Beneficial (and some negative) Plant/Natural Chemicals

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Introduction to plants and their chemicals

The expression, “Let Food be Thy Medicine” is a famous quote by the Greek physician Hippocrates (c. 460 – c. 370 BC). But which foods?

Dr Mark Hyman is an American physician and author. He is is the director of Cleveland Clinic Center for Functional Medicine.

Plants and their compounds can certainly have beneficial effects. Herbs and herbal remedies have been used for thousands of years in traditional medicine for various conditions in a safe and effective manner. Some of the qualities being anti-inflammatory, anti-carcinogenic, anti-atherosclerotic, antibacterial, antimitotic, anti-inflammatory, analgesic, local anesthetic, hypnotic, psychotropic, and antitumor activity, antifungal antibacterial, antiviral, cholesterol-lowering inflammatory, antihypertensive, vasodilator effects, antiobesity, antihypercholesterolemic and antiatherosclerotic activities.

But just because something comes from a plant, doesn’t automatically mean it’s good for you. Depending on the particular compound, it can be beneficial, neutral, or negative. Some plant chemicals are beneficial unless you ingest too much. Some have beneficial and detrimental chemicals in the same plant.

And if that’s not confusing enough, the terms used: polyphenol, resveratrol, flavonoid, lectin, oxalates, etc. can make a head spin!

Neuroprotective effects from natural products. Source: Neuroprotective Natural Products for Alzheimer’s Disease (Xin Chen et al, 25 May 2021)

Vegetables do often contain toxins and anti-nutrients that interfere with the absorption of nutrients. The toxins are natural defenses that the plant uses to ward off the insects, predators, and fungi that might attack it. These include such things as trypsin inhibitors and lectins, which include wheat germ agglutinin found in whole wheat products (mimics insulin). Additional negative components include gluten (contributes to leaky gut, no celiac disease required) and oxalates (inflammation). All of those are discussed in greater detail in the terms section. Fortunately, many (not all) toxins can be deactivated with proper cooking methods, such as soaking and pressure cooking.

Fructose is a sugar that can have harmful effects. It is found naturally in sources such as ripe fruit and honey. It is also found in high fructose corn syrup (HFCS), a combination of fructose and glucose, and table sugar (sucrose) also a combination of fructose and glucose. Regardless of source, fructose sends information to the body that times of scarcity are coming. These signals result in physiological changes that were helpful for early human survival, but overstimulation of these adaptations today results in negative health issues. Complicating this, reducing fructose levels in the body is not as simple as avoiding fructose consumption. Under certain circumstances, many of which come from the western diet, the body produces its own (endogenous) fructose, without consuming (exogenous) fructose. Since these damaging effects come from more than just consumption from plants, this subject warrants its own wiki article, see From Fructose to Alzheimer's.

Additionally, new world fruits and vegetables have posed a very recent introduction to the vast majority of world population, that is except for the native Americans. Until the explorers introduced them, no European, African or Asian had ever been exposed to them, which means, their body, gut bacteria, and immune system were ill-prepared to tolerate them, although the response from the body is often subtle to imperceptible. Such negative (albeit subtle to imperceptible) responses often extend to this date as this introduction happened 500 years ago, which put into perspective is trifling in comparison to the entire human evolution timeline, suggesting we still haven’t adjusted to them. New world fruits and vegetables include foods from the bean family (legumes, peanuts, cashews), grains, pseudo-grains such as amaranth and quinoa, the squash family (pumpkins, acorn squash, zucchini) as well as chia and certain seeds.

But especially for APOE4s, there are beneficial compounds that come from plants. Certain phytochemicals have antioxidant, anti-inflammatory, anti-amyloid, and anticholinesterase properties - the four fundamental pillars identified in the process of Alzheimer’s.

Phytochemicals can offer neuroprotective effects which not only act at the level of blocking the progression of Alzheimer’s but also aid in Alzheimer’s prevention. By incorporating natural compounds with other therapeutic interventions, the onset or progression of Alzheimer’s could be dramatically reduced, counteracting the estimate that the number of people with dementia will nearly triple to more than 152 million by 2050. [Source: Global dementia cases forecasted to triple by 2050 (Alzheimer's Association, 27 Jul 2021)]

This is not a comprehensive article but an attempt to condense and simplify the subject of phytochemicals with emphasis on Alzheimer’s Disease.

Neuroprotective effects from natural products. Source: Figure 1 Neuroprotective Natural Products for Alzheimer’s Disease (Xin Chen et al, 25 May 2021)


Polyphenols are a group of compounds found in plant foods that are beneficial for health. Polyphenols are how fruits, berries, and vegetables get their vibrant colors and determines their taste and aroma. Over 8,000 polyphenols have been discovered. They're naturally found in many plant-based foods like fruits, vegetables, herbs, tea, red wine, and dark chocolate. Most of the health benefits of polyphenols relate to their role as an antioxidant.

Through the antioxidant property, they help protect the body and neutralize free radicals that cause damage to cells. Free radicals are highly reactive oxygen molecules produced by normal cell processes and external factors like radiation, air pollution, smoking, and chemical exposure. Without antioxidants to neutralize free radicals, cells are injured increasing health problems.

Without antioxidants to neutralize free radicals, damaging oxidative stress occurs unleashing an inflammatory cascade thus increasing health problems.

Free radicals are highly reactive oxygen molecules produced by normal cell processes and external factors like radiation, air pollution, smoking, and chemical exposure. Without antioxidants to neutralize free radicals, cells are injured, increasing your risk of health problems like diabetes, heart disease, and cancer.

Antioxidants and polyphenols are often considered to be the same thing, but technically, it’s many of the polyphenols that contain antioxidants.

Researchers have identified the role polyphenols play in delaying the onset of dementia and reducing the risk for Alzheimer's. For example, resveratrol, found in grape skins and red wine, has been found to have neuroprotective effects. Other studies have demonstrated a reduction in the progression of dementia when polyphenols were included in the daily diet, through changes in the neurological system leading to dementia. Some of these papers can be found in the below section Deeper dive into the science of natural products and health effects

Among the many potential health benefits of polyphenols, those of interest to APOE4s include:

  • Lower Blood Sugar Levels
  • Increase Insulin Sensitivity
  • Reduce Inflammation
  • Improve Heart Health
  • Boost Brain Function

According to this clinical trial, The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial, increased polyphenol intake was inversely associated with biological againg. (Anat Yaskolka Meir et al, 25 Sept 2023) increased polyphenol intake is inversely associated with biological aging.

Why the name polyphenol? Polyphenols are characterized by the existence of more than one phenol unit — or building block — per molecule. That's what makes them poly- (many) phenols. There's another name for polyphenols — phenolics.

Want to know the polyphenol content of certain foods? Go to Phenol-explorer. At the writing of this wiki, Phenol-explorer is a database that contains more than 35,000 content values for 500 different polyphenols in over 400 foods. These data are derived from the systematic collection of more than 60,000 original content values found in more than 1,300 scientific publications. Each of these publications has been critically evaluated before inclusion in the database. The whole data on the polyphenol composition of foods is available for download.

Just one screen shot of the many ways to sort and view the database of foods and polyphenols from Phenol-explorer

The Phenol-explorer database is comprehensive and likely more information than most people need, so for a quick reference here’s a list of Polyphenol-Rich Foods. [Source: 64 Foods High in Polyphenols (Ashley Braun, 9 Feb 2022)

Vegetables high in polyphenols

  • Broccoli
  • Carrots
  • Spinach
  • Red lettuce
  • Onions
  • Asparagus
  • Artichokes
  • Shallots
  • Garlic

Fruits high in polyphenols (but watch the glycemic load)

  • Blueberries
  • Strawberries
  • Raspberries
  • Blackberries
  • Cranberries
  • Grapes
  • Cherries
  • Lemon
  • Grapefruit
  • Oranges
  • Pears
  • Apples
  • Peaches
  • Plums
  • Pomegranate
  • Nectarine
  • Apricots
  • Olives and olive oil

Nuts and Seeds high in polyphenols

  • Walnuts
  • Almonds
  • Flaxseed
  • Chia seeds
  • Pecans
  • Chestnuts
  • Hazelnuts

Herbs and Spices high in polyphenols

  • Turmeric
  • Cinnamon
  • Cumin
  • Cloves
  • Celery seed
  • Basil
  • Ginger
  • Marjoram
  • Parsley
  • Peppermint
  • Oregano
  • Rosemary
  • Sage
  • Thyme
  • Lemon verbena

Other foods and drinks high in polyphenols

  • Green tea
  • Black tea
  • Red wine
  • Dark chocolate
  • Cocoa powder
  • Coffee
  • Vinegar
Dr Terry Wahl's protocol emphasizes a varied balance of different fruits and vegetables, this helps maximize the types of beneficial polyphenols.

It's best to keep the types of polyphenols consumed varied. This aligns with the feeding habits of our hunter-gathers ancestors. “Ancient foragers regularly ate dozens of different foodstuffs. … This variety ensured that the ancient foragers received all the necessary nutrients.”[Source: the book, Sapiens: A Brief History of Humankind by Yuval Noah Harari, PhD, page 59, kindle location 854 of 7356].

Dr Teri Wahls, in her book, The Wahls Protocol, describes how she repaired her cells by following a diet similar to how our ancestors ate (Paleo). Among her recommendations, she recommends a varied balance of different types of vegetables and fruits daily, including greens (kale, collards, chard, lettuce-darker the better, etc), deeply colored (beets, carrots, etc.), and rich in sulfur (cauliflower, broccoli, cabbage, asparagus, brussel sprouts, turnips, radishes, onions, garlic, etc). For more information on Dr Wahl’s approach see ApoE4's wiki on Mitochondria. Also refer to the podcast with her, which includes show notes, Heal Neurodegeneration w/ Paleo Principles

Subcategories of Polyphenols

Polyphenols are divided into four main categories:

  • flavonoids
  • stilbenes
  • lignans
  • phenolic acids

Some of those categories can be broken down into additional subgroups.

The four main categories of polyphenols with a further breakdown of flavonoids


Flavonoids are a class of polyphenol rich in antioxidant activity. Flavonoids help regulate cellular activity and fight off the free radicals that cause oxidative stress on your body. Allergens, germs, toxins, and other irritants can trigger inflammation that results in uncomfortable symptoms. Flavonoids may help your body dismiss that inflammatory reaction so that those symptoms are reduced.

Flavonoids include: flavonols, flavones, flavanones, flavanols or flavan-3-ols, anthocyanins, and isoflavonoids.

Flavonols. Flavonols are the largest subclass of the flavonoids. Flavonols exist in many colors varying from white to yellow, and they are closely related in structure to the flavones. Flavonols are represented mainly by quercetin, kaempferol, and myricetin. Flavonols have many benefits to human health because they have antioxidant and neuroprotective properties in addition to their effects in prevention of atherosclerosis and other vascular diseases.

Flavones. Flavones are closely related in structure to the flavonols. Both in vitro and in vivo to have shown neuroprotective effects. Flavones are common in foods, mainly from spices, and some yellow or orange fruits and vegetables.

Flavanones. Flavanones are another important class which is generally present in all citrus fruits. Epidemiological studies reported an inverse relationship between their intake and the risk of cardiovascular diseases. Clinical and experimental data further showed their antihypertensive, lipid-lowering, insulin-sensitizing, antioxidative, and anti-inflammatory properties, which could explain their antiatherogenic action in animal models.

Sources with top flavanol levels

Flavanols. Flavanols or flavan-3-ols is a class of flavonoid. They represent the most common flavonoids consumed in the American diet. Tea, chocolate, grapes, apples, and red wine are some of the prominent sources of these polyphenols.

