochondrial dysfunction,

psychological abnormalities, and memory loss all

develop during the normal aging process, making it

difficult to distinguish early cases of Alzheimer’s

disease from normal aging (Grudzien et al.2007, Hou

et al.2019).

3.2 Environment

Environmental factors, including air pollution, diet,

and mineral imbalances, contribute to Alzheimer’s

disease (AD) by triggering oxidative stress and

neuroinflammation.

3.2.1 Air Pollution

Air pollution, which results from the introduction of

physical, chemical, or biological contaminants into

the atmosphere increases the risk of asthma,

cardiovascular disease, and Alzheimer’s disease. In

the United States, pollutants such as ozone, carbon

monoxide, nitrogen oxides, particulate matter,

sulfate, and lead are known to pose significant health

risks. Prolonged exposure to high levels of air

pollution not only affects the frontal brain region but

also damages the mucosal lining of the olfactory tract

and bulb. In individuals exposed to air pollutants, a

correlation exists between chronic oxidative stress,

neuroinflammation, and neurotoxicity. This link is

characterized by increased levels of phosphorylated

tau and amyloid-beta (Aβ) plaques in the cortex of the

frontal lobe (Nogales 2000).

3.2.2 Diet

The role of diet in Alzheimer’s disease (AD) has

recently attracted significant attention. While a high

intake of saturated fats and excess calories is

associated with an increased risk of AD, some

research suggests that certain dietary components—

such as antioxidants, vitamins, polyphenols, and

fish—may help reduce this risk. Food processing can

lead to the breakdown of heat-sensitive

micronutrients, significant water loss, and the

formation of harmful compounds (AGEs). Aging-

related enzymes are hazardous as they disrupt the

structure and function of cell receptors and amino

BEFS 2025 - International Conference on Biomedical Engineering and Food Science

acids, hence intensifying oxidative damage and

neuroinflammation. Elevated blood levels of AGEs

have been linked to cognitive decline and the

development of Alzheimer’s disease (Abate et al.

2017). Dietary deficiencies are also a significant

factor in Alzheimer’s disease. Insufficient levels of

folic acid, vitamin B12, and vitamin D—which

functions as an antioxidant—can contribute to

cognitive impairment and dementia. Additionally,

individuals with Alzheimer’s disease often

experience difficulties with swallowing and nutrient

absorption, which can further worsen their nutritional

status.

3.2.3 Metals

Metals can be classified as bio-metals (e.g., zinc,

copper, iron) essential for biological functions, or

hazardous metals (e.g., mercury, lead) harmful to

health. Aluminum exposure deserves special

attention. This metal, widely used in food packaging,

cosmetics, and medical devices, can enter the

bloodstream and bind to transferrin proteins and

nitrate compounds. This binding facilitates

aluminum’s transport to the brain. Research confirms

its accumulation in three critical brain regions: the

cortex, hippocampus, and cerebellum. It disrupts

normal protein structures, causing them to misfold,

and triggers abnormal phosphorylation of tau

proteins. Lead poses another threat through

competition with essential metals. It mimics calcium

and occupies binding sites in biological systems.

More alarmingly, lead can easily cross the blood-

brain barrier (BBB), the brain’s protective shield.

Once inside, it impairs two key neural processes:

nerve cell differentiation and synaptogenesis. Studies

have directly linked lead exposure to the development

of AD, showing increased β-secretase production and

accelerated amyloid-beta (Aβ) accumulation. These

findings establish toxic metals as significant drivers

of Alzheimer’s disease progression (Huat et al. 2019).

3.2.4 Infections

In the central nervous system (CNS), persistent

infections may contribute to the accumulation of Aβ

plaques and neurofibrillary tangles (NFTs). Dr. Ruth

Itzhaki indicates that individuals carrying the ApoE-

ε4 gene often harbor DNA from the herpes simplex

virus (HSV-1) in their brains. When HSV-1

proliferates in brain tissue, it triggers two primary

issues: First, it induces inflammation. Second, it

accelerates the aggregation of Aβ proteins. Both

effects damage nerve cells and may precipitate the

onset of AD. Other researchers have identified

bacterial infections as contributing factors as well.

For instance, the syphilis-causing bacterium

Treponema pallidum induces brain damage

resembling neurofibrillary tangles (NFTs). Another

example is Chlamydia pneumoniae which activates

two harmful cell types: astrocytes and cytotoxic

microglia. This activation disrupts the brain's calcium

balance regulation and interferes with normal cell

death processes (Breijyeh & Karaman 2020).

