by Eric Yarnell, ND, RH(AHG)
Last updated 16 Jan 2022
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Table of Contents
Clinical Highlights
Khella is a moderately-potent smooth muscle spasmolytic.
Khella is generally safe at usual doses (though it can potentially be photosensitizing).
Khella and its close cousin Ammi majus (bishop's weed) are NOT interchangeable.
Khella is generally safe at usual doses (though it can potentially be photosensitizing).
Khella and its close cousin Ammi majus (bishop's weed) are NOT interchangeable.
Ammi visnaga inflorescence (photo copyright E. Yarnell)
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Ammi majus (bishop's weed) inflorescence (photo copyright E. Yarnell)
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Clinical Fundamentals
Part Used:
The fruit (often erroneously labeled the seed) is used medicinally. Though fresh, unripe fruits contain the highest levels of furanocoumarins, harvesting them dry may preserve these constituents better if drying and storage are contemplated (Franchi, et al. 1985).
Taste: sharp, celery-like flavor.
Major Actions:
Khella acts primarily as a smooth muscle relaxant primarily because it is a calcium channel blocker (Duarte, et al. 1997; Ubeda and Villar 1989; Anrep, et al. 1949). Lipophilic extracts of khella were calcium channel antagonists in vitro, with visnadin, khellin, and visnagin being the most active compounds, but only about 10% as potent as verapamil (Rauwald, et al. 1994).
Major Organ System Affinities:
Major Indications:
As a spasmolytic (oral):
As a photosensitizer (oral and/or topical):
Other (oral):
In a case study, a 50-year-old Arab man with multiple 3--5 mm kidney stones cause acute ureteral colic, hypertension, and dyslipidemia was treated with khella fruit 10 g decocted in 200 ml water twice daily for 10 days (Bhagavathula, et al. 2015). He passed all the kidney stones successfully and his HDL cholesterol level rose from 32 to 56 mg/dl with no change in any other serum lipid levels. Clinical studies in Eastern Europe show reduced stone formation and partial dissolution (Modli'nski 1977).
Numerous clinical studies confirm the efficacy of oral khella + sunlight exposure or UVA/B phototherapy in treating autoimmune diseases of the skin, notably vitiligo and psoriasis. In a randomized, double-blind trial, 60 patients with vitilgo took 100 mg khellin once daily or placebo, followed 45 min later by 15 min of sun exposure (in Egypt) (Abdel-Fattah, et al. 1982). After 4 mon, 40% of patients taking khella had 50% or greater repigmentation compared to no repigmentation in the placebo group. Results were durable for 1 year. A similarly executed trial in Egyptian patients with psoriasis found that 6 of 8 had a significant response to therapy compared to none of the 10 subjects randomized to placebo after 4 months, and results were durable to 3 years in the treatment group (Abdel-Fattah, et al. 1983). In one open trial, oral kehllin + L-phenylalanine in phosphatidylcholine liposomes (dose unknown) was combined with UVA/B and compared to UVA/B alone in 74 Dutch vitiligo patients (de Leeuw, et al. 2003). There was dramatic repigmentation in the vitiligo group over 12 months, with 75% or greater repigmentation of the face in 63% of participants in particular. Phototherapy by itself had almost no benefit. There were no cases of photodermatitis in this cohort.
Note that that the anti-allergy and anti-asthma drug cromolyn was derived from khellin originally (Meyer 2002).
Major Constituents:
The fruit (often erroneously labeled the seed) is used medicinally. Though fresh, unripe fruits contain the highest levels of furanocoumarins, harvesting them dry may preserve these constituents better if drying and storage are contemplated (Franchi, et al. 1985).
Taste: sharp, celery-like flavor.
Major Actions:
- Spasmolytic (smooth muscle relaxer) (Rauwald, et al. 1994; Ubeda and Villar 1989)
- Bronchodilating (Hauviller and Asrilant 1955; Kennedy and Stock 1952)
- Coronary artery dilator (Sternieri, et al. 1961; Velazquez, et al. 1961; Uhlenbroock and Schweer 1960; Farrand and Horvath 1959; Schmidt 1958; Anrep, et al. 1949)
- Photosensitizing, topical autoimmune inhibitor (Vedaldi, et al. 1988)
- Stimulates melanin production (Carlie, et al. 2003)
- Inhibits calcium oxalate crystallization (Kachkoul, et al. 2018)
Khella acts primarily as a smooth muscle relaxant primarily because it is a calcium channel blocker (Duarte, et al. 1997; Ubeda and Villar 1989; Anrep, et al. 1949). Lipophilic extracts of khella were calcium channel antagonists in vitro, with visnadin, khellin, and visnagin being the most active compounds, but only about 10% as potent as verapamil (Rauwald, et al. 1994).
Major Organ System Affinities:
- Lower respiratory tract
- Cardiovascular system
Major Indications:
As a spasmolytic (oral):
- Asthma (Kennedy and Stock 1952; Chrysanthis 1950)
- Angina pectoris (Nalefski, et al. 1952; Conn, et al. 1952; Hultgren, et al. 1952; Osher, et al. 1951; Armbrust and Levine 1950; Dewar and Grimson 1950; Anrep, et al. 1949 and 1946; Kenawy and Barsoum 1945)
- Benign prostatitis hyperplasia, spasmodic type (does not treat underlying hyperplasia) (Yarnell 2018)
- Gallbladder spasm
- Intestinal colic
- Ureteral colic, acute (Bhagavathula, et al. 2015)
As a photosensitizer (oral and/or topical):
- Psoriasis, topical and oral (Abdel-Fattah, et al. 1983)
- Vitiligo, topical and oral (Fenniche, et al. 2018; de Leeuw, et al. 2003; Ortonne 1998; Orecchia, et al. 1998; Abdel-Fattah, et al. 1982)
Other (oral):
- Urolithiasis, prevention and dissolution (Charafi, et al. 2012; Khan, et al. 2001;Modli'nski 1977)
In a case study, a 50-year-old Arab man with multiple 3--5 mm kidney stones cause acute ureteral colic, hypertension, and dyslipidemia was treated with khella fruit 10 g decocted in 200 ml water twice daily for 10 days (Bhagavathula, et al. 2015). He passed all the kidney stones successfully and his HDL cholesterol level rose from 32 to 56 mg/dl with no change in any other serum lipid levels. Clinical studies in Eastern Europe show reduced stone formation and partial dissolution (Modli'nski 1977).