Anthocyanins. These flavonoids are water-soluble pigments. They are responsible for the colors, red, purple, and blue, are in fruits and vegetables. Berries, currants, grapes, and some tropical fruits have high anthocyanins content. Red to purplish blue-colored leafy vegetables, grains, roots, and tubers are the edible vegetables that contain a high level of anthocyanins. There are many different anthocyanins, with the six most common being: • Cyanidin • Delphinidin • Malvidin • Peonidin • Petunidin • Pelargonidin

Isoflavonoids. Isoflavonoids are structurally similar to estrogens, exerting both estrogenic and antiestrogenic properties in various tissues. Some studies support the notion of a protective effect of their consumption in immunomodulation, cognition, risk reduction of certain cancers, cardiovascular and skin diseases, osteoporosis and obesity, as well as relief of menopausal symptoms. [Source: Isoflavonoids – an overview of their biological activities and potential health benefits (Eva Miadoková, Dec 2009)


Abundant in grapes, berries, and conifer bark waste stilbenes, a diverse group of natural defense phenolics, may confer a protective effect against aging-related diseases.

Resveratrol is a well-known polyphenol which is found mainly in the skin of grapes; it has attracted extensive scientific attention due to its potential health benefits related with its cardiovascular (French paradox), chemopreventive, antiobesity, antidiabetic, and neuroprotective properties. However, recent data have highlighted that also other stilbene compounds such as pterostilbene may have higher bioavailability and possess better neuroprotective activity against AD than resveratrol. [Source: Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases (Mika Reinisalo et al, 9 Jun 2015)]


Lignans are a large group of low molecular weight polyphenols found in plants, particularly seeds, whole grains, and vegetables. The name derives from the Latin word for "wood". Lignans are precursors to phytoestrogens with weakly estrogenic and anti-estrogenic properties.

Health benefits attributed to lignans have included a lowered risk of heart disease, menopausal symptoms, osteoporosis and breast cancer.

The highest concentrations of dietary lignans are found in flaxseed.

Differences in bioavailability of various plant lignans from foods, and variation in enterolignan production among gut microbial communities contribute to large interindividual variation in enterolignan exposure. Consequently, studying associations between lignan exposure and health and disease in humans is challenging. Current evidence suggests a diet rich in lignans may be beneficial, but further research is needed to characterize the specific role of lignans.

Different applications of phenolic acids for health benefits. [Source: Figure 4 from Phenolic acids: Natural versatile molecules with promising therapeutic applications (Naresh Kumar and Nidhi Goel, 20 Aug 2019)]

Phenolic Acids

Phenolic acid accounts for about 30% of all known polyphenols. Phenolic acids are commonly found and well documented for health protective effects like antimicrobial, anticancer, anti-inflammatory, anti-mutagenic, and more. Phenolic acid is found in foods like grapes, berries, pomegranates, walnuts, chocolate, coffee, and green tea. The key advantage of using phenolic acids is their metabolizing ability by natural microbes; therefore provide an essential alternate to man-made chemicals which are harmful to environment also.

For more information on phenolic acids, see Phenolic acids: Natural versatile molecules with promising therapeutic applications(Naresh Kumar and Nidhi Goel, 20 Aug 2019)


Isothiocyanates are a very important group of biologically active compounds. Isothiocyanates are toxic defensive chemicals against invading organisms such as herbivores, insects, and microorganisms.

In organisms like humans, isothiocyanates are detoxified by conjugation with glutathione.

Isothiocyanates are mainly produced by cruciferous species. Numerous scientific studies have established that consumption of large amount of cabbages, broccoli, cauliflower, and brussels sprouts is associated with a decreased risk of carcinomas of the lung, stomach, colon, and rectum.

In cultured cells and animal models, isothiocyanates also exhibited antioxidant and anti-inflammatory activities.

For more information on isocyanates, visit Isothiocyanates


Alkaloids are produced by a large variety of organisms including bacteria, fungi, plants, and animals.

Medical use of alkaloid-containing plants has a long history. They have diverse physiological effects: antibacterial, antimitotic, anti-inflammatory, analgesic, local anesthetic, hypnotic, psychotropic, and antitumor activity and many others.

Most plants contain several alkaloids. Most of the known functions of alkaloids are related to protection. the presence of alkaloids in the plant prevents insects and animals from eating it. However, some animals are adapted to alkaloids and even use them in their own metabolism.

Such alkaloid-related substances as serotonin, dopamine and histamine are important neurotransmitters in animals.

The anticholinesterase activity of alkaloids, together with their structural diversity and physicochemical properties, makes them good candidate agents for the treatment of AD.

For greater investigation of this subject, see Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer's disease(Eduardo Luis Konrath et al, Dec 2013)


Cannabinoids interact with the body's cannabinoid receptors. There are numerous plant based cannabinoids mainly obtained from plants of the genus Cannabis.

Cannabinoids interact with the body’s endocannabinoid system (endo = internal). The endocannabinoid system (ECS) is responsible for a variety of physiological and cognitive processes. The body produces its own endocannabinoids.

Phytocannabinoids are cannabinoids obtained from plants, cannabis plants primarily. At least 85 different cannabinoids have been isolated from the cannabis plant. The two cannabinoids usually produced in greatest abundance are cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). THC is the cannabinoid that produces the "high" from consuming marijuana.

Cannabinoids interact with the body’s cannabinoid receptors to regulate a variety of functions in the body, such as inflammation, pain perception, mood, and memory.

Cannabis has been used as medicine for thousands of years, but experts are still trying to fully understand the endocannabinoid system. The efficacy of cannabinoids with Alzheimer’s or cognitive issues is not yet well elucidated.

For a deeper discussion, see Cannabinoids, Cannabidiol (CBD), THC, HEMP, Marijuana, Cannabis

Fungi (mushrooms)

Technically, mushrooms are not plants but fungi. Although not a plant, mushrooms are a natural product that can offer many brain boosting benefits, so they’ve been added here.

Mushrooms hold a wealth of brain-health promoting compounds. Source of graphic: Figure 2 from Unveiling the Therapeutic Potentials of Mushroom Bioactive Compounds in Alzheimer’s Disease (Na Li et al, 7 Aug 2023)

The medicinal properties of mushrooms have long been known to traditional medicine. In controlled studies mushrooms have been found to have anti-oxidant, anti-bacterial, and anti-viral properties. Immune-enhancing effects are present in nearly all mushrooms, including those commonly found in ordinary grocery stores. Mushrooms are also low calorie yet nutrient dense and aid in gut health to protect intestinal lining; a leaky gut can lead to a leaky brain barrier and increase neuroinflammation [for more info see Gut-Brain Connection: Leaky Gut/Leaky Brain, Microbiome (gut bugs)]

Bioactive compounds in mushrooms

According to Medicinal Mushrooms: A Clinical Guide (Martin Powell, 2014) there are about 14,000 species of mushrooms. About 5 percent are known to produce compounds with widespread physiological activity and therapeutic benefits. The medicinal properties and mechanisms of action come from these bioactive compounds that vary in content from one mushroom to another:

Beta-Glucans -- The most significant bioactive compound. These are polysaccharides characterized by their ability to modulate the immune system. Beta-glucans have anti-inflammatory, metabolic, and gastrointestinal effects.

Triterpenes -- These are a class of compounds that are responsible for mushrooms’ antiviral, anti-inflammatory, and even hypnotic properties. There are unique triterpenes, most notably the ganoderic acids in reishi mushrooms and the betulinic acid in chaga mushrooms. Research has uncovered more than 300 triterpenoids in reishi alone, many of which are not found in other mushroom species.

Sterols -- Mushrooms also produce sterols, principally ergosterol. Sterols work and act like cholesterol, but can lower cholesterol levels in the body. Additionally, ergosterol derivatives are reported to have anti-aging activity similar to resveratrol. Ergosterol is also a precursor to vitamin D, so when a mushroom is exposed to the sun for long periods, it increases the vitamin D content, which is why some vitamin D supplements are made from mushrooms.

Statins -- Researchers have discovered that some mushrooms can lower cholesterol because they possess statins such as lovastatin, which is used in cholesterol-reducing drugs. However, it’s important to note that high amounts of mushroom powder would be necessary to affect an impact.

Perhaps the best fungi for brain health are Lion’s Mane, Reishi, and Chaga mushrooms (marked with ★ below). They help protect the brain from neurodegeneration, boost cognitive function, improve memory, mood, focus and concentration, and support counteracting diseases such as Alzheimer's and dementia.


Chaga grows as a parasite on birch trees in cold climates. It has long been incorporated in folk medicine in China, Korea, Japan, and eastern Europe. Chaga Mushrooms hold one of the most potent antioxidants on the planet. It measures higher on the ORAC (oxygen radical absorbance capacity) than other well known antioxidant rich foods as the acai berry, baobab and turmeric root. Chaga has been shown to be protective against Alzheimer’s disease and neurodegeneration and inflammation by acting as an antioxidant and upregulating the Nrf2 pathway–one of the key anti inflammatory pathways in the body. The Chaga mushroom has also shown to inhibit apoptosis (programmed cell death). In animal studies chaga lowers blood sugar levels and reduces cholesterol. Chaga offers a range of helpful properties, including antitumor, anti-fatigue, antioxidant, antiviral and anti-inflammatory effects.


A nutrient-dense, low-calorie mushroom that provides several important vitamins and minerals, often rare in plant sources. Chanterelle mushrooms are an excellent source of polysaccharides like chitin and chitosan. These two compounds help to protect your cells from damage and stimulate your immune system to produce more cells. Chanterelle mushrooms are known to help reduce inflammation and lower the risk of developing certain cancers.


Cordyceps is a parasitic fungus that lives on certain caterpillars in the high mountain regions of China. Because of the location of where they’re found and the necessary harvesting method, natural forms can cost up to $63,000 a pound. Therefore, most cordyceps supplements are made in a lab. The antifungal peptide obtained from this mushroom, cordymin, holds anti-inflammatory properties and has a neuroprotective effect on an ischemic brain (restricted or reduced blood flow, thus oxygen). [Source: Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer’s disease and Alzheimer-linked pathologies: modulation by nutritional mushrooms(Angela Trovato Salinaro et al, 14 Feb 2018) Cordyceps might also improve immunity.

Cordyceps benefits include antitumor activity, immunomodulating effects, antioxidant activity, antihyperglycemic activity, sexual and reproductive function enhancement activity, antifatigue activity, protective effect on the kidney, effect on the liver. [Source: Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Chapter 5 Cordyceps as an Herbal Drug(Bao-qin Lin and Shao-ping Li, 2011)].


Cremini mushrooms (alternate spelling "crimini") are also known as baby bella mushrooms or brown mushrooms. Cremini are the same species of mushroom as white button mushrooms and Portobello mushrooms. Cremini have grown longer than white button mushrooms, thus they hold a more developed flavor but they are not as mature as Portobello mushrooms. Cremini mushrooms may potentially improve certain risk factors for type 2 diabetes, but there is limited evidence at present.

★Lion’s Mane

Lion's mane mushroom is also known as monkey head mushroom or bearded tooth mushroom. The hairy-looking mushroom is found in Asia, Europe and North America on decaying or dead trees. Among other medicinal mushrooms, this species has received particular attention for its potential neuroprotective properties.

Lion’s Mane mushrooms stimulate the release of nerve growth factor (NGF) and may promote neurite outgrowth. Low levels of NGF drives synaptic degeneration, amyloid-beta plaque formation and neural diseases (Alzheimer’s, Dementia and Parkinson’s Disease). NGF also promotes the repair and regeneration of damaged neurons and may reduce the risk for neurodegenerative disease and loss of brain function.

Lion’s mane contains an extraordinarily large quantity of structurally different bioactive and potentially bioactive components. The reported health-promoting properties of these compounds include anticarcinogenic, antibiotic, antidiabetic, antifatigue, antihypertensive, antihyperlipodemic, antisenescence, cardioprotective, nephroprotective, hepatoprotective, and neuroprotective properties and improvement of anxiety, depression and cognitive function. [Source: Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer’s disease and Alzheimer-linked pathologies: modulation by nutritional mushrooms(Angela Trovato Salinaro et al, 14 Feb 2018)


Oyster mushrooms are known for their impressive health-promoting properties and contain a variety of powerful compounds. They’ve been used in traditional medicine approaches for centuries

Highly nutritious, oyster mushroom may reduce heart disease risk factors like high blood pressure and cholesterol, may help regulate blood sugar levels, and supports the immune system.


