Apigenin: a polyphenol that fights cancer

In this Article (Index)

• What is Apigenin?
• Health Properties
• Apigenin's Anticancer Properties
• Side Effects
• Bioavailability
• Apigenin Content in Certain Foods

What is Apigenin?

Apigenin is a Polyphenol

Apigenin, is a bioactive chemical compound produced by plants. It is type of a polyphenol called a flavonoid. Other varieties of polyphenols are the following: Phenolic acids, stilbenes, and lignans.
Polyphenols are formed by six-sided rings made of carbon atoms with more than one alcohol (phenol) or hydroxyl group (OH—), hence their name "poly". They form compounds with two or three of these rings which differ in the position of the hydroxyl group, and the number of them. Some of them, like apigenin, have a ketone (O⚌) group.

Polyphenols are found in fruits, vegetables, grains, bark, roots, flowers, and stems, as well as in certain beverages prepared with them such as tea, beer, cocoa, and wine.

Flavonoids

Flavonoids are a group of polyphenols that have antioxidant, anti-inflammatory, anti-mutagenic, and anti-carcinogenic properties, they also help prevent neurodegenerative diseases.

Flavone

Flavonoids are comprised of different subgroups Flavones, Flavonols, Flavanones, Isoflavonoids, Flavanols or catechins, Anthocyanins, and Chalcones.

Apigenin is a flavone and its chemical name is 4', 5, 7-trihydroxy flavone. The name apigenin is derived from the name Apium, a genus of plants within the Apiaceae family that includes anise, carrot, celery, coriander, cumin, dill, and fennel.

It is also found in many fruits, vegetables, teas, red wine, and beer. It has a low toxicity and is present in different molecular forms, mainly glycones and glycosides.

Chemistry

Apigenin has hydroxyl groups at positions C-5 and C-7 of the A-ring and C-4' of the B-ring.
Pure apigenin is a yellow crystalline powder that is not soluble in water or fats. Its molecular formula is C₁₅H₁₀O₅. (3)

Apigenin molecule's multiple rings, the ketone group, and the multiple hydroxyl groups give it an electron-rich structure which makes it a potent antioxidant, scavenging free radicals. This may give it its antiviral, and anti-inflammatory properties. (5)

Natural apigenin can be found in different chemical forms. It is mainly attached to sugars as glycosides, the most common being the apigenin-7-O-glucoside. It is also present as glucuronide, acetylated and methyl ester forms, acylated varieties, and monomers, dimers, and larger polymers.

Health Properties

Plant preparations containing apigenin have been used in traditional medicines to treat asthma, neuralgia, shingles, and inflammation. (2)

Like all polyphenols, flavonoids, and flavones, apigenin has health-promoting properties. It is an antioxidant, anti-inflammatory, antimutagenic, antiangiogenic, and anticancer agent and it can also stimulate an immune response. (1),(2)

Apigenin's Anticancer Properties

Several studies have shown that apigenin has anti-cancer effects. These act upon cancer cells in multiple ways. It helps reduce the cancer cell proliferation. It also causes them to die; cancer cells usually block the natural process of death programmed into cells, called apoptosis. Apigenin induces apoptosis. (1)

It causes apoptosis by regulating the quantity of some enzymes called caspases that regulate cell death and other cellular compounds that modulate them, such as BAX, Bcl2, and p53.

Apigenin acts upon the "checkpoints" that regulate cell growth and division causing the cancer cells to die. Finally, it promotes autophagy ("self-eating"), where the cells under stress conditions break down and degrade organelles and proteins and use them as a source of molecules to continue living. Autophagy-associated cell death may act as a tumor suppressor, but, once the cancer progresses, autophagy stops cancer cells from dying by inhibiting apoptosis.

It prevents cancer cell migration and invasion and inhibits angiogenesis, which is the development of new blood vessels that nourish the tumors.

Apigenin acts upon other molecular mechanisms used by the body to control cell growth. These include the PI3K/Akt/mTOR signaling pathway, which promotes cell growth and survival; the NF-κB, MAPK, and ERK pathways, which are involved in inflammation, cell survival, and death; and the Wnt/JNK pathway, which controls cell proliferation, migration, and gene expression.

Research suggests that apigenin reduces the risk of certain cancers such as pancreatic, breast, colorectal, liver, lung, cervical, skin, endometrial, ovarian, bladder, hematological, thyroid, and prostate cancers. (3)

A Trial in mice with human prostate cancer grafts showed a reduction in tumor growth, a reduction in Bcl-2, and an increase in BAX, both of which indicate an increase in apoptosis. The mice received oral doses of 20 and 50μg per mouse per day over 8 weeks. In a human being these doses are equivalent to 0.06 - 0.13 g per day of apigenin, roughly the amount found in 1 - 2 tablespoons of dried parsley respectively, or 2.7 - 5.5 kg (6 - 12 lb) of tomatoes.

