Coumarins

Coumarins are non-flavonoids polyphenols, o-hydroxycinnamic acid lactones (also known as 2H-chromen-2-one1,2-benzopyrone. Coumarins are a group of naturally occurring organic compounds, classified as benzopyrones, found in a wide variety of plants. Coumarin is a colourless crystalline solid with a sweet odour resembling the scent of vanilla and a bitter taste.

Coumarins and flavonoids are both polyphenolic compounds found in plants but coumarins are based on a benzopyrone structure, while flavonoids are based on a phenyl-benzopyran structure.

Medicinal properties of coumarins

Coumarins are aromatic and potent substances which have been found to contain anti-carcinogenic compounds and have multi-biological activities such as being anti-arrhythmia, anti-asthma, antibacterial, antifungal, anti-HIV, anti-hypertension, anti-osteoporosis, antiseptic, anti-tumour and pain relieving. Coumarins can also inhibit adipogenesis, which is the process of fat cell (adipocyte) formation.

Coumarins have various other properties, including blood thinning and anticancer effects. They act as an anticoagulant by inhibiting vitamin K epoxide reductase (VKOR), leading to decreased clotting factors II, VII, X, and IX. They also, possess antioxidant and anti-inflammatory properties, but can be toxic at high doses.

Many coumarins and flavonoids are named after the Latin names of the plants that are rich in these components. For example: Cow parsnip (Heracleum lanatum) was found to be rich in a particular furanocoumarin compound and thus this substance was named heraclenin. Likewise aniseed (Pimpinella anisum) was found to contain another kind of furanocoumarin and so this was called pimpinellin.

There are four main classifications of coumarins:

1. Simple coumarins
2. Furanocoumarins
3. Pyrano coumarins
4. Pyrone substituted coumarins

Plant coumarins

• Esculetin (aesculetin)
• Fraxetin
• Daphnetin
• Limettin
• Osthole is found in the Cnidium monnieri plant.
• Scopoletin found in red peppers.
• Seselin
• Xanthyletin

NOTE: Seselin and xanthyletin are prenylated.

Studies have also shown that coumarins function as blood thinning agents and also exhibit anti-fungal properties. Studies have also proved the selective cytotoxicity of coumarins for tumour cells and also the positive effect of coumarins in the regulation of immune response, cell growth and differentiation. They also possess anti-aging, and cardioprotective properties.

Note: Coumarins should not be consumed while taking anticoagulants.

A recent study has shown that 7-hydroxycoumarin inhibits the release of Cyclin D1, which is overexpressed in many types of cancer.

Aesculetin is a derivative of coumarin and found in chicory and genistein is an isoflavone. Both genistein and aesculetin exert a very potent inhibitory effect on cancer cell growth.

Not all coumarin associated derivatives are beneficial to human health. Two examples are dicoumarol and furanocoumarins.

Dicoumarol

Moulds such as Penicillium nigricans, Penicillium jensi and the Aspergillus metabolise coumarin into dicoumarol. Dicoumarol is similar in structure to vitamin K. When consumed by livestock it inhibits vitamin K production. Vitamin K is necessary in the body to activate prothrombin. When tissue is damaged, thromboplastin is released and converts prothronin to thrombin.

Thrombin alters the solubility of fibrinogen in blood and causes it to clot and seal the tissue damage. Dicoumarol prevents this process and is used in blood thinning medications such as warfarin and as pesticides for rats and mice.

NOTE: Dicoumarol can cause significant kidney and liver damage.

Furanocoumarins (furocoumarins)

• Umbelliferone
• Aurapten
• Epoxyaurapten
• Psoralen (aka psoralene)
• 5-hydroxy-xanthotoxin
• 5,8-dihydroxy-psoralen
• 8-hydroxy-bergapten
• 5-geranyloxy-7-methoxycoumarin

Furanocoumarins also consist of three clusters:

1. The bergapten cluster:  bergapten, bergamottin, bergaptol, epoxybergamottin, isoimperatorin, oxypeucedanin, oxypeucedanin hydrate, 6’,7’-dihydroxy-bergamottin.
2. The isopimpinellin cluster: byakangelicin, byakangelicol, cnidicin, cnidilin, isopimpenellin, phellopterin.
3. The xanthotoxin cluster: heraclenin, heracenol, imperatorin, xanathotoxol, xanpothotoxin, 8-gerynaloxy-psoralen.

Furanocoumarins are toxic compounds found primarily in species of the Umbelliferae (Apiaceae) family which includes carrots, celery, cow parsnip and parsley and Rutacea (citrus fruits). They are potent chemical defences that have adverse effects on wide variety of organisms, ranging from bacteria to mammals.

Umbelliferone, also known as 7-hydroxycoumarin, hydrangine, skimmetine and beta-umbelliferone, is also found in aniseed (Pimpinella anisum) and liverwort.

Parsnips (Pastinaca sativa) contain the furanocoumarins bergapten, imperatorin, isopimpinellin and xanthotoxin.

Cow parsnip (Heracleum lanatum) contains apterin, vaginidiol, isobergapten, xanthotoxin (8-methoxypsoralen), umbelliferone, lanatin, pimpinellin, isopimpinellin, coumaric and ferulic acids, bergapten, sphondin, xanthotoxol, psoralen, heraclenin

Parsley contains isobegaptin and parsley and celery contain scopoletin.

