Medically reviewed on April 12, 2018
Scientific Name(s): Ammi majus L. and Ammi visnaga Lam. Family: Apiaceae (carrots)
Common Name(s): Ammi , visnaga , khella , khellin
Khella has been used for the treatment of urologic, dermatologic, and respiratory symptoms. It is used in the management of bronchial asthma and angina pectoris. The plant also possesses antimicrobial activity and inhibits certain mutagens. However, research reveals no clinical data regarding the use of khella for any of these conditions. Current research focuses on the use of khellin in the treatment of vitiligo.
The pure compound khellin has been applied topically as a 2% preparation for vitiligo. In a study of cholesterol regulation, khellin 200 mg/day was administered orally.
Contraindications have not yet been identified.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
None well documented.
Nausea, vomiting, and ophthalmic changes (eg, decreased visual acuity) have occurred.
The use of oral khellin is limited by toxicity (eg, elevated liver enzymes, phototoxicity, dermatitis).
This annual plant grows to approximately 120 cm in height, primarily in Egypt, other regions of the Middle East, and the Mediterranean. A. visnaga has been naturalized to parts of the southeastern US. It has a slightly aromatic odor and a very bitter taste. The products of ammi consist of the dried ripe fruits, typically of A. visnaga .
The plant has been cultivated for hundreds of years and was known by the Assyrians. A. majus was cultivated for the cut-flower trade. Both species have been used medicinally. These plants have been used in traditional medicine for millennia, particularly for the management of angina and respiratory diseases. Portions of the plant are made into toothpicks. 1 The fruits have been used in Egyptian folk medicine as diuretics and for the treatment of kidney and bladder stones. 2 Khella also has been used for the traditional management of diabetes in Israel. 3
A. visnaga contains coumarins and furocoumarins (psoralens), the most important of which are khellin and visnagin. Khellin is present in fruits in a concentration of approximately 1% and visnagin in a concentration of approximately 0.3%. 4 Biosynthesis of khellin, visnagin, furocoumarin, and visnadin have been investigated. 5 Xanthotoxin (methoxsalen) and ammidin (imperatorin), 2 furocoumarins from khella fruits, have been discovered. 6 Solubility and dissolution studies of khellin also have been described. 7
Numerous reports regarding khella constituents are available evaluating their concentrations at various stages of maturity, 2 , 8 their presence in certain plant parts, 9 and interactions with different plant extracts. 10
Various methods for determination of khella components have been performed including the following: Micro method (khellin and visnagin), 11 thin-layer chromatography separation (khellin and visnagin), 12 spectrometric determination (khellin and bergapten), 13 high-performance liquid chromatography (khellin and visnagin), 4 , 14 and a polarographic method (khellinum in fruits). 15 Improved methods to determine ammi components also have been reported. 16 , 17
Dihydroseselins have been determined from khella fruits and extracts. 18 Genetically transformed khella cultures have been evaluated. 19 In addition, marmesin, ammoidin, and ammidin have been characterized. 20 The fruit contains a small amount (less than 0.03%) of a volatile oil.
Uses and PharmacologyAnimal data
Acting at multiple sites, visnagin inhibited induced contractile responses in rat vascular smooth muscle. 21 Similarly, visnadin demonstrated peripheral and coronary vasodilatory activities in isolated rat vascular smooth muscle. 22Clinical data
In the 1940s and 1950s, khellin was considered a safe vasodilator for the treatment of angina pectoris in doses up to 300 mg daily. 23 Khellin is commercially available in several multi-ingredient European proprietary preparations for oral and parenteral administration as a vasodilator. It is used in the management of bronchial asthma and angina pectoris. 6 The structure of cromolyn sodium, used in the management of allergic respiratory illness, was based on components derived from A. visnaga . 24 Lipophilic extracts from the plant, including the active components visnadin, khellin, and visnagin, exhibited calcium channel-blocking actions, with visnadin being the most active. 25Antimicrobial
Khella extract showed marked antimicrobial activity against gram-positive bacteria and Candida species. 26 Constituent khellin from ammi fruit parts inhibited the mutagenicity of certain promutagens in Salmonella typhimurium . 27Animal data
Research reveals no animal data regarding the use of khella as an antimicrobial.Clinical data
Research reveals no clinical data regarding the use of khella as an antimicrobial.Vitiligo
Interest in khellin as an adjunct to ultraviolet (UV) light therapy in the treatment of vitiligo is based on the structural similarity between khellin and the psoralens. 28 Success has been reported using oral and topical khellin in clinical studies, 23 , 29 , 30 and a mechanism of action has been studied in cultured human cells. 31Clinical data
Studies using oral (100 mg 23 ) or topical khellin (0.005% encapsulated in liposomes 30 and 5% khellin in water/oil emulsion 29 ) plus UVA therapy achieved success rates comparable to those seen with standard psoralen plus UVA (PUVA) therapy.
Topical therapy with the khellin-UVA combination required longer duration to achieve treatment goals but also demonstrated fewer side effects. 29 Follow-up (mean, 40 months) of patients who received oral khellin showed no long-term side effects. 23Other uses
An ethnobotanical survey including 130 respondents reported khella to be 1 of 16 species of Israeli medicinal plants used for diabetes. 3 However, no clinical trials support this hypoglycemic action.
Extracts of A. majus seeds fed to rats with experimentally induced kidney stones showed no beneficial effect in terms of stone passage or size reduction. 32
A combination product containing khella demonstrated spasmolytic activity on guinea pig ileum in 1 report. 33
When given orally, khellin 50 mg 4 times daily increased HDL-cholesterol levels without affecting total cholesterol or triglyceride concentrations. 7
Pure compound khellin has been applied topically as a 2% preparation for vitiligo, 29 and 100 mg was administered orally to vitiligo patients in a study assessing the effectiveness and safety of khellin. 23 In a study of cholesterol regulation, khellin 200 mg/day was administered orally. 34
Information regarding safety and efficacy in pregnancy and lactation is lacking.
None well documented.
A. majus has been associated with the development of severe ophthalmologic changes, particularly pigmentary retinopathy in photosensitized fowl. 35 , 36 In a study of 28 patients, 1 patient (4%) reported a temporary reduction in visual acuity that resolved upon discontinuation of treatment. 23 Patients receiving khella or its extracts should be monitored for ophthalmologic changes.
The furocoumarins (psoralens) may cause photosensitization and dermatitis. 37 One study reports 4 irritant compounds from ammi seeds and evaluates potential for contact dermatitis. 38 In patients who received oral khellin to reduce blood lipids and in a study to treat vitiligo, nausea and vomiting were observed frequently (29% of patients in the vitiligo study). Elevated AST and ALT also were reported during therapy (7% to 14%). 23 , 34
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