Numerous clinical studies confirm the efficacy of oral khella + sunlight exposure or UVA/B phototherapy in treating autoimmune diseases of the skin, notably vitiligo and psoriasis. In a randomized, double-blind trial, 60 patients with vitilgo took 100 mg khellin once daily or placebo, followed 45 min later by 15 min of sun exposure (in Egypt) (Abdel-Fattah, et al. 1982). After 4 mon, 40% of patients taking khella had 50% or greater repigmentation compared to no repigmentation in the placebo group. Results were durable for 1 year. A similarly executed trial in Egyptian patients with psoriasis found that 6 of 8 had a significant response to therapy compared to none of the 10 subjects randomized to placebo after 4 months, and results were durable to 3 years in the treatment group (Abdel-Fattah, et al. 1983). In one open trial, oral kehllin + L-phenylalanine in phosphatidylcholine liposomes (dose unknown) was combined with UVA/B and compared to UVA/B alone in 74 Dutch vitiligo patients (de Leeuw, et al. 2003). There was dramatic repigmentation in the vitiligo group over 12 months, with 75% or greater repigmentation of the face in 63% of participants in particular. Phototherapy by itself had almost no benefit. There were no cases of photodermatitis in this cohort.
Note that that the anti-allergy and anti-asthma drug cromolyn was derived from khellin originally (Meyer 2002).
Major Constituents:
- Furanocoumarins (particularly khellin, visnadin(e), and visnagin) (Bishr, et al. 2016; Kamal, et al. 2015; Badr, et al. 2015; el-Domiaty 1992; Karawya, et al. 1970)
- Terpenoids
Khellin
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Visnadine
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Adverse Effects:
Khella can theoretically cause a photosensitivity skin rash. There are no published case reports of this ever happening, and the author has seen no cases in his practice. Khella's close cousin Ammi majus (bishop's weed) can very readily cause phytophotodermatitis with several published cases in the literature (Alouani, et al. 2018; Ossenkoppele, et al. 1991). In young geese, only bishop's weed fruit induced photosensitivity, while feeding them any part of khella did not (Shlosberg, et al. 1974). Most research suggests khellin is a weak photosensitizer and does not induce significant numbers of cross-strand DNA linking, thus it is unlikely to be carcinogenic (Morliere, et al. 1988; Vedaldi, et al. 1988).
t is prudent to recommend that patients who are taking khella orally take simple precautions against excessive sun exposure, and that those using it intentionally as a topical photosensitizer limit the duration of sun exposure (see pharmacy essentials below for more information).
Oral khella can occasionally cause an upset stomach. Even large doses of pure khellin (up to 150 mg qd po) have caused only minor adverse effects in a small number of patients, mostly nausea, anorexia, dizziness, and occasionally rebound bronchospasm (Nalefski, et al. 1952).
There is one case study reported in the literature of a 67-year-old Egyptian man with type 2 diabetes mellitus, hypertension, and chronic kidney disease stage 3b who developed acute renal after "drinking a bottle of boiled khella seeds" every day for 7–10 days (Al-Shoukabi, et al. 2020). He completely recovered after a course of steroids. Kidney biopsy revealed eosinophilic tubulointerstitial nephritis and acute tubular injury (as well as glomerulosclerosis and other signs of chronic kidney issues).
Khella can theoretically cause a photosensitivity skin rash. There are no published case reports of this ever happening, and the author has seen no cases in his practice. Khella's close cousin Ammi majus (bishop's weed) can very readily cause phytophotodermatitis with several published cases in the literature (Alouani, et al. 2018; Ossenkoppele, et al. 1991). In young geese, only bishop's weed fruit induced photosensitivity, while feeding them any part of khella did not (Shlosberg, et al. 1974). Most research suggests khellin is a weak photosensitizer and does not induce significant numbers of cross-strand DNA linking, thus it is unlikely to be carcinogenic (Morliere, et al. 1988; Vedaldi, et al. 1988).
t is prudent to recommend that patients who are taking khella orally take simple precautions against excessive sun exposure, and that those using it intentionally as a topical photosensitizer limit the duration of sun exposure (see pharmacy essentials below for more information).
Oral khella can occasionally cause an upset stomach. Even large doses of pure khellin (up to 150 mg qd po) have caused only minor adverse effects in a small number of patients, mostly nausea, anorexia, dizziness, and occasionally rebound bronchospasm (Nalefski, et al. 1952).
There is one case study reported in the literature of a 67-year-old Egyptian man with type 2 diabetes mellitus, hypertension, and chronic kidney disease stage 3b who developed acute renal after "drinking a bottle of boiled khella seeds" every day for 7–10 days (Al-Shoukabi, et al. 2020). He completely recovered after a course of steroids. Kidney biopsy revealed eosinophilic tubulointerstitial nephritis and acute tubular injury (as well as glomerulosclerosis and other signs of chronic kidney issues).
"Their [khellin & visnadine] toxicity is extremely low and there are practically no side effects,
even with long-term use." —Weiss 2001
even with long-term use." —Weiss 2001
Contraindications:
There are no definitive contraindications to use of khella. Excessive bright sun exposure (sufficient to cause sun burning) is unwise while using this product due to the low risk of the herb increasing burning.
There is no high-quality information available on the safety of khella in pregnancy or lactation. While it is unlikely to be a problem in either situation, it should only be used if absolutely necessary until more information is available. Topical use in particular is unlikely to be harmful. Very large doses of isolated visnadine produced no harms when given to pregnant rats (Erbring, et al. 1967).
Adverse Drug Interactions:
Combination of khella with other photosensitizing drug such as the methoxylpsoralens is not advisable, though there are no published reports of their interactions.
There are no other known or suspected drug interactions.
There are no definitive contraindications to use of khella. Excessive bright sun exposure (sufficient to cause sun burning) is unwise while using this product due to the low risk of the herb increasing burning.
There is no high-quality information available on the safety of khella in pregnancy or lactation. While it is unlikely to be a problem in either situation, it should only be used if absolutely necessary until more information is available. Topical use in particular is unlikely to be harmful. Very large doses of isolated visnadine produced no harms when given to pregnant rats (Erbring, et al. 1967).
Adverse Drug Interactions:
Combination of khella with other photosensitizing drug such as the methoxylpsoralens is not advisable, though there are no published reports of their interactions.