Another Trial with transgenic mice that develop human prostate cancer (TRAMP mouse model) "exhibited significant decrease in tumor volumes of the prostate as well as completely abolished distant organ metastasis."

Apigenin supplements against cancer?

A 2021 paper (10) investigated the potential of ingesting apigenin as a therapy against cancer, but it found that using natural foods for such a purpose isn't feasible. It mentioned parsley leaf health supplements with a recommended intake of 2 capsules containing 900 mg of parsley equivalent to a daily dose of 40 mg of apigenin. However, this value is "less than 1% of what is needed for a meaningful clinical outcome on cancer cell behavior."

Possible side effects of apigenin

At the levels found in food, apigenin is safe. Even at higher doses, it is also considered safe. Its toxicity is low.

Nevertheless, intentional intakes of apigenin in dietary supplements or a high intake of food containing it can provoke adverse effects such as sleepiness, sedation, digestive issues, and stomach pain, and muscle relaxation.
Topical application can cause skin irritation.
Check with your healthcare provider before taking any supplements even if they are herbal and "natural".

Apigenin can interact with antiplatelet and anticoagulant medications such as Warfarin and Aspirin. It can interact with cyclosporine and certain chemotherapy drugs. (3)

Due to its sedative properties, it might compound the effects of certain sedating medications such as Diazepam. It may act in a similar way to the hormone Oestrogen and, therefore, interfere with certain hormone replacement therapy interventions.

Doses of apigenin of up to 300mg/kg have been used in mice with no overt toxicity.

Bioavailability

The effectiveness and benefits of apigenin can be affected by its poor absorption by the body (bioavailability) which means the body can't use it to the fullest. (4).

Apigenin glycoside is more soluble in water than unmodified apigenin, it is lipophilic and a weak acid which promotes its uptake by the body's cells.

It is also absorbed by the body more easily, which increases its bioavailability. Between 5 and 10% of the apigenin is absorbed in the small intestine. The remaining 90-95% moves on to the colon where it is metabolized by the bacteria of the gut microbiome. They break down the molecule into smaller phenolic byproducts or metabolites that are absorbed by the colon. It is highly likely that these phenolic metabolites provide the health benefits of a diet rich in polyphenols. Roughly 60-65% of the apigenin is absorbed in the colon. Animal studies show that less than 30% of the original intake of apigenin is excreted in the feces. (5).

Radioactive-labeled apigenin fed to rats in a single dose showed that 51% was eliminated in urine, and 12% in feces. It appeared in blood 24 hours after its intake at levels of 1.2%. Other body parts where it was found were the intestine (9.4%), liver (1.2%), kidneys (0.4%), and the rest of the body (24.8%). Half of the apigenin was eliminated within 91.8 hours. This study shows that despite its low bioavailability, it is processed slowly in the body and its accumulation in different tissues may be the reason for its effective chemopreventive effects. (3)

Intake

A study investigating the intake of five flavonoids (quercetin, kaempferol, myricetin, luteolin, and apigenin) in different countries found that they varied from 6 mg/day in Finland to 64 in Japan (13 mg/d in the U.S.) (3). Regarding apigenin, its daily intake ranges from 0.45 to 1.17 mg (4)

Apigenin Content in Certain Foods

The following table shows the apigenin content in some foods, the values are given in milligrams per kilogram (mg/kg) or liter for liquids (mg/l).

Sources: * (6); †(4); ‡ (7); § (8); ¶ (9); þ (3); ∂ (a)

An example of apigenin intake through your diet

Consuming one cup of chopped tomatoes (200 g) (4.84 mg of apigenin), one tablespoon of dry parsley (1.6 g) (72.05 mg of apigenin), 1/2 cup of bell pepper (70 g) (19,04 mg of apigenin), 1/2 cup of red onion (70 g) (2.42 mg of apigenin), glass of red wine (350 ml) (1.8 mg of apigenin), chamomile tea (3 g) (2.1 mg of apigenin). Grand Total: 102.25 mg of apigenin.

Note that almost 3/4 of it came from the parsley.

Closing Comments

Apigenin is a potent bioactive polyphenol. It is found in plant-based foods and has antioxidant, anti-inflammatory, antiviral, anti-cancer, and antimutagenic properties. It also helps modulate the immune system.

A diet rich in vegetables and fruits will also provide a cocktail of other polyphenols that will provide additional health benefits.