3.3 Medical Factors

Medical factors such as cardiovascular diseases

(CVDs) and metabolic disorders, particularly obesity

and diabetes, are significant contributors to the

development and progression of Alzheimer’s disease

(AD).

3.3.1 Cardiovascular Disease

Cardiovascular diseases (CVDs) significantly elevate

the risk of Alzheimer’s disease. Strokes directly

damage brain tissue, accelerating the accumulation of

amyloid plaques and tau tangles. Atrial fibrillation

generates blood clots that can obstruct cerebral

vessels, impairing memory networks. In heart failure,

weakened blood pumping leads to chronic brain

hypoperfusion, causing neuronal oxygen deprivation.

Hypertension induces arterial thickening, reducing

blood flow and potentially causing cerebral edema.

Most importantly, these vascular abnormalities also

disrupt amyloid clearance mechanisms. Therefore,

targeting CVD management could provide protection

against both cardiovascular and neurological

deterioration (Santos et al. 2017).

3.3.1 Obesity and Diabetes

Obesity, defined as excessive body fat accumulation

(BMI ≥ 30), disrupts brain function through

interconnected metabolic processes. Excess fat

reduces cerebral blood flow, increasing the risk of

stroke-related memory loss and vascular dementia.

Recently, it has been shown that obesity often leads

to elevated blood sugar levels due to impaired glucose

metabolism. Over time, this condition damages blood

vessels and promotes amyloid plaque accumulation

through three key mechanisms: oxidative stress,

mitochondrial dysfunction, and chronic brain

inflammation. Adipose tissue releases inflammatory

signals that overactive immune cells, triggering

systemic inflammation. This inflammation reduces

Phytochemicals in Alzheimer’s Prevention: Causes and Potentials

insulin sensitivity, creating a vicious cycle where

elevated blood sugar further exacerbates fat

accumulation. Importantly, obesity-related

inflammation directly impacts brain cells. Overactive

microglia—the brain’s immune cells—interfere with

insulin signaling by disrupting IRS-1 proteins, which

are crucial for neuronal survival (Lee et al. 2018).

4 ROLE OF PHYTOCHEMICALS

IN THE PREVENTION OF AD

Currently, available methods for preventing and

treating Alzheimer’s disease (AD), such as synthetic

medications, are only effective for a short period.

However, phytochemicals that are safe and

reasonably priced have shown encouraging potential

for their use in AD. In China, traditional Chinese

medicine (TCM) has demonstrated unique

therapeutic advantages in AD prevention due to its

diverse components, multi-target approach, and

holistic nature. Concurrently, patients with AD in

China have begun to incorporate medicinal plants and

herbal formulations into their preventive and

treatment regimens (Li et al. 2016). Phytochemicals

protect against both internal stressors (free radicals,

ROS) and external challenges (UV radiation,

predators, and pathogens) (Gao et al. 2020). Since

oxidative stress is a key contributor to AD, plants rich

in antioxidants can help mitigate its harmful effects.

To name just a few, coffee, blueberries, garlic, apples,

green tea, olives, golden root, fennel, sage, coconut,

walnuts, figs, pumpkin, spinach, and ginger have

shown efficacy in managing AD progression. While

the exact mechanisms vary, animal studies have

consistently shown three benefits: (1) blocking

amyloid clumping through enhanced α-secretase

activity, (2) slowing tau protein damage by 40-60%

in mouse models, and (3) improving maze navigation

speed by 18% in aged rats. However, real-world

effectiveness faces two significant obstacles: less

than 5% of ingested phytochemical compounds reach

the brain, and optimal doses vary widely—from 50

mg/day for curcumin to 500 mg/day for resveratrol.

Despite these challenges, this multi-target approach,

which simultaneously addresses protein misfolding

and inflammation, could reshape preventive

strategies for Alzheimer’s disease (Gao et al. 2020).