There are no other known or suspected drug interactions.
Pharmacy Essentials
Tincture: 1:2 to 1:3 w:v ratio, 50–60% ethanol
Dose:
Acute, adult: 1–3 ml up to q2h, adjusted for body size and sensitivities
Chronic, adult: 1–3 ml qd to tid
Child: as adult but adjusted for body size
For BPH or other conditions causing spasms at night, the last dose should be taken at bedtime.
For use for autoimmune skin diseases, follow at least one daily dose 45 min later with 15 min sunshine or UVA/B therapy.
Topical use: apply tincture liberally to vitiligo or psoriasis patches, them cover surrounding areas with sunscreen. Apply UVA or UVB light 45 min after application twice a week or go out into direct sunshine for 15 min. UVB dose: 308 nm Excilite laser 240 mJ/cm^2 (Fenniche, et al. 2018). Increase by 50 mJ each session if no adverse effects occur; if burns or blisters appear then stop all treatment until completely healed and return to the next lowest safe setting. Use sunscreen on treated areas after each session. Optionally pure khellin 1–2% can be applied topically if available. Note that sun exposure in far northern climes, especially in the winter, may not be sufficiently intense for real benefit (trials conducted closer to the equator report better results than those further from the equator for the most part).
Decoction: 1 level tsp of fruit, simmer covered for 10 min in 250 ml of water, strain, this makes one "cup" (not 8 oz, just one dose), drink 1 cup per dose (up to q2h for severe acute problems like ureteral colic, up to tid for less severe, ongoing spasms like in BPH). This is not very readily available in North America for this application.
Capsules:
Extract standardized to 12% khellin, 300–1000 mg tid as a spasmolytic or 300–1000 mg once daily as a photosensitizer, followed 45 min later by 15 min sun exposure or UVA/B therapy (dose form not known to be available in North America),
Khellin, pure: 50 mg tid as a spasmolytic, 30–100 mg once daily as a photosensitizer, followed 45 min later by 15 min sun exposure or UVA/B therapy (dose form not known to be available in North America)
Dose:
Acute, adult: 1–3 ml up to q2h, adjusted for body size and sensitivities
Chronic, adult: 1–3 ml qd to tid
Child: as adult but adjusted for body size
For BPH or other conditions causing spasms at night, the last dose should be taken at bedtime.
For use for autoimmune skin diseases, follow at least one daily dose 45 min later with 15 min sunshine or UVA/B therapy.
Topical use: apply tincture liberally to vitiligo or psoriasis patches, them cover surrounding areas with sunscreen. Apply UVA or UVB light 45 min after application twice a week or go out into direct sunshine for 15 min. UVB dose: 308 nm Excilite laser 240 mJ/cm^2 (Fenniche, et al. 2018). Increase by 50 mJ each session if no adverse effects occur; if burns or blisters appear then stop all treatment until completely healed and return to the next lowest safe setting. Use sunscreen on treated areas after each session. Optionally pure khellin 1–2% can be applied topically if available. Note that sun exposure in far northern climes, especially in the winter, may not be sufficiently intense for real benefit (trials conducted closer to the equator report better results than those further from the equator for the most part).
Decoction: 1 level tsp of fruit, simmer covered for 10 min in 250 ml of water, strain, this makes one "cup" (not 8 oz, just one dose), drink 1 cup per dose (up to q2h for severe acute problems like ureteral colic, up to tid for less severe, ongoing spasms like in BPH). This is not very readily available in North America for this application.
Capsules:
Extract standardized to 12% khellin, 300–1000 mg tid as a spasmolytic or 300–1000 mg once daily as a photosensitizer, followed 45 min later by 15 min sun exposure or UVA/B therapy (dose form not known to be available in North America),
Khellin, pure: 50 mg tid as a spasmolytic, 30–100 mg once daily as a photosensitizer, followed 45 min later by 15 min sun exposure or UVA/B therapy (dose form not known to be available in North America)
Other Names
Latin Synonyms:
Current correct Latin binomial: Visnaga daucoides Gaertn (this name has not yet garnered widespread use; at least two phylogenetic analyses have concluded this plant is not part of genus Ammi [Jiménez-Mejías and Vargas 2015; Downie, et al. 2010])
Ammi visnaga (L) Lam
Ammi dilatatum St-Lag
Apium visnaga (L) Crantz
Carum visnaga (L) Koso-Pol
Daucus gingidium L ex DC
Daucus laevis Salisb
Daucus visnaga L
Selinum visnaga Krause
Sium visnaga (L) Stokes
Visnaga vera Raf
Ammi < Greek ammos, "sand" (referring to its preferred dry habitat, most likely). Visnaga is a corruption of Latin bis acutum, "doubly pointed."
English Common Names: khella, toothpick ammi, Spanish toothpick, bisnaga, visnaga, false Queen Anne's lace, bishop's weed (also and more often used for A. majus), false bishop's weed, bull wart, greater ammi, toothpick weed
The dried stems of this plant are indeed traditionally used as toothpicks around the Mediterranean.
Arabic Common Names: خلة بلدية, خلة, جزر بري, الخلة البرية
Berber Common Name: tabellaout
Catalan Common Names: bisnaga
Czech Common Names: pakmín visnaga, morač visnaga, morač zákrovnatý, pakmín pravý
Danish Common Names: tandstikkerurt, ammi, khella, sydlig kongekommen
Dutch Common Name: fijn akkerscherm
Esperanto Common Name: amio dikradia
Finnish Common Name: sirosudenporkkana
French Common Names: herbe au cure-dents, visnaga daucoides , ammi cure, ammi visnage, visnage, visnague
German Common Names: Bischofskraut, Bischofkraut, Zahnstocher-Ammei, Visnagafruchte, Khella, Khellakraut, Zahnstocher-knorpelmöhre, Zahnstocherkraut
Greek (Modern) Common Names: Άμμι το γλυφίδιον, Καραγάνι, Χαλαβάνα
Hebrew Common Names: אמיתה קיצית
Hungarian Common Name: fogpiszkálófű
Italian Common Names: visnaga, visnaga, busnaga, visnaga comune, visnage
Mandarin Chinese Common Name: 阿米芹, 齿阿米
Norwegian Common Names: tannstikke, tannsticke
Polish Common Names: aminek egipski, aminek zębodłubka, kela egipska
Portuguese Common Names: Âmio-bisnaga, bisnaga-das-searas, paliteira
Russian Common Names: á́мми зубна́я , aмми зубная, Висна́га
Spanish Common Names: visnaga, bisnaga, biznaga
Swedish Common Name: tandpetarsilja
Turkish Common Names: dişhilali, dişotu, hiltan, kürdanotu, köşni
Welsh Common Name: esgoblys praff
Current correct Latin binomial: Visnaga daucoides Gaertn (this name has not yet garnered widespread use; at least two phylogenetic analyses have concluded this plant is not part of genus Ammi [Jiménez-Mejías and Vargas 2015; Downie, et al. 2010])
Ammi visnaga (L) Lam
Ammi dilatatum St-Lag
Apium visnaga (L) Crantz
Carum visnaga (L) Koso-Pol
Daucus gingidium L ex DC
Daucus laevis Salisb
Daucus visnaga L
Selinum visnaga Krause
Sium visnaga (L) Stokes
Visnaga vera Raf
Ammi < Greek ammos, "sand" (referring to its preferred dry habitat, most likely). Visnaga is a corruption of Latin bis acutum, "doubly pointed."