Reishi offers a long list of potential benefits. It is known as the "Mushroom of Immortality" in Korea and China. In Chinese medicine, reishi is used to boost overall health and longevity.

Reishi has been shown to be neuroprotective, helps calm an overactive nervous system, supports the adrenals, reduces stress and anxiety, boosts antioxidants, lowers inflammation and may have anti-depressive effects. It helps boost brain health by decreasing the activation of pro-inflammatory pathways such as PGE2 and TNFa that are linked to neurodegenerative diseases and depression. Reishi has also shown to inhibit the creation of amyloid beta plaque. Studies performed on cells and animals have highlighted the possibility that compounds from this mushroom could slow the progression of Alzheimer's disease.


Shiitake protects against cell damage, helps your immune system with anti-inflammatory properties, and boosts white blood cell production for fighting off microbes. It has also received attention in labs for possible neurological applications.

Terms - Including some beneficial & detrimental compounds and their sources

The terms that are used when addressing the subject of plant chemicals can make the head spin. Here’s a reference on just some of them.

Terms A - E

Adaptogens -- Adaptogens are non-toxic plants that are marketed as helping the body resist stressors of all kinds, whether physical, chemical or biological. These herbs and roots have been used for centuries in Chinese and Ayurvedic healing traditions.

Anti-amyloid –- Chemicals (natural and synthetic) that decrease Amyloid beta (Aβ) in the human brain.

Anticholinesterase -- An enzyme (or drug) that blocks the action of acetylcholinesterase, thereby increasing the stimulating effect of acetylcholine (neurotransmitter).

Anti-inflammatory –- A substance (natural and synthetic) that has the property to reduce inflammation or swelling.

Antinutrient -- In plants, antinutrients are compounds designed to protect from bacterial infections and being eaten by insects. In humans, they interfere with the absorption of nutrients. Includes such things as protein trypsin inhibitor and lectins.

Antioxidant -- Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals and chain reactions that may damage the cells of organisms and cause inflammation in the body. Antioxidants keep the body in redox (reduction oxidation) balance.

Ashwagandha –- The ashwagandha plant is a small shrub with yellow flowers that’s native to India and Southeast Asia. People have used ashwagandha for thousands of years in traditional medicine. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease (Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, and clinical studies have shown these functions/outcomes: antioxidant, anti-inflammatory, blocks Aβ production, inhibits neural cell death, dendrite extension, neurite outgrowth and restores synaptic function, neural regeneration, reverses mitochondrial dysfunction, improves auditory–verbal working memory, executive function, processing speed, and social cognition in patients.

Beta-glucan -- Beta-glucans are soluble fibers that come from the cell walls of bacteria, fungi, yeasts, and some plants. Beta glucan has shown significant antimicrobial, anticancer, anti-diabetic, and anti-hypercholesterolemic (controls cholesterol levels) properties in numerous clinical trials.

Biotoxin -- Substances which are toxic and have a biological origin. They come in many forms and can be produced by nearly every type of living organism: there are mycotoxins (made by fungi), zootoxins (made by animals) and phytotoxins (made by plants).

Botanicals –- Medicines derived from plant sources or more broadly, something derived from plants.

Brahmi (Bacopa monnieri) -- An herb which occurs naturally in India that has a long history of use in the Ayurvedic medicine (ancient Indian medical system). According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, and clinical studies studies have shown these functions/outcomes: antioxidant, anti-inflammatory, improves memory, attention, executive function, blocks Aβ production, inhibits neural cell death, delays brain aging, improves cardiac function.

Brassica -- Genus of plants in the cabbage and mustard family. The members of the genus are informally known as cruciferous vegetables.

Caffeic Acid -- Caffeic acid contains biological antioxidant and neuroprotective properties. The neuroprotective reaction of caffeic acid can protect against the brain disruption from hydrogen peroxide produced by oxidative stress. It also enhances glutathione and superoxide dismutase activities, which protect against neuron cell loss caused by oxidative stress in the hippocampus. This paper Caffeic acid protects against l-methionine induced reduction in neurogenesis and cognitive impairment in a rat model(Apiwat Sirichoat et al, 25 Feb 2024) found a protective role of caffeic acid in hippocampal neurogenesis and cognitive impairment induced by L-methionine, which is consumed in high quantities in the average American diet.

Caffeic-Acid based Carbon Quantum Dots (CACQDs) -- Carbon Quantum Dots (CACQDs) are derived from used coffee grounds. CACQDs have shown neuroprotective effects in various models. They can remove free radicals and inhibit the aggregation of amyloid protein fragments. For further reading see Caffeic acid recarbonization: A green chemistry, sustainable carbon nano material platform to intervene in neurodegeneration induced by emerging contaminants (Jyotish Kumar et al, 15 Nov 2023)

Caffeine -- Caffeine is a trimethyl-xanthine found in various plants’ seeds, nuts, and leaves, such as coffee, cocoa beans, yerba matte and tea leaves, and guarana berries. Caffeine is the most widely consumed psychoactive alkaloid capable of crossing the BBB and influences cerebral functions such as objective and perceived cognitive performance and increases alertness and wakefulness and performance of memory tasks. Other effects include modification of the blood flow to the brain. Preclinical studies showed that caffeine could protect and reverse AD-like cognitive impairment in transgenic AD mice. Analysis demonstrated that caffeine increased the expression of the hippocampal brain-derived neurotrophic factor (BDNF) and TrkB. The levels of BDNF, and its primary receptor TrkB, have been reported to decrease in AD. Longitudinal clinical studies investigated caffeine consumption and its impact on cognitive impairment. Although there is no consensus on the results, some studies demonstrated a improved cognition after long-term caffeine consumption, reducing age-related cognitive impairment and creating a lower incidence of AD.

Carotenoids -- Any of a class of mainly yellow, orange, or red fat-soluble pigments, including carotene, which give color to plant parts such as ripe tomatoes, pumpkins, carrots, daffodils, and autumn leaves. They are terpenoids. Carotenoids are beneficial for eye health and immune health. Two of the six more common carotenoids — lutein and zeaxanthin — are found in the retina and can decrease your risk of developing macular degeneration by 43 percent, according to studies.

Cat’s claw (Uncaria tomentosa) -- Cat's claw is a woody vine that grows wild in the Amazon rainforest and other tropical areas of Central and South America. Its thorns resemble a cat's claws . Use of cat’s claw dates back 2,000 years. Indigenous people of South and Central America used it to ward off disease. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, pre-clinical studies have shown these functions/outcomes: anti-inflammatory, antioxidant, inhibits plaques and tangles, reduces gliosis, improves memory.

Catechins -- Catechin is a flavan-3-ol also known as flavanol, part of the chemical family of flavonoids (a polyphenol). Catechins are a type of phenolic compound found in berries, tea, and cocoa. Epidemiological studies have correlated diets high in green tea catechins and black tea theaflavins with a reduced incidence of Alzheimer's Disease. Studies have also demonstrated the varying inhibitory capabilities of catechins (epicatechin, epigallocatechin, epigallocatechin gallate) and theaflavins (theaflavin, theaflavin monogallate) towards amyloid beta (Aβ) oligomerization, the most toxic Aβ aggregate.

Chlorogenic acid -- Chlorogenic acid is among the most available phenolic acid compounds in foods such as coffee, berries, cocoa, tea, apples, and others. Chlorogenic acid and its metabolites are Blood Brain Barrier (BBB) permeable and can be widely distributed in the brain. A wide range of preclinical studies support that chlorogenic acid exhibits anti-inflammatory, antioxidant, and potent neurotrophic activity, which may contribute to reducing the risk of neurodegeneration.

Chinese medicinal herbs –- Plant products used in Chinese herbal medicine. The biggest difference between Western and traditional Chinese herbalism is that herbalists don’t treat symptoms or diseases, they treat the entire being, including their patterns of symptoms. Chinese herbal medicine is rooted in the concept of pattern differentiation. Pattern differentiation involves identifying a person’s head-to-toe collection of signs and symptoms. The majority of herbal formulas are customized to each person. Chinese herbal medicine has been practiced for thousands of years.

Cinnamic acid -- A key chemical found in plants such as Cinnamomum cassia (Chinese cinnamon) and Panax ginseng, fruits, whole grains, vegetables and honey. Studies have reported that cinnamic acid exhibit antioxidant, antimicrobial, anticancer, neuroprotective, anti-inflammatory and antidiabetic properties. According to this paper, Cinnamic Acid Derivatives and Their Biological Efficacy (Ngonidzashe Ruwizhi and Blessing Atim Aderibigbe, 9 Aug 2020) cinnamic acid derivatives have neuroprotective ability, including inhibiting cholinesterase.

Cinnamon -- Cinnamon was once valued more highly than gold, it certainly has many health benefits. Some compounds found in cinnamon have an effect on tau—a protein in the brain associated with Alzheimer's disease. Studies have found cinnamon to be neuroprotective, particularly in Parkinson's. Cinnamon is high in antioxidants. Cinnamon has been linked to reduced blood pressure, triglycerides, cholesterol levels and blood sugar in those with metabolic diseases. Studies suggest cinnamon might be able to reduce insulin resistance. Cinnamon is a natural anti-inflammatory that blocks the release of arachidonic acid, a fatty acid that causes inflammation. Arachidonic acid can also cause blood clotting. There are two different kinds of cinnamon — Cassia and Ceylon. Both posses the helpful qualities just described, however, Cassia cinnamon contains the toxin coumarin, a compound found in some plant species that can be harmful if consumed in high quantities. Ceylon is also known as "true cinnamon". Cassia is the most common cinnamon found in supermarkets and it's generally cheaper than Ceylon cinnamon.

Cinnamomum cassia -- Chinese cinnamon.

Cocoa -- The cocoa bean is the seed of the cacao tree and is widely recognized as one of the main sources of phenolic compounds with the highest flavanols content of all foods on a per weight basis. The bioactive compounds hold potential benefits in the prevention of chronic diseases associated with inflammation, oxidative stress, and metabolic disorders. Research has shown that cocoa and cocoa-derived products have many cardiovascular benefits. In recent years, neuromodulation and neuroprotective properties have also been suggested. Papers on the protective qualities of cocoa include,Benefits in Cognitive Function, Blood Pressure, and Insulin Resistance Through Cocoa Flavanol Consumption in Elderly Subjects With Mild Cognitive Impairment (Giovambattista Desider et al, 14 Aug 2012) and Cocoa Flavanols: Natural Agents with Attenuating Effects on Metabolic Syndrome Risk Factors (Maria Eugenia Jaramillo Flores, Apr 2019).

Coffee fruit extract -- A product of the coffee plant fruit (coffee “beans” are actually seeds of the fruit). After the seeds (coffee beans) are removed, the remaining pulp of the fruit has been found to be high in polyphenols that boosts brain-derived neurotrophic factor (BDNF) significantly. BDNF has been called “miracle grow” for the brain. BDNF is the most active neurotrophin. Neurotrophins induce survival, development, and function of neurons. Coffee fruit extract is available as a supplement.

Coffee Grounds -- See Caffeic-Acid based Carbon Quantum Dots (CACQDs).

Coumarin –- Coumarins are phenolic substances. At least 1300 different coumarins have been identified. Coumarins have antithrombotic (reduces blood clots), anti-inflammatory, and vasodilatory (open (dilate) blood vessels) activities.