Citrus fruits are able to produce defence compounds furanocoumarins to avoid attacks by herbivorous insects and pathogens. In humans, these chemical compounds are strong photosensitisers and can interact with medications, leading to the “grapefruit juice effect”. Citrus species can be separated into four groups that correspond to the four original species (ancestral taxa).

• Citrons
• Mandarins
• Papedas
• Pummelos

Three of the four (pummelos, citrons and papedas) synthesise high amounts of coumarins and furanocoumarins, whereas mandarins are devoid of them.

The genetic origin of the grapefruit is a hybrid mix. One ancestor was the Jamaican sweet orange (Citrus sinensis), itself an ancient hybrid of Asian origin; the other was the Indonesian pomelo (Citrus maxima). This crossbreeding resulted in higher levels of furancoumarins in the grapefruit and is an example of why tampering with natural food crops is not advisable before knowing their complete chemical make-up and the outcome of doing so.

According to new research, it is not the flavonoids in grapefruit that interact dangerously with some drugs as once thought, it is the furanocoumarins. Some medications, such as those for cholesterol and hypertension, are affected by furanocoumarins so that they enter the bloodstream too quickly.

Furanocoumarins influence the function of certain enzymes, along the gastrointestinal tract or in the liver, and these interactions influence the rate at which certain medications can be broken down or removed from the body. Once such medication is felodipine (marketed as Plendil), a drug used for treating hypertension.

When grapefruit juice is consumed, the level of the blood pressure lowering medication in the body becomes as much as five times higher and the blood pressure may fall too low, causing symptoms of light-headedness, dizziness, weakness or even fainting. It does not take much grapefruit or grapefruit juice to make this happen, especially if it is consumed on a regular basis.

Another group of medications that interact with grapefruit are the “statins,” which are now widely prescribed to lower blood cholesterol levels. There are many other medications, however, that also interact with grapefruits. A partial list (using drug generic names) includes the following:

Citrus fruit rinds are the richest source of coumarins. They are also found in certain microorganisms such as novobiocin from Streptomycin and aflatoxin from the Aspergillus species.

Natural sources of coumarins in alphabetical order

Rich plant sources of coumarins

• Cassia cinnamon (Cinnamomum cassia) Not to be confused with true cinnamon (Cinnamomum zeylanicum) which contains little coumarin.
• Cherry blossom tree leaves (of the Prunus genus)
• Clover (Ladino clover sprouts)
• Cnidium monnieri seeds
• Deertongue (Dichanthelium clandestinum)
• Lavender (Lavandula)
• Mullein (Verbascum spp.)
• Red clover (Trifolium pratense)
• Sweet clover (Melilotus sp.)
• Sweet grass (Hierochloe odorata)
• Sweet woodruff (Galium odoratum)
• Tonka bean (Dipteryx odorata),
• Vanilla grass (Anthoxanthum odoratum),
• Water willow (Justicia pectoralis)

Due to their strong aromatic compounds coumarins are used in 90% of perfumes.

NOTE: Richest sources of coumarins are cassia leaf oil, cassia cinnamon bark oil, lavender oil and citrus fruits.

WARNING: Excessive consumption of coumarins may damage the liver and kidneys in some individuals.

Coumestans

Coumestan is a heterocyclic organic compound that is a derivative of coumarin and forms the central core of a variety of natural compounds known collectively as coumestans. These, and isoflavones, flavones, deoxybenzoins and lignans are all classes of phytoestrogens.

Coumestans are oxidation products of pterocarpan and similar to coumarin. Coumestans, including coumestrol, a phytoestrogen, are found in a variety of plants that has oestrogenic activity that is 30 to 100 times greater than that of isoflavones.

Coumestans have been shown to decrease bone resorption and promote the mineralisation of bone. Regular consumption of foods rich in this compound can help treat menopause symptoms and lowers the risk of hip fractures, breast cancer and heart disease.

Natural sources of coumestan in alphabetical order

• Alfalfa sprouts
• Butterbeans
• Clover sprouts
• Soya beans
• Split peas

Health issues coumestans can help to treat

• Breast cancer
• Heart disease
• Hip fractures
• Menopause

Latest research

More flavonoids have been discovered and named by Japanese scientists while studying the Sophora root, Ku shen (Sophora flavescens) plant.

• Formonometin
• Kurarinol
• Kuraridinol
• Neokurarinol
• Nor-kurarinol
• Isokurarinone

The prenylated isoflavone, 8-Prenylkaempferol can also be found in Sophora flavescens.

 They also found new ones in the Sophora augustifolia plant and named them thus:

• Isoanhydroicaritin
• Isoxanthohumol
• Kuraridin
• Kurarinone
• Nor-anhydroicaritin
• Nor-kurarinone
• Xanthohumol

Other phytoestrogens:

• Deoxybenzoins
• Flavones
• Isoflavones
• Lignans

Related subjects

• A-Z of ailments
• A-Z of nutrients
• Flavonoids
• Pain and inflammation

References:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142757

https://www.medicalnewstoday.com/articles/43420.php