English Common Names: khella, toothpick ammi, Spanish toothpick, bisnaga, visnaga, false Queen Anne's lace, bishop's weed (also and more often used for A. majus), false bishop's weed, bull wart, greater ammi, toothpick weed
The dried stems of this plant are indeed traditionally used as toothpicks around the Mediterranean.
Arabic Common Names: خلة بلدية, خلة, جزر بري, الخلة البرية
Berber Common Name: tabellaout
Catalan Common Names: bisnaga
Czech Common Names: pakmín visnaga, morač visnaga, morač zákrovnatý, pakmín pravý
Danish Common Names: tandstikkerurt, ammi, khella, sydlig kongekommen
Dutch Common Name: fijn akkerscherm
Esperanto Common Name: amio dikradia
Finnish Common Name: sirosudenporkkana
French Common Names: herbe au cure-dents, visnaga daucoides , ammi cure, ammi visnage, visnage, visnague
German Common Names: Bischofskraut, Bischofkraut, Zahnstocher-Ammei, Visnagafruchte, Khella, Khellakraut, Zahnstocher-knorpelmöhre, Zahnstocherkraut
Greek (Modern) Common Names: Άμμι το γλυφίδιον, Καραγάνι, Χαλαβάνα
Hebrew Common Names: אמיתה קיצית
Hungarian Common Name: fogpiszkálófű
Italian Common Names: visnaga, visnaga, busnaga, visnaga comune, visnage
Mandarin Chinese Common Name: 阿米芹, 齿阿米
Norwegian Common Names: tannstikke, tannsticke
Polish Common Names: aminek egipski, aminek zębodłubka, kela egipska
Portuguese Common Names: Âmio-bisnaga, bisnaga-das-searas, paliteira
Russian Common Names: á́мми зубна́я , aмми зубная, Висна́га
Spanish Common Names: visnaga, bisnaga, biznaga
Swedish Common Name: tandpetarsilja
Turkish Common Names: dişhilali, dişotu, hiltan, kürdanotu, köşni
Welsh Common Name: esgoblys praff
Interchangeability of Species
Khella is decidedly NOT interchangeable with its cousin A. majus (bishop's weed), which is far more phototoxic. The next closet herb the author has found in terms of potency and safety as a spasmolytic is Piscidia piscipula (Jamaica dogwood) bark, but this is far less sustainable than easily cultivable khella.
Advanced Clinical Information
Additional Actions:
In a clinical trial, 14 men with normal serum lipids were given khellin 50 mg po qid for 4 weeks after taking placebo for 2 weeks (Harvengt and Desager 1983). HDL cholesterol levels rose significantly during khellin treatment compared to the placebo period, though four subjects dropped out of the trial due to vomiting. Two subjects had elevated serum transaminases during khellin therapy. No other serum lipid levels changed during treatment. Studies in monkeys found khellin lowered LDL, HDL, and total cholesterol levels (Stevens, et al. 1985).
Additional Indications:
Pharmacokinetics:
Khellin is better absorbed from whole plant extracts than in isolation (Eder and Mehnert 2000).
- HDL cholesterol elevator (Harvengt and Desager 1983)
- Hypochlorhydric (Jan 2014)
- Acaricidal (Pavel 2015)
- Mosquito larvicidal (Pavel 2008)
- Antineoplastic and hepatoprotective against liver cancer (Arafah, et al. 2021)
In a clinical trial, 14 men with normal serum lipids were given khellin 50 mg po qid for 4 weeks after taking placebo for 2 weeks (Harvengt and Desager 1983). HDL cholesterol levels rose significantly during khellin treatment compared to the placebo period, though four subjects dropped out of the trial due to vomiting. Two subjects had elevated serum transaminases during khellin therapy. No other serum lipid levels changed during treatment. Studies in monkeys found khellin lowered LDL, HDL, and total cholesterol levels (Stevens, et al. 1985).
Additional Indications:
- Atherosclerosis, coronary artery disease (Di Giuseppe 1951; Best and Coe 1950)
- Dyslipidemia, with low HDL (Harvengt and Desager 1983)
Pharmacokinetics:
Khellin is better absorbed from whole plant extracts than in isolation (Eder and Mehnert 2000).
Classic Formulas
Spasmodic BPH Formula by Eric Yarnell, ND, RH(AHG)
- Ammi visnaga (khella) fruit tincture, 20% (lead spasmolytic)
- Paeonia lactiflora (white peony) root without bark tincture, 20% (supportive spasmolytic, hormone modulator)
- Chamaenerion angustifolium (fireweed) aerial parts tincture 30% (supportive growth inhibitor)
- Urtica dioica (stinging nettle) root tincture 20% (supportive anti-SHBG growth inhibitor)
- Fouquieria splendens (ocotillo) bark tincture 10% (pelvic lymphagogue)
Monograph from Materia Medica Vegetabilis (Steinmetz 1954)
SEMEN AMMI VISNAGA, Umbelliferae, Ammi visnaga
Ammi visnaga seeds. The tincture or its active principle khellin, obtained by extracting the fruits (wrongly called "seeds") in alcohol, is known for its antispasmodic action. It is employed principally to lessen the spasm of the ureter, of the liverduct, of angina of the chest, of bronchial asthma and of whooping cough. It is a powerful vasodilator, particularly forthe cononary arteries of the heart, which does not raise the blood pressure or increase the oxygen requirements of the lungs. Owing to these properties it is a valuable remedy in angina pectoris. It is also good against sclerosis of the coronary arteries, Besides khellin, khellol and visnagin (visammin) are extracted from the fruits, It is mainly khellin, which possesses therapeutical value. Its effect is less immediate than of adrenaline or ephedrine, but more lasting than either, The drug is more effective than nitroglycerine, often administered in angina pectoris, the action of which is also of a much shorter duration. The number of coughs, their intensity and their duration are rapidly and powerfully reduced, The general condition of the patient soon improves, particularly as regards sleep and appetite. This medicine is not dangerous and causes no after effects, not even to small children, On account of its bitter taste, the medicine should be given in orange syrup. The usual dose is 5–7 milligrammes per kiligramme bodyweight, devided in 3 to 4 gifts daily and given during the period of paroxysm.