4.1 Polyphenolic Compounds

Polyphenols, which are widely found in grapes,

Salvia miltiorrhiza, tea, Gastrodia elata, and other

medicinal plants, have antitumor, antioxidant, anti-

inflammatory, and anti-oxidative stress properties, all

of which demonstrate the potential of these

compounds to combat Alzheimer’s disease (AD). For

example, proanthocyanidins—compounds found in

red wine and cocoa—exhibit three biological actions:

counteracting inflammatory pathways, enhancing

cellular insulin responsiveness, and scavenging

harmful free radicals. These effects have been shown

to decelerate pathological markers in transgenic AD

mice (Naik 2025). Resveratrol's therapeutic profile

stands out due to its ability to cross the blood-brain

barrier and directly inhibit the formation of amyloid

precursor protein. Additionally, its impact on gut

microbial populations provides another layer of

protection (Xu 2023). Similarly, gastrodin regulates

the gut-brain axis by preserving intestinal epithelial

tight junctions, reducing systemic endotoxin leakage,

and lowering neuroinflammation. Pterostilbene

highlights its mitochondrial stabilizing properties,

which inhibit the pathways of programmed cell death

typical of AD development. Meanwhile, ferulic acid

simultaneously promotes amyloid-beta clearance and

inhibits tau phosphorylation, though its precise

mechanism remains unclear (Sun et al. 2021). The

spectrum of polyphenolic compounds continues to

expand. While curcumin's efficacy depends on its

formulation due to absorption issues, salidroside's

cognitive improvement is associated with amyloid-

beta phagocytosis. This mechanistic diversity helps

scientists develop specific combinatorial treatments

targeting different AD subtypes.

4.2 Flavonoids

Flavonoids, plant-based compounds, show promise

for treating Alzheimer’s disease (AD) by targeting

key processes like oxidative stress,

neuroinflammation, and protein aggregation. Rose

flavonoids, in particular, have shown potential in

combating AD, especially when circadian rhythms

are disrupted. Studies indicate they reduce

inflammation and support neuroprotective proteins

like GRIN2B.

4.2.1 Flavonoid Compounds

Flavonoids are natural molecules present in plants

that show potential for treating Alzheimer’s disease

BEFS 2025 - International Conference on Biomedical Engineering and Food Science

(AD). For instance, Nobiletin and Luteolin can slow

down AD-induced damage by decreasing oxidative

stress and enhancing mitochondrial function. They

also reduce neuroinflammation, a major determinant

of the disease's progression. Rutin stands out for its

ability to inhibit tau protein aggregation and protect

against its detrimental effects (Sun 2021). Recent

studies have also shown that flavonoids can alleviate

endoplasmic reticulum stress, a condition linked to

memory loss in AD. These compounds appear to

rejuvenate neurons, thereby improving memory and

cognitive function (Gao 2022). Additionally, the gut-

brain axis is emerging as an important therapeutic

target. Quercetin-3-O-Glucuronide, for example,

helps modulate gut microbiota and reduce brain

inflammation by regulating short-chain fatty acids.

This effect has been confirmed in both gut studies and

cerebrospinal fluid analyses. Another flavonoid, like

Amentoflavone, exerts its effects by activating the

AMPK/GSK-3β pathway, which reduces

inflammation and prevents amyloid-beta

accumulation, thereby improving memory (Minocha

2022). Trilobatin reduces cognitive deficits, clears

amyloid plaques, and inhibits tau protein

accumulation by regulating the TLR4-MYD88-NF-

κB pathway. In conclusion, flavonoids target several

key processes in AD, including amyloid

accumulation, tau protein changes, and inflammation,

offering broader benefits than traditional treatments

that focus on a single aspect of the condition.

4.2.2 Rose Flavonoids

Rose flavonoids show potential in preventing

neurodegenerative diseases, particularly Alzheimer’s

disease (AD) linked to circadian rhythm disruption.

In recent years, increasing work and study pressures

have led to late-night activities and sleeplessness

across various age groups, from teenagers to middle-

aged individuals. Chronic disruption of circadian

rhythms may accelerate AD development. Previous

research using an AD mouse model demonstrated that

rose flavonoids have a significant inhibitory effect on

AD. By targeting neuronal cells and microglia,

researchers replicate an in vitro AD model, identify

specific genes and metabolites, and analyze protein

expression levels and signaling pathways. This

suggests that rose flavonoids could serve as a dietary

intervention to slow AD progression in individuals

with circadian rhythm disturbances (Li 2023). The

study focused on extracting rose flavonoids from

fresh roses. Researchers processed rose petals by

washing, dehydrating, and crushing them, followed

by extraction in a water bath with distilled water.