Cruciferous vegetables -- Vegetables of the family Brassicaceae, a diverse group that includes broccoli, cauliflower, cabbage, kale, bok choy, arugula, Brussels sprouts, collards, watercress and radishes. Most cruciferous vegetables are rich in vitamins and minerals such as folate and vitamin K. Dark green cruciferous veggies also are a source of vitamins A and C and phytonutrients.

Curcumin -- Polyphenol found in turmeric, a spice that has long been recognized for its medicinal properties. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. According to this paper, Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer’s Disease (Ines Elbini et al, 18 May 2021) there are numerous studies highlighting the beneficial effects of curcumin and "Our results showed that treatment with CUR [curcumin] enhances pro-oxidant levels, antioxidant enzymes activities and anti-inflammatory cytokine production and decreases apoptotic cells in AlCl3-exposed hippocampus rats. Additionally, histopathological analysis of hippocampus revealed the potential of CUR in decreasing the hallmarks in the AlCl3-induced AD. We also showed that CUR post-treatment significantly improved the behavioral, oxidative stress and inflammation in AlCl3-exposed rats. Taken together, our data presented CUR as a nutraceutical potential through its protective effects that are more interesting than recovery ones in sporadic model of AD." However, ingesting curcumin by itself does not lead to associated health benefits due to poor bioavailability. Several components can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. [Source: Curcumin: A Review of Its’ Effects on Human Health (Susan J. Hewlings and Douglas S. Kalman, 22 Oct 2017)

Dieckol -- A polyphenol derived from Arame (a seaweed). It has attracted attention as a bioactive ingredient for preventing Alzheimer’s disease (AD). Dieckol has anti-bacterial, anti-cancer, anti-oxidant, anti-aging, anti-diabetic, neuroprotective actions. Dieckol plays an important role in apoptosis (death of cells) induction and remarkably inhibited the lipid accumulation in high fat diet induced animal models (Source: Dieckol: a brown algal phlorotannin with biological potential (Durairaj Karthick Rajan et al, Oct 2021)). For more information on Dieckol see: Investigating the Potential Anti-Alzheimer’s Disease Mechanism of Marine Polyphenols: Insights from Network Pharmacology and Molecular Docking (Kumju Youn et al, 6 Nov 2023).

ECGC (Epigallocatechin Gallate) -- A unique plant compound that acts as an antioxidant and is thought to reduce inflammation, aid weight loss, and help prevent heart and brain disease. Predominantly found in green tea, exists in small amounts in other foods, such as other teas: oolong and black; fruits: cranberries, strawberries, blackberries, kiwis, cherries, pears, peaches, apples, and avocados; and nuts: pecans, pistachios, and hazelnuts.

Eckol -- A polyphenol derived from brown algae (a seaweed). It has attracted attention as a bioactive ingredient for preventing Alzheimer’s disease (AD). Qualities of eckol that are of particular interest to ApoE4s include: Anti-Oxidant, Anti-Diabetic, Neuroprotective, Anti-Inflammatory, and Anti-Hyperlipidemic. Other therapeutic qualities include: Hepatoprotective, , Radioprotective, Anti-Photo Aging Effects, Anti-Hypertensive, Anticoagulative, Antibacterial and Antiviral Activity, Anti-Obesity, Anticancer, Anti-Histaminic, and Anti-Tyrosinase. For more information see: Characterizing Eckol as a Therapeutic Aid: A Systematic Review (Bandana Manandhar et al, 18 Jun 2019) and Investigating the Potential Anti-Alzheimer’s Disease Mechanism of Marine Polyphenols: Insights from Network Pharmacology and Molecular Docking (Kumju Youn et al, 6 Nov 2023).

Ellagitannins -- Ellagitannins are a diverse class of hydrolyzable tannins, a type of polyphenol. Ellagitannins, ellagic acid, and their metabolites have been reported to exhibit numerous beneficial effects on human health including anti-inflammatory, anticancer, antioxidant, prebiotic, and cardioprotective properties. (Source: Food Ellagitannins: Structure, Metabolomic Fate, and Biological Properties (Karen Johana Ortega Villalba et al, 26 July 2019). Ellagitannins are bioconverted by microbiota in the gut into metabolites called urolithins. Ellagitannin-rich sources include pomegranates, walnuts, strawberries, and more.

Ergosterol -- A sterol that resides on the cell membranes of fungi which act to maintain cell membrane integrity, similar to mammalian cholesterol. Positive benefits attributed to ergosterol include: antioxidant, anti-inflammatory, anticancer, antidiabetic, neuroprotective, antimicrobial, anti-hepatic steatosis. For more on ergosterol, Potential Beneficial Effects and Pharmacological Properties of Ergosterol, a Common Bioactive Compound in Edible Mushrooms(Panthakarn Rangsinth et al, 29 June 2023)

Ergothioneine -- A naturally occurring amino acid. It is found in relatively few organisms, mainly in mushrooms. Ergothioneine improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer's disease (source: Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer’s disease (Printha Wijesinghe et al, 14 Mar 2023)

Erinacines -- These are a constituent of Hericium erinaceus, better known as the Lion’s Mane mushroom. Erinacines are known to cross the blood brain barrier and appears to be the key component responsible for the neurotrophic and neuroprotective activities of Lion’s Mane. Specifically erinacines are strong inducers of Nerve Growth Factor (NGF) synthesis both in vitro and in vivo. Additionally, erinacines have been found to decrease amyloid-ß plaque deposition, increase expression of insulin-degrading enzyme, and mitigate neuropathic pain.

Terms F - J

Fisetin -- A plant flavonol from the flavonoid group of polyphenols. Found in many plants, where it serves as a yellow/ochre coloring agent. Found in many fruits and vegetables, such as strawberries, apples, persimmons, onions and cucumbers. Fisetin is a sirtuin-activating compound. It has been shown to be an effective senolytic agent (i.e. clears senescent cells, cells that don't die off when they should), with effects of increased lifespan, reduced senescence markers in tissues, and reduced age-related pathologies. Fisetin has been shown to inhibit the activity of several pro-inflammatory cytokines and to upregulate glutathione, an endogenous antioxidant. It has direct activity as a reducing agent, chemically reacting with reactive oxygen species to neutralize them. Studies suggest that it lodges in cell membranes and prevents oxidative damage to lipids in the cell membrane. For more reading on Fisetin, seeThe neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress(Syed Shams ul Hassan et al, 10 Oct 2022)

Flavan-3-ols -– See flavanol.

Flavanols –- Flavanols or flavan-3-ols is a class of flavonoid (a polyphenol). They represent the most common flavonoids consumed in the American diet. Tea, chocolate, grapes, apples, and red wine are some of the prominent sources of these polyphenols

Flavones -- A class of flavonoid (a polyphenol). Common in foods, mainly from spices, and some yellow or orange fruits and vegetables. Shown in both vitro and in vivo to have neuroprotective effects.

Flavonoids – One of the four main groupings of polyphenols. More than 8,000 compounds with flavonoids structure have been identified, many of which are responsible for the attractive colors of flowers, fruits and leaves. In plants, these compounds afford protection against ultraviolet radiation, pathogens, and herbivores. Flavonoids play an important role in the prevention of diseases related to oxidative stress and possess antibacterial, antiviral, and anti-inflammatory, and anti-carcinogenic effects.

Fungi -- Fungi are not plants but are a class of eukaryotes (organisms whose cells contain a nucleus and membrane-bound organelles). They include yeasts, molds and mushrooms.

Ginger (Zingiber officinale) -- Ginger contains many bioactive components and has been used for thousands of years for the treatment of numerous ailments. The medicinal, chemical, and pharmacological properties of ginger have been extensively reviewed (Source: Chapter 7 The Amazing and Mighty Ginger(Ann M. Bode and Zigang Dong, 2011). Of interest to ApoE4s is ginger’s antioxidant, anti-inflammatory, and cardiovascular disease preventative qualities. Ginger has been found to help control blood sugar levels. Ginger may also enhance cognitive function. A randomized, double-blind, placebo-controlled study concluded that ginger improves working memory in middle-aged, healthy women. (Source: Zingiber officinale Improves Cognitive Function of the Middle-Aged Healthy Women (Naritsara Saenghong et al, 22 Dec 2011) Combining ginger with cinnamomum cassia (Chinese cinnamon) produced synergistic anti-diabetic, antioxidant, anti-inflammatory, antidepressant-like, and neuroprotective effects (Source: Synergistic Anti-inflammatory and Neuroprotective Effects of Cinnamomum cassia and Zingiber officinale Alleviate Diabetes-Induced Hippocampal Changes in Male Albino Rats: Structural and Molecular Evidence(Hailah M. ALmohaimeed et al, 8 Sep 2021). An exploration of ginger’s active substances that regulate AD and their mechanisms are discussed in this paper Screening of Active Substances Regulating Alzheimer’s Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets(Pan Y et al, 2/18/2024).

Ginkgo (Ginkgo biloba) -- A large tree thought to be one of the oldest living trees, dating back more than 200 million years, native to China, Japan, and Korea. The most helpful components of ginkgo are the flavonoids which have powerful antioxidant qualities, and terpenoids which help improve circulation by dilating blood vessels and reducing the "stickiness" of platelets. Most of the research on ginkgo focuses on its effect on dementia, memory and pain caused by too little blood flow. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease (Julie Gregory et al, 8 Apr 2021) in vitro, pre-clinical and clinical studies have shown these functions/outcomes: antioxidant, improves mitochondrial function, stimulates cerebral blood, flow, blocks neural cell death, stimulates neurogenesis.

Glutathione -- An antioxidant in plants, animals, fungi, and some bacteria and archaea. Known as the mother of antioxidents, the master detoxifier, and maestro of the immune system. Your body also produces glutathione, but poor diet, air pollution, toxins, medications, stress, trauma, aging, infections and radiation deplete it. Glutathione is involved in tissue building and repair, making chemicals and proteins needed in the body, and in immune system function. Dr Mark Hyman, well-known functional medicine expert has found glutathione deficiency in nearly all very ill patients. The strength of glutathione comes from the sulfur chemical groups it contains. Sulfur rich foods aid in boosting glutathione levels. Some plants rich in sulfur include: cauliflower, broccoli, cabbage, asparagus, brussel sprouts, turnips, radishes, onions, and garlic.

Gluten –- Proteins (a lectin) found in wheat (wheatberries, durum, emmer, semolina, spelt, farina, farro, graham, KAMUT® khorasan wheat and einkorn), rye, barley and triticale. Many processed foods may also contain gluten. Celiac disease, an autoimmune disorder, is the most severe form of gluten intolerance, but people can have gluten sensitivity without celiac disease. Gluten activates the protein zonulin which is a protein that modulates the permeability of tight junctions between cells of the wall of the digestive tract. Thus zonulin loosens the tight junctions and makes the intestinal barrier more permeable, i.e. leaky gut. See Gut-Brain Connection: Leaky Gut/Leaky Brain, Microbiome (gut bugs)

Glycyrrhizin -- A plant glycoside extracted from roots of the liquorice plant. Glycyrrhizin has been used in traditional medicine as an expectorant in cough syrups and as herbal remedy for treating stomach ulcers and constipation. It has also been found to prevent the postoperative cognitive impairment by reducing neuroinflammation and Alzheimer’s-related pathology in the hippocampus of aged mice via HMGB1 inhibition. [Source: The Oral Pretreatment of Glycyrrhizin Prevents Surgery-Induced Cognitive Impairment in Aged Mice by Reducing Neuroinflammation and Alzheimer’s-Related Pathology via HMGB1 Inhibition (Zhong-Hong Kong et al, 16 Oct 2017)].

Gotu kola (Centella asiatica) -- Gotu kola is a perennial plant native to India, Japan, China, Indonesia, South Africa, Sri Lanka, and the South Pacific. A member of the parsley family. Gotu kola (Centella asiatica) has been used to treat many conditions for thousands of years in India, China, and Indonesia. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease (Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, clinical studies have shown these functions/outcomes: neuroceutical, cogniceutical, reduces oxidative stress, Aβ levels, and apoptosis, promotes dendritic growth and mitochondrial health, improves mood and memory.