Ammi visnaga seeds. The tincture or its active principle khellin, obtained by extracting the fruits (wrongly called "seeds") in alcohol, is known for its antispasmodic action. It is employed principally to lessen the spasm of the ureter, of the liverduct, of angina of the chest, of bronchial asthma and of whooping cough. It is a powerful vasodilator, particularly forthe cononary arteries of the heart, which does not raise the blood pressure or increase the oxygen requirements of the lungs. Owing to these properties it is a valuable remedy in angina pectoris. It is also good against sclerosis of the coronary arteries, Besides khellin, khellol and visnagin (visammin) are extracted from the fruits, It is mainly khellin, which possesses therapeutical value. Its effect is less immediate than of adrenaline or ephedrine, but more lasting than either, The drug is more effective than nitroglycerine, often administered in angina pectoris, the action of which is also of a much shorter duration. The number of coughs, their intensity and their duration are rapidly and powerfully reduced, The general condition of the patient soon improves, particularly as regards sleep and appetite. This medicine is not dangerous and causes no after effects, not even to small children, On account of its bitter taste, the medicine should be given in orange syrup. The usual dose is 5–7 milligrammes per kiligramme bodyweight, devided in 3 to 4 gifts daily and given during the period of paroxysm.
Botanical Information
Botanical Description: Khella is an annual herb that grows up to 100 cm tall with highly branched, erect stems. The leaves are alternate, pinnate (branching 1–2 times in lower leaves and 2–4 times in the upper leaves), and highly dissected (thead-like). Its tiny white, bisexual flowers are borne in umbels. It typically flowers from April–August. It has tiny fruits. Unlike its toxic cousin Conium maculatum (poison hemlock), it does not have a spotted stem and all plant parts smell pleasant.
Native Range: It is native all around the Mediterranean basin.
Native Range: It is native all around the Mediterranean basin.
Harvesting, Cultivation, and Ecology
References
Abdel-Fattah A, Aboul-Enein MN, Wassel GM, El-Menshawi BS (1982) "An approach to the treatment of vitiligo by khellin" Dermatologica 165(2):136–40.
Abdel-Fattah A, Aboul-Enein MN, Wassel G, El-Menshawi B (1983) "Preliminary report on the therapeutic effect of khellin in psoriasis" Dermatologica 167(2):109–10.
Al-Shoubaki R, Ahmed AKL, Sheikh I, Shaheen F (2020) "Khella induced nephropathy: A case report and review of literature" Urol Nephrol Open Access J 8(3):62–4.
Alouani I, Fihmi N, Zizi N, Dikhaye S (2018) "Phytophotodermatitis following the use of Ammi majus Linn (bishop’s weed) for vitiligo" Our Dermatol Online 9(1):93–94.
Anrep GV, Barsoum GS, Kenawy MR, Misrahy G (1946) "Ammi visnaga in the treatment of the anginal syndrome" Br Heart J 8(4):171–7.
Anrep GV, Kenawy MR, Barsoum GS (1949) "Coronary vasodilator action of khellin" Am Heart J 37(4):531–42.
Arafah MW, Almutairia B, Al-Zharani M, et al. (2021) "The protective effect of Ammi visnaga extract against human hepatic cancer" J King Saud Univ Sci 33(6):101540.
Armbrust CA Jr and Levine SA (1950) "The treatment of angina pectoris with a preparation of khellin (Ammi visnaga)" Am J Med Sci 220(2):127–32.
Badr JM, Hadad GM, Nahriry K, Hassanean HA (2015) "Validated HPLC method for simultaneous estimation of khellol glucoside, khellin and visnagin in Ammi visnaga L fruits and pharmaceutical preparations" Nat Prod Res 29(7):593–601.
Best MM, Coe WS (1950) "Effect of khellin on coronary artery insufficiency as evaluated by electrocardiographic tests" Circulation 2(3):344–50.
Bhagavathula AS, Al-Khatib AJM, Elnour AA, et al. (2015) "Ammi visnaga in treatment of urolithiasis and hypertriglyceridemia" Pharmacognosy Res 7(4):397–400.
Bishr MM, El-Degwy MA, Amin MA, Salama OM (2016) "HPLC simultaneous determination of khellin and visnagin in Ammi visnaga L fruits" IOSR J Pharm Biol Sci 11(6):110–5.
Carlie G, Ntusi NB, Hulley PA, Kidson SH (2003) "KUVA (khellin plus ultraviolet A) stimulates proliferation and melanogenesis in normal human melanocytes and melanoma cells in vitro" Br J Dermatol 149(4):707–17.
Charafi S, Kzaiber F, Hafid A, et al. (2012) "Study of Ammi visnaga Lam on oxalocalcic crystallization" Glob J Tradit Med Syst 1(1):7–12.
Chysanthis K (1950) "Infusion of khella seeds in the treatment of bronchial asthma" Cyprus Med J 3(4):333–335 [in Greek].
de Leeuw J, van der BN, Maierhofer G, Neugebauer WD (2003) "A case study to evaluate the treatment of vitiligo with khellin encapsulated in L-phenylalanin stabilized phosphatidylcholine liposomes in combination with ultraviolet light therapy" Eur J Dermatol 13(5):474–7.
Dewar H, Grimson T (1950) "Khellin in the treatment of angina of effort" Br Heart J 12:54–60.
Di Giuseppe F (1951) "Experience with khellin therapy in coronary disease" Minerva Med 42(54–55):219–23 [in Italian].