After centrifugation, the supernatant's flavonoid

concentration was measured to determine the total

flavonoid content. Researchers constructed an AD

cellular model by exposing PC12 and N2a cells to

Aβ42 for 24 hours to induce damage, simulating

Alzheimer’s disease. Elevated levels of inflammatory

markers, including NF-κB, TNF-α, and IL-1β,

confirmed the successful establishment of the AD

model. However, rose flavonoids significantly

diminished these inflammatory components,

suggesting their potential to reduce brain

inflammation associated with AD. Transcriptomic

analysis of Aβ42-exposed PC12 cells further revealed

that rose flavonoids enhanced grin2b activity, a key

gene in reducing inflammation and oxidative damage,

suggesting their role in AD prevention.

The next phase analyzed protein expression in

Aβ42-exposed cells treated with rose flavonoids

using Western blot technique. Researchers measured

GRIN2B and inflammatory markers (NF-κB, TNF-α,

and IL-1β), relative to the control protein β-actin. The

cells from the damage model were collected, lysed,

and analyzed for the expression of key proteins. The

results show that the Aβ42-treated group expressed

these inflammatory markers far higher than the

control group, whereas rose flavonoids markedly

reduced them, reinforcing their anti-inflammatory

potential in AD pathology. An overexpression study

was conducted, to explore the neuroprotective role of

GRIN2B. Considering that GRIN2B is a membrane

protein, expression strategies for both mammalian

and insect cells were evaluated. Functional proteins

are generated and transformed into DH5α-competent

cells by vector cloning. Plasmids from positive clones

were extracted, sequenced, and purified before

removing the protein for further analysis. Finally,

they docked all molecules using 7KL0 as a template,

established the molecular binding pockets, and

identified the most plausible ones. Molecular

dynamics studies showed that six main rose

flavonoids interacted significantly with the GRIN2B

protein, exhibiting varying affinities and stabilizing

each other, further supporting their potential role in

neuroprotection.

4.3 Alkaloids

Alkaloids, nitrogen-containing compounds from

medicinal plants, protect against Alzheimer’s disease

(AD) by reducing inflammation, oxidative damage,

and neuronal death. Matrine, from Sophora

flavescens plant, can help address memory loss by

Phytochemicals in Alzheimer’s Prevention: Causes and Potentials

decreasing proteins that trigger brain inflammation

and inhibiting the formation of amyloid-beta plaques.

This occurs through interference with the RAGE

pathway. Oxymatrine regulates the NF-κB pathway,

which is responsible for inflammatory responses, and

the MAPK pathway, which is involved in cellular

stress reactions. This suggests their potential for AD

treatment. Isorhynchophylline reduces amyloid-beta

deposition, excessive tau phosphorylation, and

neuroinflammation. Berberine, from Rhizoma

coptidis, can diminish the accumulation of amyloid-

beta deposits, excessive tau protein phosphorylation,

and neuronal loss. Palmatine enhances cognitive

performance and restores mitochondrial health,

suggesting its potential to prevent Alzheimer’s

disease (Li 2023).

4.4 Terpenes

Terpenoids, found in medicinal plants, possess

unique biological properties, including anti-

inflammatory, anti-oxidant, and anti-apoptotic

characteristics. These properties endow terpenoids

with both preventive and therapeutic effects on

Alzheimer’s disease. For example, Huperzine-A,

derived from the plant Huperzia serrata, protects

brain cells by reducing the accumulation of Aβ

proteins, supporting proper mitochondrial function,

and maintaining balanced cellular iron levels (Friedli

& Inestrosa 2021). Additionally, Paeoniflorin,

prevents neuronal death via ferroptosis, mediated by

the P53 pathway. Geniposidic acid improves

cognitive performance, reduces Aβ accumulation,

and decreases neuronal death and neuroinflammation.

Ginkgolide B, from ginkgo biloba leaves, reduces the

expression of the inflammasome NLRP3 and

improves memory and cognitive functions. Patchouli

oil suppresses Aβ plaque accumulation, excessive tau

protein phosphorylation, neuroinflammation, and

intestinal dysbiosis. By facilitating Aβ transport and

reducing oxidative damage, neuroinflammation, and

tau protein phosphorylation, these compounds

provide defense against Alzheimer’s disease.

4.5 Polysaccharides

Plant-based polysaccharides have gained global

attention for their antioxidant, anti-inflammatory, and

oxidative stress-resistant properties, which are

closely linked to Alzheimer’s disease (AD). These

polysaccharides mitigate AD risk factors by

enhancing neuroplasticity, stimulating neuronal

growth, restoring neurotransmission, and reducing

neuroinflammation. For example, angelica

polysaccharides can improve memory impairment by

reducing oxidative damage, inflammation, and

apoptotic cell death. Polysaccharides derived from

Chinese Coptis species protect against Aβ-induced

neurodegeneration, reduce phosphorylated tau

accumulation, and alleviate oxidative stress.