Gou-Teng or Chotoko (Uncaria rhynchophylla) -- An eastern medicine and major component of 'Yokukansan' for the treatment of agitation in elderly persons. It appears to be neuroprotective, anticonvulsive, and has antipsychotic properties like Aripiprazole. Used in traditional Chinese and Japanese medicine for the treatment of hypertension, convulsive disorders (epilepsy), and for various head ailments such as headache or dizziness. It contains a variety of alkaloid structures.

Herb -- Herbs are a widespread group of plants, excluding vegetables and other plants consumed for macronutrients. They have savory or aromatic properties for flavoring and garnishing food, for medicinal purposes, or for fragrances. Culinary use typically distinguishes herbs from spices. Herbs generally refers to the leafy green or flowering parts of a plant (either fresh or dried), while spices are usually dried and produced from other parts of the plant, such as seeds, bark, roots and fruits.

Huperzine-A -- A chemical that comes from Chinese club moss (Huperzia serrata) or fir club moss (Huperzia selago) plants. Huperzine A is a naturally occurring sesquiterpene alkaloid compound. It is a cognitive enhancer that inhibits an enzyme that degrades the learning neurotransmitter, acetylcholine; due to this, a relative increase occurs. It belongs to the cholinergics class of molecules.

Isoflavonoids -- Families a class of flavonoid phenolic compounds (a polyphenol). Isoflavonoids include isoflavones, isoflavanones, isoflavans, rotenoids and pterocarpans. Isoflavonoids and their derivatives are sometimes referred to as phytoestrogens, as many isoflavonoid compounds exert pseudohormonal activity by binding to estrogen receptors. Soy and its products, and legume seeds (lentils, beans, peas) are the richest sources of isoflavones. The potential health benefits of isoflavones may include protection against age-related diseases including cardiovascular disease, osteoporosis, hormone-dependent cancer and loss of cognitive function.

Isorhamnetin --A flavonoid compound present in the leaves, flowers and fruits of Hippophae rhamnoides, Ginkgo biloba and other plants. Studies have shown that isorhamnetin has a wide range of pharmacological effects on cardiovascular diseases, a variety of tumors, and possesses the potential of preventing neurodegenerative diseases such as Alzheimer’s disease. In this study, Dietary flavonols and risk of Alzheimer dementia (Thomas M. Holland et al, 21 Apr 2020) isorhamnetin, kaempferol, and myricetin were the most significant flavonol constituents and were found to be associated with a reduction of 38%, 50%, and 38%, respectively, in the rate of incident of Alzheimer disease, for those in the fifth vs first quintile of intake.

Terms K - O

Kaempferol -- Is a natural flavonol found in a variety of plants and plant-derived foods including kale, beans, tea, spinach, and broccoli. Kaempferol augments human body's antioxidant defense against free radicals. Kaempferol modulates apoptosis, angiogenesis, inflammation, and metastasis. In this study, Dietary flavonols and risk of Alzheimer dementia (Thomas M. Holland et al, 21 Apr 2020) isorhamnetin, kaempferol, and myricetin were the most significant flavonol constituents and were found to be associated with a reduction of 38%, 50%, and 38%, respectively, in the rate of incident of Alzheimer disease, for those in the fifth vs first quintile of intake. The richest plant sources of kaempferol are green leafy vegetables, including spinach and kale, and herbs such as dill, chives, and tarragon.

Lectins -- Lectins are a family of proteins found in many foods. Plant sources include grains, legumes, the squash family (a fruit), and vegetables of the nightshade family. Lectins can also be found in meat, poultry, fish, diary products and eggs. The same features that plant containing lectins use to defend themselves can cause problems during human digestion. They resist being broken down in the gut and are stable in acidic environments. Lectins cause increased gut permeability and drive autoimmune diseases, (see Gut-Brain Connection: Leaky Gut/Leaky Brain, Microbiome (gut bugs)). While certain lectins are toxic and cause harm when consumed in excess, many can be neutralized with proper cooking techniques such as pressure cooking.

Limonoids -- Limonoids are phytochemicals of the triterpenoid class which are abundant in sweet or sour-scented citrus fruit and other plants. The biological activity of citrus limonoids has indicated the potential of these compounds to improve human health as anticancer, cholesterol-lowering, and antiviral agents.

Lion’s mane (Hericium erinaceus) -- Also known as monkey head mushroom or bearded tooth mushroom. Lion's mane is a mushroom that grows on trunks of dead hardwood trees such as oak. It has a long history of use in traditional Chinese medicine. Regular consumption promotes nerve and brain health. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease (Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, pre-clinical and clinical studies have shown these functions/outcomes: neuroprotective, improves cognition, anti-inflammatory, blocks Aβ production, stimulates neurotransmission and neurite outgrowth.

L-theanine -- An amino acid found primarily in green and black tea and some mushrooms. It’s also available in pill or tablet form. Theanine is structurally similar to the excitatory neurotransmitter glutamate, and in accordance, binds to glutamate receptors in vitro, though with much lower affinity in comparison. It’s said to help ease anxiety, stress, and reduce insomnia. Paired with caffeine, L-theanine may help increase focus and attention. Some research suggests that L-theanine may improve the function of the body’s immune system.

Luteolin -- Luteolin is a flavonoid widely distributed in vegetables and fruits, such as celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages, apple skins, and chrysanthemum flowers. It has been shown that this flavone possesses a variety of therapeutic activities, including antioxidant, anti-inflammatory, and anticancer. Luteolin is Blood-Brain Barrier (BBB) permeable and can be detected in brain tissues after oral intake.

Matcha -- A finely ground powder of specially grown and processed green tea leaves. The powdered form of matcha is consumed differently from tea leaves or tea bags, as it is suspended in a liquid, typically water or milk. The traditional Japanese tea ceremony centers on the preparation, serving and drinking of matcha as hot tea. Matcha tea has the highest concentration of the flavonoid EGCG (epigallocatechin-3-gallate), 137% more than green tea. This flavonoid can bind to beta-amyloid proteins to prevent formations. Matcha also contains a stress-reducing amino acid, theanine. Source organic matcha tea from Japan (not China) to avoid heavy metal contamination. Also, keep your water below 170 degrees F to preserve the health benefits.

Myricetin -- Member of the flavonoid class of polyphenolic compounds. Holds antioxidant properties. Common dietary sources include vegetables, fruits, nuts, berries, tea, and red wine. According to the research paper (behind a paywall) cited by this article More Evidence Flavanols in Tea, Fruit, and Veg Preserve Memory, Cognition Three specific components of flavonols in particular — kaempferol, myricetin, and quercetin — were associated with slower global cognitive decline. In this study, Dietary flavonols and risk of Alzheimer dementia(Thomas M. Holland et al, 21 Apr 2020) isorhamnetin, kaempferol, and myricetin were the most significant flavonol constituents and were found to be associated with a reduction of 38%, 50%, and 38%, respectively, in the rate of incident of Alzheimer disease, for those in the fifth vs first quintile of intake.

Natural compounds -- A chemical compound or substance produced by a living organism—that is, found in nature.

New world fruits and vegetables –- Native to the Americas, include foods from the bean family (legumes, peanuts, cashews), grains, pseudo-grains such as amaranth and quinoa, the squash family (pumpkins, acorn squash, zucchini) as well as chia and certain seeds. Introduced to Europe, Africa and Asia by European explorers after 1492.

Nightshades -- Family of plants that includes tomatoes, eggplant, potatoes, and peppers. The lectins in the nightshade family include solanine, a neurotoxic glycoalkaloid poison.

Nobiletin -- Nobiletin is a flavonoid isolated from citrus peels. It has shown antioxidant, anti-inflammatory, and antiangiogenic activity in vitro and in vivo. Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer’s Disease and Parkinson’s Disease(Akira Nakajima1 and Yasushi Ohizumi Jul 2019) indicates that nobiletin improved cognitive deficits and the pathological features of AD, such as Aβ pathology, hyperphosphorylation of tau, and oxidative stress, in animal models of AD.

Nootropic -- Nootropics can either be synthetic (produced in a laboratory) or can occur naturally as herbal plants like Ginkgo biloba and American Ginseng. Natural nootropics aid in promoting the brain function with a simultaneous improvement in brain health. They also act as vasodilators (open (dilate) blood vessels) against the small arteries and veins in the brain. They tend to increase the blood circulation towards the brain with an upsurge in the vital nutrients, energy, and oxygen flow in brain. They also mitigate the inflammatory responses in the brain. Natural nootropics also modulate neurotransmitter concentration in the brain.

Nutraceutical -- A nutraceutical is defined as any substance that is a food or part of a food and provides medical or health benefits, including the prevention and treatment of disease.

Oleocanthal -- A polyphenol found in Virgin Olive Oil. Has been reported to exhibit various modes of action in reducing inflammatory related disease, including joint-degenerative disease, neuro-degenerative disease, and specific cancers. Oleocanthal along with oleuropein (another polyphenol in virgin olive oil) have been reported to interfere with the amyloid aggregation of amyloid beta (Aβ), amylin (co-secreted with insulin and also plays an important role in controlling blood glucose), and Tau.

Oxalates -- Also known as oxalic acid although they are actually distinct chemically. Oxalates can be consumed through certain plants as well as produced as waste by our bodies. Foods high in oxalates are rich in many beneficial nutrients, however, because oxalates bind to calcium as they exit the body, they can increase the risk of kidney stones in some people. If prone to kidney stones or have kidney disease, a low-oxalate diet is advised. However, for most people, the benefits of high-oxalate foods can outweigh their risks. Certain practices can reduce the impact of oxalates, such as: drinking plenty of water, consuming enough calcium to bind to the oxalates, limiting sodium and sugar intake, getting recommended amounts of vitamin C without too much as that increases oxalic acid production in the body, eating cooked vegetables. Foods high in oxalates: spinach, soy products, almonds, potatoes, beets, navy beans, raspberries dates. For greater discussion on oxalate see Oxalates

Oxyimperatorin -- Oxyimperatorin abbreviated as OIMP, is a member of furanocoumarin, isolated from the medicinal herb Glehnia littoralis. According to this paper, Oxyimperatorin attenuates LPS-induced microglial activation in vitro and in vivo via suppressing NF-κB p65 signaling (Changcheng Lu et al, 22 Mar 2024) the purpose of which was to investigate the neuroprotective activity of oxyimperatorin (OIMP) in LPS-induced neuroinflammation in vitro and in vivo models, the conclusion stated, "Our findings suggest that OIMP suppresses microglia activation and attenuates the production of pro-inflammatory mediators and cytokines via inhibition of NF-κB p65 signaling."

Terms P - T

Phenolic acid -- Phenolic acids are among the most widely distributed plant non-flavonoid phenolic compounds. Phenolic acid accounts for about 30% of all known polyphenols. Phenolic acids are commonly found and well documented for health protective effects like antimicrobial, anticancer, anti-inflammatory, anti-mutagenic, and more. Phenolic acid is found in foods like grapes, berries, pomegranates, walnuts, chocolate, coffee, and green tea. The key advantage of using phenolic acids is their metabolizing ability by natural microbes; therefore provide an essential alternate to man-made chemicals which are harmful to environment also.

Phenolic compounds -- Phytochemicals that are found in most plant tissues. Phenolic compounds are a group of small molecules characterized by their structures having at least one phenol unit. If more than one phenol unit, it is a polyphenol.

Phenolics –- Another name for polyphenols.

Phlorotannins -- A marine polyphenol, a type of tannin found in certain seaweeds.