Downie SR, Spalik K, Katz-Downie DS, Reduron JP (2010) "Major clades within Apiaceae subfamily Apioideae as inferred by phylogenetic analysis of nrDNA ITS sequences" Plant Diversity and Evolution 128(1–2):111–36.
Duarte J, Vallejo I, Vizcaino FP, et al. (1997) "Effects of visnadine on rat isolated vascular smooth muscles" Planta Med 63(3):233–6.
Eder M, Mehnert W (2000) " Plant excipients—valuable pharmaceutical aids or superfluous ballast?" Pharm Unserer Zeit 29(6):377–84 [in German].
el-Domiaty MM (1992) "Improved high-performance liquid chromatographic determination of khellin and visnagin in Ammi visnaga fruits and pharmaceutical formulations" J Pharm Sci 81(5):475–8.
Erbring H, Uebel H, Vogel G (1967) "Chemistry, pharmacology, and toxicology of visnadine" Arzneimittelforschung 17:283–7 [in German].
Farrand RL, Horvath SM (1959) "Effects of khellin on coronary blood flow and related metabolic functions" Am J Physiol 196(2):391–3.
Fenniche S, Zaouak A, Ben Tanfous A, et al. (2018) "Successful treatment of refractory vitiligo with a combination of khellin and 308-nm excimer lamp: An open-label, 1-year prospective study" Dermatol There (Heidelb) 8(1):127–35.
Franchi GG, Bovalini L, Martelli P, et al. (1985) "High performance liquid chromatography analysis of the furanochromones khellin and visnagin in various organs of Ammi visnaga (L) Lam at different developmental stages" J Ethnopharmacol 14(2–3):203–12.
Harvengt C, Desager JP (1983) "HDL-cholesterol increase in normolipaemic subjects on khellin: A pilot study" Int J Clin Pharmacol Res 3(5):363–6.
Hauviller OA, Asrilant M (1955) "Clinical testing of the bronchodilatatory action of khellin in pediatrics" Prensa Med Argent 42(15):1037–42 [in Spanish].
Hultgren HN, Robertson HS, Stevens LE (1952) "Clinical and experimental study of use of khellin in treatment of angina pectoris" JAMA 148(6):465–9.
Jan M (2014) "Effects of Ammi visnaga (bisnaga) extract on the volume and acidity of stimulated gastric secretion in fasting rabbits" J Coll Physicians Surg Pak 24(1):39–42.
Jiménez-Mejías P, Vargas P (2015) "Taxonomy of the tribe Apieae (Apiaceae) revisited as revealed by molecular phylogenies and morphological characters" Phytotaxa 212(1):57–79.
Kachkoul R, Houssaini S, Miyah Y, et al. (2018) "The study of the inhibitory effect of calcium oxalate monohydrate's crystallization by two medicinal and aromatic plants: Ammi visnaga and Punica granatum" Progrès en Urologie 28(3):156–65.
Kamal A, Khan W, Ahmad S, et al. (2015) "Development and validation of high-performance liquid chromatography and high-performance thin-layer chromatography methods for the quantification of khellin in Ammi visnaga seed" J Pharm Bioallied Sci 7(4):308–13.
Karawya MS, el-Kiey MA, Sina A, Nour G (1970) "Simultaneous TLC separation of khellin and visnagin and their assay in Ammi visnaga fruits, extracts, and formulations" J Pharm Sci 59(7):1025–7.
Kennedy MCS, Stock JPP (1952) "The bronchodilator action of khellin" Thorax 7(1):43–65.
Kenawy MR, Barsoum GS (1945) "Ammi visnaga in the treatment of the anginal syndrome" Gazette of the Faculty of Medicine, Cairo, Egypt 13:33.
Khalil N, Bishr M, Desouky S, Salama O (2020) "Ammi visnaga L, a potential medicinal plant: A review" Molecules 25(2):E301.
Khan ZA, Assiri AM, Al-Afghani HM, Maghrabi TM (2001) "Inhibition of oxalate nephrolithiasis with Ammi visnaga (AI-Khillah)" Int Urol Nephrol 33(4):605–8.
Meyer U (2002) "From khellin to sodium cromoglycate – A tribute to the work of Dr. R. E. C. Altounyan (1922–1987)" Pharmazie 57(1):62–9.
Morliere P, Honigsmann H, Averbeck D, et al. (1988) "Phototherapeutic, photobiologic, and photosensitizing properties of khellin" J Invest Dermatol 90(5):720–4.
Modli'nski L (1977) "Experiences with Nephrolith in the treatment of kidney stones" Z Urol Nephrol 70:429–35 [in German].
Nalefski LA, Rudy WB, Gilbert NC (1952) "The use of crystalline visammin in the treatment of angina pectoris" Circulation 5(6):851–7.
Orecchia G, Sangalli ME, Gazzaniga A, Giordano F (1998) "Topical photochemotherapy of vitiligo with a new khellin formulation: Preliminary clinical results" J Dermatol 9:65–69.
Ortonne JP (1998) "Topical KUVA (khellin-UVA therapy). A future in the treatment of vitiligo?" J Dermatol Treat 9:63–64.
Osher HL, Katz KH, Wagner DJ (1951) "Khellin in the treatment of angina pectoris" N Engl J Med 244(9):315–21.
Ossenkoppele PM, van der Sluis WG, van Vloten WA (1991) "Phototoxic dermatitis following the use of Ammi majus fruit for vitiligo" Ned Tijdschr Geneeskd 135(11):478–80 [in Dutch].
Pavela R (2008) "Larvicidal effects of various Euro-Asiatic plants against Culex quinquefasciatus Say larvae (Diptera: Culicidae)" Parasitol Res 102(3):555–9.
Pavela R (2015) "Acaricidal properties of extracts and major furanochromenes from the seeds of Ammi visnaga Linn against Tetranychus urticae " Indust Crops Prod 67:108–13.
Rauwald HW, Brehm O, Odenthal KP (1994) "The involvement of a Ca2+-channel blocking mode of action in the pharmacology of Ammi visnaga fruits" Planta Med 60(2):101–5.
Shlosberg A, Egyed MN, Eilat A (1974) "The comparative photosensitizing properties of Ammi majus and Ammi visnaga in goslings" Avian Dis 18(4):544–50.
Schmidt L (1958) "Dilating effect of khellin on coronary vessels" Klin Wochenschr 36(3):127–9 [in German].