Polysaccharides from Lycium barbarum reduce Aβ

plaque accumulation and improve cognitive function.

In animal models induced with D-galactose,

polysaccharides from Polygonatum sibiricum exhibit

potent anti-inflammatory and antioxidant properties

(Bian et al. 2022). Additionally, polysaccharides from

Cistanche deserticola can enhance cognitive abilities

by restoring equilibrium in the gut microbiota-brain

axis.

5 RECENT STATUS OF

PHYTOCHEMICALS IN AD

PREVENTION ACROSS

DIFFERENT REGIONS

Plant-derived bioactive compounds have been used

for millennia, especially in China and other Asian

countries like Korea, Japan, and Taiwan. The Chinese

have accumulated extensive clinical experience in

using phytochemicals to prevent neurodegenerative

diseases, with herbal products accounting for

approximately 40% of the pharmaceutical market

(Naik 2025). Globally, the WHO (World Health

Organization) reports that roughly 85% of the

population relies on medicinal plants for healthcare.

5.1 Global Examples

Traditional medicine worldwide utilizes various

plants to combat Alzheimer’s disease (AD) in India,

plants like Evalvulus alsinoides and Myristica

fragrans inhibit acetylcholinesterase, enhancing

cognitive function. In Europe, ethanolic extracts from

medicinal herbs block acetylcholinesterase and

amyloidogenic processes. Medicinal plants from the

Australian rainforest reduce neuroinflammation. In

West Africa, approximately 10,000 medicinal plants

are used to treat neurological disorders, including

Phyllanthus amarus, Rauwolfia vomitoria, and Abrus

precatorius. In Japan, a traditional Kampo formula

known as ninjin'yoeito (NYT) has been shown to

benefit Alzheimer’s disease (AD) patients

experiencing symptoms of depression and cognitive

impairment. Similarly, Ginkgo biloba extract, widely

BEFS 2025 - International Conference on Biomedical Engineering and Food Science

recognized as a treatment for AD, is extensively used

in Western countries. Additionally, galantamine, a

selective reversible acetylcholinesterase inhibitor,

has been approved for use in several countries,

including the United States and Germany. Moreover,

the U.S. Food and Drug Administration (FDA) has

approved drugs such as donepezil, memantine, and

rivastigmine for AD treatment (Varadharajan 2023).

Plant-based medicinal compounds have shown

significant potential in slowing the progression of

Alzheimer’s disease and alleviating symptoms.

5.2 Traditional Chinese Medicine

Development in AD

Driven by government policies and collaborative

research, Traditional Chinese Medicine (TCM) has

emerged as a promising approach to Alzheimer’s

disease (AD) therapy in China. AD is a priority in

China's 14th Five-Year Plan for TCM development,

with studies funded by the National Natural Science

Foundation of China (NSFC). Recent advancements

highlight the potential of classic TCM formulas and

single herbal ingredients. Key advancements include

Huperzine A, a cholinesterase inhibitor that reduces

AB plaques and enhances cognitive function, now in

Phase III trials, and ginsenoside Rg1, which promotes

autophagy to clear AB accumulation (Ma 2023).

Traditional TCM formulas such as Huanglian Jiedu

Decoction and Liuwei Dihuang Pill have been re-

engineered using artificial intelligence and network

pharmacology to elucidate their multi-target

mechanisms, including NLRP3 inflammasome

inhibition and regulation of the "kidney essence-brain

axis." The Compound Sea Snake Capsule, the first

TCM-approved medicine for AD, has demonstrated

effective collaboration between policy and industry,

showing a reduction in Aβ and Tau pathology in

multicenter trials. Despite these advancements,

challenges remain. Quality control of complex TCM

formulas is inconsistent, and there is a lack of high-

level evidence, such as long-term randomized

controlled trials (RCTs). To address these issues,

China is leveraging AI-driven medicine screening

and forging international partnerships. For instance,

the FDA granted orphan drug designation for

Compound Danshen Dripping Pill in 2022,

highlighting the growing global impact of TCM in

AD therapeutics.

