Khellin has been used as an herbal

folk medicine Traditional medicine (also known as indigenous medicine or folk medicine) comprises medical aspects of traditional knowledge that developed over generations within the folk beliefs of various societies, including indigenous peoples, before the ...

, with use in the Mediterranean dating back to Ancient Egypt, to treat a variety of maladies including:

renal colic Renal colic is a type of abdominal pain commonly caused by obstruction of ureter from dislodged kidney stones. The most frequent site of obstruction is the vesico-ureteric junction (VUJ), the narrowest point of the upper urinary tract. Acute ob ...

kidney stones Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...

coronary disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves Ischemia, the reduction of blood flow to the myocardium, heart muscle due to build-up o ...

bronchial asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coug ...

vitiligo Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmen ...

, and

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

. It is a major constituent of the plant ''

Ammi visnaga ''Visnaga daucoides'' is a species of flowering plant in the carrot family known by many common names, including toothpick-plant, toothpickweed, bisnaga, khella, or sometimes bishop's weed. It is native to Europe, Asia, and North Africa, but it ...

'', also known as Bishop's Weed. Once purified, khellin exists as colorless, odorless, bitter-tasting needle-shaped crystals and is classified as a gamma-pyrone, a

furanochromone Furanochromone is a chemical compound which is a derivative of chromone (1,4-benzopyrone) and furan. Some chemical derivatives of furanochromone show strong interaction with DNA. Furanochromones can be produced in callus cultures of ''Ammi visna ...

derivative. In the early 20th century, researchers searched for khellin analogs with lower

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

and better

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...

. A number of drugs were discovered through this research, such as

amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrilla ...

and

cromolyn sodium Cromoglicic acid (INN)—also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate—is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. ...

, which are used in current medical practice. Efloxate is also mentioned as analog.

Background

Khellin is found in Egypt, the Middle East, and areas surrounding the Mediterranean. It is a major constituent of the plant ''Ammi Visnaga'', existing between 0.3 and 1.2% in the leaves and seeds. Bishop's Weed is a name given to several species of plants; however, only ''Ammi Visnaga'' contains khellin. Khellin is rarely found in its pure form; instead it is found in Ammi Visnaga or "Khella" extract. As a result, many healing properties have been attributed to Khellin that are actually due to other constituents in the extract. Ammi Visnaga preparations are commercially available and very common; however, the amount of Khellin and other ingredients varies greatly between brands and even batches of the same brand. The extract is commonly found as a tea or in a pill form.

Medical use

Therapeutic use is often not recommended, as the risks often outweigh the benefits. Regardless of this recommendation, Ammi Visnaga is still often used in the Middle East, Egypt, and surrounding areas. Unwanted side effects include dizziness, reversible

cholestatic jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metab ...

, pseudoallergic reaction, and elevated levels of liver enzymes (transaminases and

gamma-glutamyltransferase Gamma-glutamyltransferase (also γ-glutamyltransferase, GGT, gamma-GT, gamma-glutamyl transpeptidase; ) is a transferase (a type of enzyme) that catalyzes the transfer of gamma-glutamyl functional groups from molecules such as glutathione to ...

Vitiligo

Vitiligo is a disease which causes loss of pigmentation in portions of skin. When khellin is applied topically in combination with UVA light, it is able to stimulate

melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...

(cells that produce melanin) in hair follicles for successful treatment of vitiligo. One such method is blister roof transplantation; in which, blisters are formed on an unaffected area and are then grafted onto a vitiligo affected area. When khellin is applied topically and treated with UV light, pigmentation returns to treated areas. When taken systemically, khellin induces elevated liver enzyme levels and broad photosensitivity; however, topical application reduces these side effects.

Psoralens Psoralen (also called psoralene) is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered ...

are commonly used for vitiligo treatment, but have higher phototoxic and DNA mutagenic effects. While Khellin treatment in conjunction with UV therapy is successful, accelerated photoaging and increased risk of skin cancer is another concern.

Kidney stones

When ammi visnaga extract is taken daily, as a tea or as a pill,

calcium oxalate Calcium oxalate (in archaic terminology, oxalate of lime) is a calcium salt of oxalic acid with the chemical formula . It forms hydrates , where ''n'' varies from 1 to 3. Anhydrous and all hydrated forms are colorless or white. The monohydrate ...

kidney stone Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...

formation is inhibited, making it a good treatment for

hyperoxaluria Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Bird's disease, after Golding Bird, who first described the condition. Causes Hyperoxaluri ...

(a condition in which there is excessive oxalate excretion in the urine, causing kidney stones). Khellin was thought to slow or prevent calcium oxalate nucleation, preventing stones from forming. However, studies have shown that khellin is not the active ingredient in Ammi Visnaga extract. Upon studying calcium oxalate nucleation, ammi visnaga extract as a whole was shown to prolong nucleation time as well as change stone conformation, while khellin alone had no effect. Khellin has also been used to treat renal colic, which is due mostly to

schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody s ...

infections and

stone In geology, rock (or stone) is any naturally occurring solid mass or aggregate of minerals or mineraloid matter. It is categorized by the minerals included, its Chemical compound, chemical composition, and the way in which it is formed. Rocks ...

formation. The plant mixture had

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...

properties that were seen to relieve renal colic by relaxing the

ureter The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...

and acting as a

Other

Intramuscular injections of khellin can also be used to treat asthma. Khellin acts as a bronchodilator; however, the common side effects including nausea present difficulties. Khellin has been used to relieve the pain associated with

angina pectoris Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of obstru ...

by acting as a selective coronary vasodilator. This can be done either orally or intramuscularly; however nausea is a major side effect regardless of how the medication is taken.

References

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External links

Khellin in the chemexper.net databaseAnimated 3D model
Furanochromones Hydroxyquinol ethers Benzofuran ethers at the benzene ring