Steinmetz EF (1954) Materia Medica Vegetabilis volume 1 (Amsterdam: Self-published).
Sternieri E, Cortesi N, Montanari C (1961) "Coronary dilator action of an active principle extract of Ammi visnaga" Arch Ital Sci Farmacol 11:97–106 [in Italian].
Stevens TJ, Jones BW, Vidmar TJ, et al. (1985) "Hypocholesterolemic effect of khellin and khelloside in female cynomolgus monkeys" Arzneimittelforschung 35(8):1257–60.
Ubeda A, Villar A (1989) "Relaxant actions of khellin on vascular smooth muscle" J Pharm Pharmacol 41(4):236–41.
Uhlenbroock K, Schweer M (1960) "On the question of the coronary dilating effect of khellin" Arzneimittelforschung 10:2937 [in German].
Vedaldi D, Caffieri S, Dall'Acqua F, et al. (1988) "Khellin, a naturally occurring furochromone, used for the photochemotherapy of skin diseases: Mechanism of action" Farmaco Sci 43(4):333–46.
Velazquez VL, Aparicio Dominguez L, Lucea A (1961) "Experimental study of the coronary vasodilative action of visnagan" Arch Inst Farmacol Exp (Madr) 13:217–34 [in Spanish].
Weiss RF (2001) Herbal Medicine Classic Ed (New York: Thieme Medical Publications).
Yarnell E (2018) Naturopathic Approach to Prostate Conditions 2nd ed (Wenatchee, WA: Wild Brilliance Press).
Abdel-Fattah A, Aboul-Enein MN, Wassel G, El-Menshawi B (1983) "Preliminary report on the therapeutic effect of khellin in psoriasis" Dermatologica 167(2):109–10.
Al-Shoubaki R, Ahmed AKL, Sheikh I, Shaheen F (2020) "Khella induced nephropathy: A case report and review of literature" Urol Nephrol Open Access J 8(3):62–4.
Alouani I, Fihmi N, Zizi N, Dikhaye S (2018) "Phytophotodermatitis following the use of Ammi majus Linn (bishop’s weed) for vitiligo" Our Dermatol Online 9(1):93–94.
Anrep GV, Barsoum GS, Kenawy MR, Misrahy G (1946) "Ammi visnaga in the treatment of the anginal syndrome" Br Heart J 8(4):171–7.
Anrep GV, Kenawy MR, Barsoum GS (1949) "Coronary vasodilator action of khellin" Am Heart J 37(4):531–42.
Arafah MW, Almutairia B, Al-Zharani M, et al. (2021) "The protective effect of Ammi visnaga extract against human hepatic cancer" J King Saud Univ Sci 33(6):101540.
Armbrust CA Jr and Levine SA (1950) "The treatment of angina pectoris with a preparation of khellin (Ammi visnaga)" Am J Med Sci 220(2):127–32.
Badr JM, Hadad GM, Nahriry K, Hassanean HA (2015) "Validated HPLC method for simultaneous estimation of khellol glucoside, khellin and visnagin in Ammi visnaga L fruits and pharmaceutical preparations" Nat Prod Res 29(7):593–601.
Best MM, Coe WS (1950) "Effect of khellin on coronary artery insufficiency as evaluated by electrocardiographic tests" Circulation 2(3):344–50.
Bhagavathula AS, Al-Khatib AJM, Elnour AA, et al. (2015) "Ammi visnaga in treatment of urolithiasis and hypertriglyceridemia" Pharmacognosy Res 7(4):397–400.
Bishr MM, El-Degwy MA, Amin MA, Salama OM (2016) "HPLC simultaneous determination of khellin and visnagin in Ammi visnaga L fruits" IOSR J Pharm Biol Sci 11(6):110–5.
Carlie G, Ntusi NB, Hulley PA, Kidson SH (2003) "KUVA (khellin plus ultraviolet A) stimulates proliferation and melanogenesis in normal human melanocytes and melanoma cells in vitro" Br J Dermatol 149(4):707–17.
Charafi S, Kzaiber F, Hafid A, et al. (2012) "Study of Ammi visnaga Lam on oxalocalcic crystallization" Glob J Tradit Med Syst 1(1):7–12.
Chysanthis K (1950) "Infusion of khella seeds in the treatment of bronchial asthma" Cyprus Med J 3(4):333–335 [in Greek].
de Leeuw J, van der BN, Maierhofer G, Neugebauer WD (2003) "A case study to evaluate the treatment of vitiligo with khellin encapsulated in L-phenylalanin stabilized phosphatidylcholine liposomes in combination with ultraviolet light therapy" Eur J Dermatol 13(5):474–7.
Dewar H, Grimson T (1950) "Khellin in the treatment of angina of effort" Br Heart J 12:54–60.
Di Giuseppe F (1951) "Experience with khellin therapy in coronary disease" Minerva Med 42(54–55):219–23 [in Italian].
Downie SR, Spalik K, Katz-Downie DS, Reduron JP (2010) "Major clades within Apiaceae subfamily Apioideae as inferred by phylogenetic analysis of nrDNA ITS sequences" Plant Diversity and Evolution 128(1–2):111–36.
Duarte J, Vallejo I, Vizcaino FP, et al. (1997) "Effects of visnadine on rat isolated vascular smooth muscles" Planta Med 63(3):233–6.
Eder M, Mehnert W (2000) " Plant excipients—valuable pharmaceutical aids or superfluous ballast?" Pharm Unserer Zeit 29(6):377–84 [in German].
el-Domiaty MM (1992) "Improved high-performance liquid chromatographic determination of khellin and visnagin in Ammi visnaga fruits and pharmaceutical formulations" J Pharm Sci 81(5):475–8.
Erbring H, Uebel H, Vogel G (1967) "Chemistry, pharmacology, and toxicology of visnadine" Arzneimittelforschung 17:283–7 [in German].
Farrand RL, Horvath SM (1959) "Effects of khellin on coronary blood flow and related metabolic functions" Am J Physiol 196(2):391–3.
Fenniche S, Zaouak A, Ben Tanfous A, et al. (2018) "Successful treatment of refractory vitiligo with a combination of khellin and 308-nm excimer lamp: An open-label, 1-year prospective study" Dermatol There (Heidelb) 8(1):127–35.