6 POTENTIALS AND

CHALLENGES

Alzheimer’s disease is a complex neurodegenerative

condition influenced by multiple risk factors. With

the rising incidence rate, it is highly important to

identify the real problems and develop innovative

ideas for both therapy and prevention. Recent

discoveries highlight the pivotal role of

phytochemicals in preventing and treating

Alzheimer’s disease. The use of plant-based

alternatives offers a novel approach to Alzheimer’s

disease treatment, enabling millions of patients to

overcome their unpleasant symptoms.

Phytochemicals reduce the synthesis and

accumulation of pathogenic proteins, enhance

cognitive function, mitigate oxidative and

inflammatory stress, and regulate mitochondrial

activity. Many studies conducted over the years have

shown that phytochemicals are quite effective in

lowering the risk of Alzheimer’s disease.

Additionally, phytochemicals have shown promise in

fighting several viral infections, such as Ebola,

Hepatitis, and COVID-19 by reducing viral DNA

replication and limiting systemic invasion. To explore

the potential of phytochemicals in stopping epidemic

viruses, researchers need to create a precise

understanding of the mechanisms and activities of

various components, guiding them to design therapies

and treatments for combating diseases.

However, despite their promise in alleviating and

mediating AD symptoms, several challenges need to

be considered. These include safety issues, extraction

methods, dosage, combination, and efficacy.

Therefore, rigorous clinical trials are essential to

guarantee their safety and efficacy. Questions also

persist regarding the integration of phytochemicals

and Traditional Chinese Medicine (TCM) in AD

treatment. Advanced research techniques—such as

network pharmacology, metabolomics, and gut

microbiome analysis — are needed to clarify their

physiological roles and mechanisms. Medicinal

plant-based molecules face several challenges in

practical application, including unstable chemical

structures, limited bioavailability, and sensitivity to

oxidation. Fortunately, techniques such as liposome

encapsulation or nanoparticle formulations may help

overcome these constraints. Furthermore, many

bioactive substances derived from plants struggle to

cross the blood-brain barrier (BBB) and reach the

brain. Notably, modulating gut microbiota via the

"gut-brain axis" presents a promising strategy for AD

Phytochemicals in Alzheimer’s Prevention: Causes and Potentials

prevention (Chen 2025). In conclusion, while

challenges exist, medicinal plants offer significant

potential in neurodegenerative disease treatment.

With large-scale studies and clinical trials,

phytochemicals have the potential to offer safe and

effective therapeutic options for Alzheimer’s disease.

7 CONCLUSION

Alzheimer’s disease is the most common and

demanding neurological disorder worldwide. While

contemporary pharmaceutical treatments have

evolved, phytochemicals from medicinal plants have

shown promise in targeting key AD mechanisms,

including amyloid-beta accumulation,

neuroinflammation, and tau hyperphosphorylation.

Because of their neuroprotective properties,

phytochemicals offer a safe, cost-effective, and

promising alternative to modern drugs. Flavonoid

compounds, particularly rose flavonoids, stand out

among other phytochemicals in their ability to

mitigate oxidative stress and inflammation, reducing

the risk of AD caused by disturbance of circadian

rhythm These compounds increase the action of

antioxidant enzymes and reduce the synthesis of

harmful pro-inflammatory cytokines, protecting

neurons from damage. The diverse mechanisms make

them promising candidates for both therapy and

prevention of Alzheimer’s disease. Various countries

use different approaches to phytochemical research.

Traditional Chinese medicine (TCM) integrates

modern scientific techniques with traditional

methods. Traditional medicinal herbs are extensively

used for AD treatment in India and Japan, developed

in national research projects and clinical trials.

Western nations, on the other hand, focused more on

particular phytochemicals. Regardless of these

differences, there is a worldwide agreement that

phytochemicals have great potential for AD

treatment, and cooperation between countries is

necessary to speed up studies and handle problems.

Still, challenges remain, including inadequate brain

penetration, variable bioavailability, and insufficient

clinical data. Fortunately, emerging solutions, such as

liposome encapsulation, nanoparticles, and network

pharmacology, are improving efficacy. Additionally,

advancements in multi-omics and gut-brain axis

research are expanding the role of phytochemicals in

AD prevention and therapy. In conclusion,

phytochemicals represent a unique frontline in the

fight against Alzheimer’s disease, supported by

evidence of the efficacy of medicinal plants and their

long-standing history in traditional medical systems.

Unlocking the full potential of these natural

compounds will depend on ongoing research, large-

scale clinical trials, and the application of modern

scientific technologies.

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