Phyllodulcin -- a major component of hydrangea. In this mouse study, Phyllodulcin improves hippocampal long-term potentiation in 5XFAD mice (Eunbi Cho et al, May 2023) phyllodulcin was found to inhibit Aβ aggregation and dissociate Aβ aggregates, inhibited Aβ aggregates-induced cytotoxicity, improved Aβ aggregate-induced memory and long-term potentiation impairments, reduced Aβ plaques and neuroinflammation in 5XFAD mice, and improved hippocampal long-term potentiation in 5XFAD mice suggesting that phyllodulcin may be a candidate for the treatment of AD.

Phytochemicals -- Interchangeable with phytonutrients.

Phytoestrogens -- Estrogen-like compounds derived from plants. The four phenolic compounds classified as phytoestrogens are isoflavones, stilbene, coumestan, and lignan. They have been found to be beneficial in combatting symptoms and conditions caused by estrogen deficiency. However, since they act in a similar way as synthetic estrogen they may carry the same risks and may increase obesity, cancer, and problems with reproduction.

Phytonutrient -- Literally means plant nutrient, also called phytochemicals, These are natural chemicals that are found in plant foods.

Phytotoxin –- Toxic substance made by plants.

Polyphenol -- Polyphenols are a group of compounds found in plant foods that are beneficial for health. Discussed in greater depth above.

Polysaccharides -- A carbohydrate whose molecules consist of a number of sugar molecules bonded together (poly = many, saccharide = sugar). Derived from plant foods, polysaccharides are major components of the human diet. In particular, starch and other storage carbohydrates are the major sources of energy in all diets. Cell wall polysaccharides are the major components of dietary fiber.

Psilocybin -- A psychoactive ingredient in some psychedelic species of fungi (magic mushrooms). Added to this list due to the attention it has gained in recent years for treatment of mental conditions like anxiety, depression and PTSD, but little is known as to any efficacy this substance has to offer in treating or preventing Alzheimer’s. One study did show a low dose increased neurogenesis in mice but a high dosage significantly decreased neurogenesis. In addition to impacting hippocampal neurogenesis, these psychedelic compounds are believed to promote neuroplasticity, but this is yet to be proven in humans. Possession and usage is also largely prohibited by law.

Quercetin -- A plant pigment (flavonoid). Found in many plants and foods, such as red wine, onions, green tea, apples, and berries. It is also a compound with a neuroprotective potential against age-related neurodegenerative diseases such as Alzheimer's disease (AD) although clinical application of quercetin is hampered by its low oral bioavailability. It is also known for its anti-inflammatory, antihypertensive, vasodilator effects, antiobesity, antihypercholesterolemic and antiatherosclerotic activities. Quercetin is contained in abundance in apples, honey, raspberries, onions, red grapes, cherries, citrus fruits, and green leafy vegetables. Quercetin content is highest in onions. According to the research paper (behind a paywall) cited by this article More Evidence Flavanols in Tea, Fruit, and Veg Preserve Memory, Cognition Three specific components of flavonols in particular — kaempferol, myricetin, and quercetin — were associated with slower global cognitive decline.

Resveratrol -– A polyphenol belonging to the stilbenoids group. It has been found in more than 70 plant species, especially in grapes’ skin and seeds. It is a phytoalexin that acts against pathogens, including bacteria and fungi. Numerous studies have demonstrated that resveratrol, as a natural food ingredient, possesses a very high antioxidant potential. Other bioactive effects include being anti-inflammatory, anticarcinogenic, cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective. However, resveratrol application is a challenge due to its poor solubility and bioavailability, as well as certain adverse effects.

ROS (Reactive Oxygen Species) -- Reactive oxygen species are free radicals, a type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell. A build up of reactive oxygen species in cells may cause damage to DNA, RNA, and proteins, and may cause cell death. When there is an imbalance between the amount of ROS and antioxidants in the body, the result is oxidative stress. Most of the health benefits of polyphenols relate to their role as an antioxidant to neutralize free radicals.

Rose -- Various parts of rose such as fruits, flowers, leaves, and bark can be used in various products. The medical benefits of roses include the treatment of inflammation, diabetes, dysmenorrhea, depression, stress, seizures, and aging. (Source: Beneficial medicinal effects and material applications of rose (Hsiuying Wang, 8 Dec 2023)

Rosmarinic acid -- Rosmarinic acid is an ester of caffeic acid and is detectable mostly in plants of the Lamiaceae family, particularly the rosemary Rosmarinus officinalis. Rosmarinic acid has a variety of biological activities such as antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective. However, it has a low BBB penetration, limiting brain accumulation. Although rosmarinic acid exhibits a low availability, its neuroprotective properties suggest that it may be a promising candidate for treating AD.

Saffron (Crocus sativus) -- Saffron is a spice derived from the flower of Crocus sativus, commonly known as the "saffron crocus". The vivid crimson stigma and styles, called threads, are collected and dried for use mainly as a seasoning and colouring agent in food. It is the most expensive spice in the world due to its labor-intensive harvesting method. Saffron is rich in plant compounds that act as antioxidants. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease (Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, and clinical studies have shown these functions/outcomes: antioxidant, anti-amyloidogenic, anti-inflammatory, antidepressant, immunomodulation, neuroprotection.

Secondary metabolites -- Substances produced by living things that are not directly involved in the normal growth, development, or reproduction of the organism.

Shankhpushpi (Convolvulus pluricaulis) -- Shankhpushpi is an herb found in India and Burma that is used in Ayurveda (ancient Indian medical system) for both cognitive and digestive wellness. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease (Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, and pre-clinical studies have shown these functions/outcomes: promotes cognitive function, slows brain aging, antioxidant, and anti-inflammatory.

Soy Isoflavones -- Soy is unique in that it contains a high concentration of isoflavones, a type of plant estrogen (phytoestrogen) that is similar in function to human estrogen but with much weaker effects. Soy isoflavones can bind to estrogen receptors in the body and cause either weak estrogenic or anti-estrogenic activity.

Spice -- A spice is a seed, fruit, root, bark, or other plant substance primarily used for flavoring or coloring food. Spices are distinguished from herbs, which are the leaves, flowers, or stems of plants used for flavoring or as a garnish.

Sterols -- Sterols are a subgroup of steroids. They occur naturally in most eukaryotes (organisms whose cells contain a nucleus and membrane-bound organelles) including plants, animals, and fungi. Plant sterols are substances that are similar to cholesterol but are made in plants. Plant sterols might help reduce cholesterol levels by limiting the amount of cholesterol that is able to enter the body.

Sulforaphane -- Sulforaphane is a bioactive compound derived from certain cruciferous vegetables, particularly broccoli (and its sprouts) and red kale. Robust evidence from epidemiological, clinical, rodent, and in vitro studies has demonstrated that sulforaphane exhibits antioxidant and anti-inflammatory properties and may be beneficial against a wide range of chronic and acute diseases. It may also ameliorate some of the harmful effects associated with exposure to air pollution.

Sulfur -- Sulfur is one of the three most abundant minerals in the human body. Sulfur plays an important role in crucial functions in your body, such as making protein, regulating gene expression, building and repairing DNA, and helping your body metabolize food. It is also essential for making and recycling glutathione — one of the body’s main antioxidants that help reduce inflammation and prevent cell damage caused by oxidative stress. Although too much may cause unpleasant side effects in anyone. Some people report feeling better when following a low sulfur diet, although it is thought to be the sulfites: a preservative derived from sulfur that’s added to some alcoholic beverages and packaged foods. Sulfur is found in a large variety of foods, not just plants. Some plants rich in sulfur include: cauliflower, broccoli, cabbage, asparagus, brussel sprouts, turnips, radishes, onions, and garlic.

Tannins – (also tannic acid) -- Bitter and astringent, tannins are water-soluble polyphenols that are present in many plant foods. Tannins are found commonly in the bark of trees, wood, leaves, buds, stems, fruits, seeds, roots, and plant galls. Tannins help to protect the plant/tree from predation. Foods with tannins: Pomegranates, strawberries, cranberries, blueberries, nuts, spices such as Cloves, tarragon, cumin, thyme, vanilla, and cinnamon, Most legumes, chocolate liquor, tea, coffee, wines aged in charred oak barrels, certain wine grapes grown in clay soils also contribute to tannins, orange-colored fruit juices often contain tannins from food coloring. Some fruit juices, sometimes even added to create a more astringent feel to the taste, beer. In large amounts, tannic acid can cause side effects such as stomach irritation, nausea, vomiting, and liver damage.

Terpenoids -- Largest class of plant secondary metabolites, with basic functions in growth and development, and more specialized roles in plant–environment interactions, resistance/tolerance to environmental stresses, and defense against predators and pathogens. Terpenoids otherwise known as isoprenoids are a large and diverse class of naturally occurring compounds derived from five carbon isoprene units. Terpenes are simple hydrocarbons, while terpenoids are modified class of terpenes with different functional groups and oxidized methyl group moved or removed at various positions.

Trigonelline -- Trigonelline is also plant alkaloid found in many plants. It has been isolated from the Japanese radish, fenugreek seeds, coffee and coffee byproducts. Higher levels of trigonelline are found in arabica coffee. Trigonelline is also a methylation product of niacin (vitamin B3). Trigonelline has been extensively studied for its numerous biological activities, including antimicrobial, antitumor, antidiabetic, antihypertensive, and antihyperlipidemic effects. The effects of trigonelline on age-related cognitive decline and the underlying molecular mechanisms have yet to be thoroughly studied, nevertheless, according to this mouse study, Transcriptomics and biochemical evidence of trigonelline ameliorating learning and memory decline in the senescence-accelerated mouse prone 8 (SAMP8) model by suppressing proinflammatory cytokines and elevating neurotransmitter release (Sharmin Aktar et al, 18 Sept 2023) researchers discovered that signaling pathways related to the development of the nervous system, mitochondrial function, ATP synthesis, inflammation, autophagy, and neurotransmitter release were significantly modulated in the trigonelline group. Furthermore, scientists found that trigonelline suppressed neuroinflammation. negatively regulating Traf6 signaling factor-mediated activation of the transcription factor NF-κB. Additionally, quantitative protein analysis confirmed the levels of inflammatory cytokines. TNF-α and IL-6 significantly decreased, and levels of the neurotransmitters dopamine, norepinephrine, and serotonin significantly increased in the hippocampus. All this suggests the potential of trigonelline in alleviating age-related memory and spatial disorders.

Triphala (Emblica officinalis, Terminalia bellerica, and Terminalia chebula) -- Triphala is a powerful herbal remedy, a staple in traditional Ayurvedic medicine (ancient Indian medical system). It is a mixture of the dried fruits of three medicinal plants native to India. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease (Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, pre-clinical and clinical studies have shown these functions/outcomes: antioxidant, anti-inflammatory, immunomodulation, prevents dental caries, antibacterial, antiparasitic, reverses metabolic disturbances.

Trypsin inhibitor –- Found in soybeans, grains, cereals and various additional legumes. Trypsin inhibitors strongly inhibit the activity of key pancreatic enzymes trypsin and chymotrypsin thereby reducing digestion and absorption of dietary proteins by the formation of complexes that are indigestible even in the presence of high amounts of digestive enzymes

Tubers -- A thickened underground part of some plants used by the plant for storage of nutrients.