Franchi GG, Bovalini L, Martelli P, et al. (1985) "High performance liquid chromatography analysis of the furanochromones khellin and visnagin in various organs of Ammi visnaga (L) Lam at different developmental stages" J Ethnopharmacol 14(2–3):203–12.
Harvengt C, Desager JP (1983) "HDL-cholesterol increase in normolipaemic subjects on khellin: A pilot study" Int J Clin Pharmacol Res 3(5):363–6.
Hauviller OA, Asrilant M (1955) "Clinical testing of the bronchodilatatory action of khellin in pediatrics" Prensa Med Argent 42(15):1037–42 [in Spanish].
Hultgren HN, Robertson HS, Stevens LE (1952) "Clinical and experimental study of use of khellin in treatment of angina pectoris" JAMA 148(6):465–9.
Jan M (2014) "Effects of Ammi visnaga (bisnaga) extract on the volume and acidity of stimulated gastric secretion in fasting rabbits" J Coll Physicians Surg Pak 24(1):39–42.
Jiménez-Mejías P, Vargas P (2015) "Taxonomy of the tribe Apieae (Apiaceae) revisited as revealed by molecular phylogenies and morphological characters" Phytotaxa 212(1):57–79.
Kachkoul R, Houssaini S, Miyah Y, et al. (2018) "The study of the inhibitory effect of calcium oxalate monohydrate's crystallization by two medicinal and aromatic plants: Ammi visnaga and Punica granatum" Progrès en Urologie 28(3):156–65.
Kamal A, Khan W, Ahmad S, et al. (2015) "Development and validation of high-performance liquid chromatography and high-performance thin-layer chromatography methods for the quantification of khellin in Ammi visnaga seed" J Pharm Bioallied Sci 7(4):308–13.
Karawya MS, el-Kiey MA, Sina A, Nour G (1970) "Simultaneous TLC separation of khellin and visnagin and their assay in Ammi visnaga fruits, extracts, and formulations" J Pharm Sci 59(7):1025–7.
Kennedy MCS, Stock JPP (1952) "The bronchodilator action of khellin" Thorax 7(1):43–65.
Kenawy MR, Barsoum GS (1945) "Ammi visnaga in the treatment of the anginal syndrome" Gazette of the Faculty of Medicine, Cairo, Egypt 13:33.
Khalil N, Bishr M, Desouky S, Salama O (2020) "Ammi visnaga L, a potential medicinal plant: A review" Molecules 25(2):E301.
Khan ZA, Assiri AM, Al-Afghani HM, Maghrabi TM (2001) "Inhibition of oxalate nephrolithiasis with Ammi visnaga (AI-Khillah)" Int Urol Nephrol 33(4):605–8.
Meyer U (2002) "From khellin to sodium cromoglycate – A tribute to the work of Dr. R. E. C. Altounyan (1922–1987)" Pharmazie 57(1):62–9.
Morliere P, Honigsmann H, Averbeck D, et al. (1988) "Phototherapeutic, photobiologic, and photosensitizing properties of khellin" J Invest Dermatol 90(5):720–4.
Modli'nski L (1977) "Experiences with Nephrolith in the treatment of kidney stones" Z Urol Nephrol 70:429–35 [in German].
Nalefski LA, Rudy WB, Gilbert NC (1952) "The use of crystalline visammin in the treatment of angina pectoris" Circulation 5(6):851–7.
Orecchia G, Sangalli ME, Gazzaniga A, Giordano F (1998) "Topical photochemotherapy of vitiligo with a new khellin formulation: Preliminary clinical results" J Dermatol 9:65–69.
Ortonne JP (1998) "Topical KUVA (khellin-UVA therapy). A future in the treatment of vitiligo?" J Dermatol Treat 9:63–64.
Osher HL, Katz KH, Wagner DJ (1951) "Khellin in the treatment of angina pectoris" N Engl J Med 244(9):315–21.
Ossenkoppele PM, van der Sluis WG, van Vloten WA (1991) "Phototoxic dermatitis following the use of Ammi majus fruit for vitiligo" Ned Tijdschr Geneeskd 135(11):478–80 [in Dutch].
Pavela R (2008) "Larvicidal effects of various Euro-Asiatic plants against Culex quinquefasciatus Say larvae (Diptera: Culicidae)" Parasitol Res 102(3):555–9.
Pavela R (2015) "Acaricidal properties of extracts and major furanochromenes from the seeds of Ammi visnaga Linn against Tetranychus urticae " Indust Crops Prod 67:108–13.
Rauwald HW, Brehm O, Odenthal KP (1994) "The involvement of a Ca2+-channel blocking mode of action in the pharmacology of Ammi visnaga fruits" Planta Med 60(2):101–5.
Shlosberg A, Egyed MN, Eilat A (1974) "The comparative photosensitizing properties of Ammi majus and Ammi visnaga in goslings" Avian Dis 18(4):544–50.
Schmidt L (1958) "Dilating effect of khellin on coronary vessels" Klin Wochenschr 36(3):127–9 [in German].
Steinmetz EF (1954) Materia Medica Vegetabilis volume 1 (Amsterdam: Self-published).
Sternieri E, Cortesi N, Montanari C (1961) "Coronary dilator action of an active principle extract of Ammi visnaga" Arch Ital Sci Farmacol 11:97–106 [in Italian].
Stevens TJ, Jones BW, Vidmar TJ, et al. (1985) "Hypocholesterolemic effect of khellin and khelloside in female cynomolgus monkeys" Arzneimittelforschung 35(8):1257–60.
Ubeda A, Villar A (1989) "Relaxant actions of khellin on vascular smooth muscle" J Pharm Pharmacol 41(4):236–41.
Uhlenbroock K, Schweer M (1960) "On the question of the coronary dilating effect of khellin" Arzneimittelforschung 10:2937 [in German].
Vedaldi D, Caffieri S, Dall'Acqua F, et al. (1988) "Khellin, a naturally occurring furochromone, used for the photochemotherapy of skin diseases: Mechanism of action" Farmaco Sci 43(4):333–46.
Velazquez VL, Aparicio Dominguez L, Lucea A (1961) "Experimental study of the coronary vasodilative action of visnagan" Arch Inst Farmacol Exp (Madr) 13:217–34 [in Spanish].
Weiss RF (2001) Herbal Medicine Classic Ed (New York: Thieme Medical Publications).
Yarnell E (2018) Naturopathic Approach to Prostate Conditions 2nd ed (Wenatchee, WA: Wild Brilliance Press).