Turmeric (Curcuma longa) –- Turmeric is a traditional Indian spice, a major ingredient in curry powder. It comes from the root of the curcuma longa plant, which is a perennial in the ginger family. Turmeric contains the powerful polyphenol curcumin. According to Table 1 Neuroprotective Herbs for the Management of Alzheimer’s Disease (Julie Gregory et al, 8 Apr 2021) in vitro, in vivo, pre-clinical and clinical studies have shown these functions/outcomes: antioxidant, anti-inflammatory, antimicrobial, blocks Aβ production, and inhibits neural cell death. Also see: Turmeric and Curcumin

Terms U - Z

Urolithins -- Urolithins are metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid. Ellagitannin-rich sources include pomegranates, walnuts, strawberries, and more. There are 13 known urolithins. Urolithin A has been shown to promote mitochondrial health and muscle endurance. Accumulating evidence has suggested that urolithins may have specific advantages in preventing brain aging including favorable blood–brain barrier permeability, selective brain distribution, and increasingly supporting data from preclinical and clinical studies. However, their usability in diagnosis, prevention, and treatment of neurodegenerative diseases remains elusive. (Source: Urolithins: A Prospective Alternative against Brain Aging (Lei An et al, 6 Sept 2023) For more info on urolithins: Urolithins: a Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota (Rocío García‐Villalba et al, 15 Feb 2022)

Wheat Germ Agglutinin (WGA) -- A lectin that protects wheat from insects, yeast, and bacteria. It is found in whole wheat products. Products such as white bread, remove the wheat germ, and thus contain no wheat germ agglutinin. WGA acts like insulin, binding to the insulin receptor sites on cells, thereby blocking the action of insulin. This blocks glucose from nourishing muscles, causes weight gain and insulin resistance. The brain is also dense in insulin receptors particularly in the Hippocampus (memory center), Amygdala (mood) and Cortex (cognition/executive function).

Terms Starting Numerically

6-MSITC -- 6-(Methylsulfinyl)hexyl isothiocyanate is a compound within the isothiocyanate group of organosulfur compounds. 6-MITC is obtained from cruciferous vegetables, chiefly wasabi. It is a known antioxidant. In vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. (Source: Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica) (Takuhiro Uto et al, 15 Aug 2012).

8,8'-Bieckol -- A polyphenol found in the brown algae Ecklonia cava and Ecklonia kurome (types of seaweed). It has attracted attention as a bioactive ingredient for preventing Alzheimer’s disease (AD). It is anti-inflammatory. For more information on 8,8'-Bieckol see: Investigating the Potential Anti-Alzheimer’s Disease Mechanism of Marine Polyphenols: Insights from Network Pharmacology and Molecular Docking (Kumju Youn et al, 6 Nov 2023). In a 2023 study of healthy older adults aged 60 years and over, the group taking one tablet (0.8 mg of 6-MSITC) every day for 12 weeks showed a significant improvement in working and episodic memory performances. (Source: Benefits of Wasabi Supplements with 6-MSITC (6-Methylsulfinyl Hexyl Isothiocyanate) on Memory Functioning in Healthy Adults Aged 60 Years and Older: Evidence from a Double-Blinded Randomized Controlled Trial (Rui Nouchi et al, 30 Oct 2023).

Deeper dive into the science of natural products and health effects

Three areas of particular concern to ApoE4s are Alzheimer’s disease, heart disease, and longevity. This section concentrates solely on Alzheimer’s Disease and brain/cognitive function. Here are some studies showing the positive effects of plant chemicals regarding this area of concern. This is not a complete list, many papers are not represented here, especially those behind paywalls.

Flavonoids and fibrate modulate apoE4-induced processing of amyloid precursor protein in neuroblastoma cells (Viralkumar Davra and Kenza E. Benzeroual, 22 Dec 2023)

Conclusion: Thus, we suggest that fenofibrate, naringenin, and diosmetin treatments can reduce apoE4- induced Aβ production by distinct mechanisms that may prove useful in developing drugs for AD patients.

Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial (Chirag M Vyas et al, 7 Dec 2023) This randomized clinical trials (RCT) tested the effects of cocoa extract, a source of flavanols, on late-life cognition. Daily cocoa extract supplements were found to possibly improve cognitive health among older people consuming a poor-quality diet. The authors observed that cocoa extract resulted in no cognitive benefit for older people who regularly consumed a high quality diet.

Polyherbal and Multimodal Treatments: Kaempferol- and Quercetin-Rich Herbs Alleviate Symptoms of Alzheimer’s Disease (Claire Alexander et al, 20 Nov 2023)

Despite the well-documented pathophysiology of Alzheimer’s Disease (AD), treatment options are limited in diversity and efficacy. Thus, the development of new treatments requires an extensive understanding of molecular pathways altered by drugs in development. In this review, we survey the literature regarding common herbal phytochemicals, kaempferol and quercetin, with a specific focus on their multiple mechanisms that alleviate the pathological underpinnings of AD. Here, we utilize the well-documented mechanisms of quercetin to propose a novel multimodal mechanism of kaempferol, and we discuss common herbal sources and the limitations of these potential treatments.

Comprehensive Review of Nutraceuticals against Cognitive Decline Associated with Alzheimer’s Disease (Edwin E. Reza-Zaldívar and Daniel A. Jacobo-Velázquez, 20 Sep 2023)

Nowadays, nutraceuticals are being incorporated into functional foods or used as supplements with nonpharmacological approaches in the prevention and management of several illnesses, including age-related conditions and chronic neurodegenerative diseases. Nutraceuticals are apt for preventing and treating such disorders because of their nontoxic, non-habit-forming, and efficient bioactivities for promoting neurological well-being due to their ability to influence cellular processes such as neurogenesis, synaptogenesis, synaptic transmission, neuro-inflammation, oxidative stress, cell death modulation, and neuronal survival. The capacity of nutraceuticals to modify all of these processes reveals the potential to develop food-based strategies to aid brain development and enhance brain function, prevent and ameliorate neurodegeneration, and possibly reverse the cognitive impairment observed in Alzheimer’s disease, the most predominant form of dementia in the elderly. The current review summarizes the experimental evidence of the neuroprotective capacity of nutraceuticals against Alzheimer’s disease, describing their mechanisms of action and the in vitro and in vivo models applied to evaluate their neuroprotective potential.

Unveiling the Therapeutic Potentials of Mushroom Bioactive Compounds in Alzheimer’s Disease(Na Li et al, 7 Aug 2023)

Mushrooms, esteemed globally for their exquisite flavors and abundant nutritional benefits, also hold a wealth of health-promoting compounds that contribute to improving AD health. These compounds encompass polysaccharides, proteins, lipids, terpenoids, phenols, and various other bioactive substances. Particularly noteworthy are the potent neuroprotective small molecules found in mushrooms, such as ergothioneine, erinacine, flavonoids, alkaloids, ergosterol, and melanin, which warrant dedicated scrutiny for their therapeutic potential in combating AD. This review summarizes such positive effects of mushroom bioactive compounds on AD, with a hope to contribute to the development of functional foods as an early dietary intervention for this neurodegenerative disease.

Potential Beneficial Effects and Pharmacological Properties of Ergosterol, a Common Bioactive Compound in Edible Mushrooms(Panthakarn Rangsinth et al, 29 June 2023)

Ergosterol is an important sterol commonly found in edible mushrooms, and it has important nutritional value and pharmacological activity. Ergosterol is a provitamin. It has been well established that edible mushrooms are an excellent food source of vitamin D2 because ergosterol is a precursor that is converted to vitamin D2 under ultraviolet radiation. The pharmacological effects of ergosterol, which include antimicrobial, antioxidant, antimicrobial, anticancer, antidiabetic, anti-neurodegenerative, and other activities, have also been reported. This review aims to provide an overview of the available evidence regarding the pharmacological effects of ergosterol and its underlying mechanisms of action. Their potential benefits and applications are also discussed.

Impact of Gut Microbiota in Brain Ageing: Polyphenols as Beneficial Modulators(Fiorella Sarubbo et al, 26 March 2023) This study aimed to compose the existing picture of the gut microbiotas' impact on aging and outline how polyphenols modulate against brain aging.

The gut microbiota and the brain are bidirectionally communicated via the GBA [gut-brain axis]. This implies that changes in this communication are the causes of the loss or the gain of brain homeostasis and, consequently, they have an impact on brain ageing. There are extrinsic factors, such as diet, which have the ability to affect this gut–brain connection. Natural components of diet, such as polyphenols, due to their antioxidants and anti-inflammatory properties, have been highlighted as modulators of brain ageing, one of the ways being the regulation of gut microbiota and the GBA. Numerous studies in animals and some in humans have shown these favourable effects of polyphenols on brain ageing via the gut microbiome and GBA, indicating the need for further research in order to develop therapeutical strategies against ageing based on the oral intake of polyphenols. This topic is an actual and prevailing research line, focusing on the prevention of brain ageing.

Turning Back the Clock: A Retrospective Single-Blind Study on Brain Age Change in Response to Nutraceuticals Supplementation vs. Lifestyle Modifications(Andrew A. Fingelkurts and Alexander A. Fingelkurts, 21 Mar 2023)

In the present study, we aimed to show that BBA [Brain Biological Age] can be decelerated or even reversed in humans (N = 89) by using customized programs of nutraceutical compounds or lifestyle changes (mean duration = 13 months).
Results: We observed that BBA was younger than CA [chronological age] in both groups at the end of the intervention. Furthermore, the BBA of the participants in the nutraceuticals group was 2.83 years younger at the endpoint of the intervention compared with their BBA score at the beginning of the intervention, while the BBA of the participants in the lifestyle group was only 0.02 years younger at the end of the intervention. These results were accompanied by improvements in mental–physical health comorbidities in both groups. The pre-intervention BBA score and the sex of the participants were considered confounding factors and analyzed separately.

Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer’s disease(Printha Wijesinghe et al, 14 Mar 2023)

In this work, using the data from both planes of section (wholemount neuroretina vs. retinal cross-section), we explored the possible underlying mechanism of dietary antioxidant ergothioneine against Aβ accumulation in a transgenic 5XFAD mouse model. On the whole, despite the small sample size, significantly depleted astrocytes in 5XFAD mice compared with WT controls suggests lack of glymphatic drainage, a macroscopic waste clearance system mediated by astrocytic end-feet in the retinas of 5XFAD mice. Whereas improved Aβ clearance in Ergo-treated 5XFAD compared with non-treated 5XFAD supports our concept that Ergo stimulates Aβ clearance possibly by phagocytic IBA1(+)ve blood-derived macrophages and via perivascular drainage.

Carotenoids: Role in Neurodegenerative Diseases Remediation(Kumaraswamy Gandla et al, 8 March 2023)

Carotenoids, often known as “CTs”, are pigments that exist naturally and play a vital role in the prevention of several brain illnesses. CTs are organic pigments with major significance in ND prevention. More than 600 CTs have been discovered in nature, and they may be found in a wide variety of creatures. Different forms of CTs are responsible for the red, yellow, and orange pigments seen in many animals and plants. Because of their unique structure, CTs exhibit a wide range of bioactive effects, such as anti-inflammatory and antioxidant effects. The preventive effects of CTs have led researchers to find a strong correlation between CT levels in the body and the avoidance and treatment of several ailments, including NDs. To further understand the connection between OS, neuroinflammation, and NDs, a literature review has been compiled. In addition, we have focused on the anti-inflammatory and antioxidant properties of CTs for the treatment and management of NDs.

Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory (Ramón Martínez-Mármol, 20 January 2023) Hericerin is found in the Hericium erinaceus mushroom, aka Lion's Mane.

Here we demonstrate that crude and purified extracts of the nootropic mushroom H. erinaceus have BDNF-like neurotrophic activity both in cultured hippocampal neurons and in paradigm models of learning in vivo, leading to marked neurite outgrowth and improved memory.

Phytochemicals and Antioxidant Properties of Edible Flowers(Panagiotis Kandylis, 2 October 2022)

Edible flowers have been used throughout the centuries for their pharmaceutical properties, but also in some areas for culinary purposes. There is a great variety of edible flowers, and numerous studies are available regarding their chemical composition and potential antioxidant and functional characteristics. Therefore, the present work focuses on gathering a vast amount of data regarding edible flowers. Phytochemical content, total phenolic content, total flavonoid content and antioxidant activity (DPPH, FRAP, ABTS, etc.) of more than 200 edible flowers are presented. The main phytochemicals belong to the groups of phenolic acids, flavonoids, carotenoids and tocols, while great variability is reported in their content. The present study could be a useful tool to select the edible flowers that can be served as sources of specific phytochemicals with increased antioxidant activity and evaluate them for their safety and potential application in food industry, during processing and storage.

Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (Javad Sharifi-Rad et al, 15 Sep 2022)

This article presents the current state of Alzheimer’s research, the pharmacological proposals, and the various studies with phytochemicals, from the point of view analytical and critical, highlighting the advantages and possible limitations. The nanoformulations section offers a perspective on the impact of new formulations and the advent of new technologies to aid phytochemical treatment.

The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease (Yanshree et al, 24 Jul 2022)

Researchers have been investigating Hericium erinaceus, or the monkey head mushroom [also known as lion’s mane], an edible medicinal mushroom, as a possible treatment for AD. In this narrative review, we evaluated six preclinical and three clinical studies of the therapeutic effects of Hericium erinaceus on AD. Preclinical trials have successfully demonstrated that extracts and bioactive compounds of Hericium erinaceus have potential beneficial effects in ameliorating cognitive functioning and behavioral deficits in animal models of AD.

Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes(Ilaria Piccialli et al, 4 May 2022)

Intriguingly, many plant-derived compounds have proven their efficacy in counteracting several pathogenic processes such as the Aβ aggregation, neuroinflammation, oxidative stress and insulin resistance. Many strategies have also been conceived to overcome the limitations of some promising phytochemicals related to their poor pharmacokinetic profiles, including nanotechnology and synthetic routes. Considering the emerging therapeutic potential of natural medicine, the aim of the present review is therefore to highlight the most promising phytochemical compounds belonging to two major classes, polyphenols and monoterpenes, and to report the main findings about their mechanisms of action relating to the AD pathogenesis.

Plant Terpenoids as the Promising Source of Cholinesterase Inhibitors for Anti-AD Therapy(Shereen Lai Shi Min et al, 14 Feb 2022)

Plant-derived terpenes have been a research interest in the recent years, as they are believed to possess the ability to function as a cholinesterase inhibitor. As the deficit of cholinergic activity is one of the factors that causes cognitive impairment in Alzheimer’s disease patients, it serves as a great therapeutic target. It has been found that various terpenoids, such as diterpenoids, triterpenoids and sesquiterpenoids, do have the ability to inhibit cholinesterase activity, and their chemical structures do play a role in this. As terpenoids possess anti-cholinesterase properties, it is encouraged to have future research on drug discovery and development in treating Alzheimer’s disease.

Natural Products as Novel Neuroprotective Agents; Computational Predictions of the Molecular Targets, ADME Properties, and Safety Profile(Sahar Saleh Alghamdi, 20 Jan 2022)

Neurodegenerative diseases (NDs) are one of the most challenging public health issues. Despite tremendous advances in our understanding of NDs, little progress has been made in establishing effective treatments. Natural products may have enormous potential in preventing and treating NDs by targeting microglia; yet, there have been several clinical concerns about their usage, primarily due to a lack of scientific evidence for their efficacy, molecular targets, physicochemical properties, and safety. ... After screening 54 neuroprotective phytochemicals, our findings suggest that Aromatic-turmerone, Apocynin, and Matrine are the most promising compounds that could be considered when designing novel neuroprotective agents to treat neurodegenerative diseases via modulating microglial polarization.

Carotenoid-Rich Brain Nutrient Pattern Is Positively Correlated With Higher Cognition and Lower Depression in the Oldest Old With No Dementia(Jirayu Tanprasertsuk et al, 29 Jun 2021)

Both multivariate and univariate analyses demonstrate that brain nutrient pattern explained mainly by carotenoid concentrations is correlated with cognitive function among subjects who had no dementia. Investigation of their synergistic roles on the prevention of age-related cognitive impairment remains to be performed.

Therapeutic applications of mushrooms and their biomolecules along with a glimpse of in silico approach in neurodegenerative diseases (Sachchida Nand Rai et al, May 2021)

  • Edible mushrooms show very potent Anti-oxidative and Anti-inflammatory activity.
  • Biomolecules of mushrooms show a prominent therapeutic response against lifestyle-related diseases.
  • Mushrooms also widely utilize to manage neurodegenerative diseases like Parkinson’s and Alzheimer’s disease.
  • The biomolecules of mushrooms also exhibit strong therapeutic properties.

Neuroprotective Natural Products for Alzheimer’s Disease (Xin Chen et al, 25 May 2021)

A wide variety of natural products from different origins have been evaluated preclinically and clinically for their neuroprotective mechanisms in preventing and attenuating the multifactorial pathologies of AD. This review mainly focuses on the possible neuroprotective mechanisms from natural products that may be beneficial in AD treatment and the natural product mixtures or extracts from different sources that have demonstrated neuroprotective activity in preclinical and/or clinical studies. It is believed that natural product mixtures or extracts containing multiple bioactive compounds that can work additively or synergistically to exhibit multiple neuroprotective mechanisms might be an effective approach in AD drug discovery.

Neuroprotective Herbs for the Management of Alzheimer’s Disease(Julie Gregory et al, 8 Apr 2021)

Methods—This article systematically reviews recent studies that have investigated the role of neuroprotective herbs and their bioactive compounds for dementia associated with Alzheimer’s disease and pre-Alzheimer’s disease. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter. Conclusions—Medicinal plants have great potential as part of an overall program in the prevention and treatment of cognitive decline associated with AD. It is hoped that these medicinal plants can be used in drug discovery programs for identifying safe and efficacious small molecules for AD.

Citrus Polyphenols in Brain Health and Disease: Current Perspectives (Matthew G. Pontifex et al, 19 Feb 2021)

In this review, we will examine the current evidence on polyphenols and their effects on brain health, focusing specifically on citrus polyphenols since these are one of the main groups of flavonoids in the European diet.

Insights into the role of diet and dietary flavanols in cognitive aging: results of a randomized controlled trial(Richard P. Sloan et al, 15 Feb 2021)

With the world's population aging, age-related memory decline is an impending cognitive epidemic. Assessing the impact of diet on cognitive aging, we conducted a controlled, randomized, parallel-arm dietary intervention with 211 healthy adults (50–75 years) investigating effects of either a placebo or 260, 510 and 770 mg/day of cocoa flavanols for 12-weeks followed by 8-weeks washout. The primary outcome was a newly-developed object-recognition task localized to the hippocampus’ dentate gyrus. Secondary outcomes included a hippocampal-dependent list-learning task and a prefrontal cortex-dependent list-sorting task. The alternative Healthy Eating Index and a biomarker of flavanol intake (gVLM) were measured. In an MRI substudy, hippocampal cerebral blood volume was mapped. Object-recognition and list-sorting performance did not correlate with baseline diet quality and did not improve after flavanol intake. However, the hippocampal-dependent list-learning performance was directly associated with baseline diet quality and improved after flavanol intake, particularly in participants in the bottom tertile of baseline diet quality. In the imaging substudy, a region-of-interest analysis was negative but a voxel-based-analysis suggested that dietary flavanols target the dentate gyrus. While replication is needed, these findings suggest that diet in general, and dietary flavanols in particular, may be associated with memory function of the aging hippocampus and normal cognitive decline.

Dietary flavanols improve cerebral cortical oxygenation and cognition in healthy adults(Gabriele Gratton et al, 24 Nov 2020)

Cocoa flavanols protect humans against vascular disease, as evidenced by improvements in peripheral endothelial function, likely through nitric oxide signalling. Emerging evidence also suggests that flavanol-rich diets protect against cognitive aging, but mechanisms remain elusive. In a randomized double-blind within-subject acute study in healthy young adults, we link these two lines of research by showing, for the first time, that flavanol intake leads to faster and greater brain oxygenation responses to hypercapnia, as well as higher performance only when cognitive demand is high. Individual difference analyses further show that participants who benefit from flavanols intake during hypercapnia are also those who do so in the cognitive challenge. These data support the hypothesis that similar vascular mechanisms underlie both the peripheral and cerebral effects of flavanols. They further show the importance of studies combining physiological and graded cognitive challenges in young adults to investigate the actions of dietary flavanols on brain function.

Long-Term Intake of Dietary Carotenoids Is Positively Associated with Late-Life Subjective Cognitive Function in a Prospective Study in US Women(Changzheng Yuan et al, July 2020)

Our findings support a long-term beneficial role of carotenoid consumption on cognitive function in women.

Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort (Esra Shishtar et al, 22 Apr 2020)

Our findings imply that higher long-term dietary intakes of flavonoids are associated with lower risks of ADRD [Alzheimer disease and related dementias] and AD [Alzheimer’s Disease] in US adults.

Dietary flavonols and risk of Alzheimer dementia (Thomas M. Holland et al, 21 Apr 2020) from the paper: Isorhamnetin, kaempferol, and myricetin were the most significant flavonol constituents and were found to be associated with a reduction of 38%, 50%, and 38%, respectively, in the rate of incident of Alzheimer disease, for those in the fifth vs first quintile of intake.

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis (V. Prakash Reddy et al, 31 January 2020)

This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.

Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer’s Disease and Parkinson’s Disease(Akira Nakajima and Yasushi Ohizumi, Jul 2019)

In the course of our survey of substances from natural resources having anti-dementia and neuroprotective activity, we found nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin improved cognitive deficits and the pathological features of AD, such as Aβ pathology, hyperphosphorylation of tau, and oxidative stress, in animal models of AD. In addition, nobiletin improved motor and cognitive deficits in PD animal models. These observations suggest that nobiletin has the potential to become a novel drug for the treatment and prevention of neurodegenerative diseases such as AD and PD.

Phytochemicals and cognitive health: Are flavonoids doing the trick? (Ioannis Bakoyiannis et al, Jan 2019)

•Flavonoids constitute a group of polyphenols with numerous effects on behaviour and cognition.
•Flavonoids affect various pathways that are implicated in neuronal proliferation and survival, including the ERK/CREB/BDNF and PI3K/Akt.
•Flavonoids reduce neuroinflammation and oxidative stress and seem to reverse symptoms associated with Alzheimer’s disease.
•Flavonoids enhance cognitive function at a behavioural level and attenuate cognitive decline promoted by brain disorders.

Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study—a randomized controlled trial (Daniela Mastroiacovo et al, 17 Dec 2014)

Conclusions: This dietary intervention study provides evidence that regular CF [cocoa flavanols] consumption can reduce some measures of age-related cognitive dysfunction, possibly through an improvement in insulin sensitivity. These data suggest that the habitual intake of flavanols can support healthy cognitive function with age.

Nutrients and bioactives in green leafy vegetables and cognitive decline (Martha Clare Morris et al, 15 Jun 2018)

Conclusions. Consumption of approximately 1 serving per day of green leafy vegetables and foods rich in phylloquinone, lutein, nitrate, folate, α-tocopherol, and kaempferol may help to slow cognitive decline with aging.

Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer’s disease and Alzheimer-linked pathologies: modulation by nutritional mushrooms (Angela Trovato Salinaro et al, 14 Feb 2018)

Herein, we discuss cellular mechanisms underlying AD neuroinflammatory pathogenesis that are contributory to Alzheimer’s disease. We describe endogenous cellular defence mechanism modulation and neurohormesis as a potentially innovative approach to therapeutics for AD and other neurodegenerative conditions that are associated with mitochondrial dysfunction and neuroinflammation. Particularly, we consider the emerging role of the inflammasome as an important component of the neuroprotective network, as well as the importance of Coriolus and Hericium nutritional mushrooms in redox stress responsive mechanisms and neuroprotection.

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview (Rosaliana Libro et al, 21 Apr 2016)

Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required. In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia. In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia. We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.

Phytochemicals That Regulate Neurodegenerative Disease by Targeting Neurotrophins: A Comprehensive Review (Ramu Venkatesan et al, 14 May 2015) (Ramu Venkatesan et al, 14 May 2015)

This review focuses on the phytochemicals and their derivatives that are used to target neurodegenerative diseases by regulating neurotrophins. Accumulating evidence indicates that dietary phytochemicals may prevent or reverse neurodegenerative disease by targeting neurotrophins.