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Microsomes prepared from cultured Ammi majus cells that had been challenged for 14 h with an elicitor derived from the cell walls of Phytophthora megasperma f.sp. glycinea (Pmg) converted psoralen to bergaptol (5-hydroxypsoralen) in the presence of NADPH and oxygen. The enzymatic activity was characterized as an inducible cytochrome-P-450-dependent monooxygenase associated with the endoplasmic reticulum. All of the steps involved in bergapten (5-methoxypsoralen) biosynthesis in Ammi majus have now been demonstrated in vitro. The results suggest that bergaptol and not hydroxymarmesin in the precursor of bergapten.

Many naturally occurring plant furocoumarins (psoralens) show marked skin photosensitizing activity (1). The ancient Hindus, Turks, Egyptians, and other Orientals had exploited this property in popular medicine since ancient time (2,3). In fact, the use of Psoralea corylifolia for the treatment of vitiligo is mentioned in the Indian sacred book “Atharva Veda” and in the old Buddhist Bower manuscript (2,3). Furthermore, it is known that a green plant growing in the Nile valley, Ammi majus, has been used for centuries for the cure of the same disease (2,3).

(acetoxy)-3-hydroxy-3-methylbutoxy]psoralen, have apparently not been previously isolated from any plant source. Six other synthetic psoralens were not observed in the seed extracts. Most of the major A. majus psoralens are potent photosensitizers, based on bioassays against chick skin, and the presence of these compounds in the seed and other parts of A. majus almost certainly accounts for the high photosensitizing activity of this plant toward cattle and sheep.

Summary The plant Ammi majus (L.) was fed to 2 groups of young geese in an attempt to reproduce a field condition resembling photo‐sensitization. The group exposed to sunlight developed skin lesions on the footweb and beak, whereas the group housed indoors appeared normal, together with the control group, which was not fed the plant but was exposed to sunlight. Blood was taken 29 d after commencement of the feeding trial, and rises in serum enzyme levels of lactic dehydrogenase, glutamic oxaloacetic transaminase and isocitric dehydrogenase were noted in the group fed A. majus and kept indoors. Three days before sacrificing the birds, after 49 d of feeding the plant, blood was again taken and lowered levels of serum albumin were seen in both groups fed A. majus. Post‐mortem macroscopic and histological examinations demonstrated severe liver damage in the birds fed A. majus and exposed to sunlight.

The acute and chronic symptoms seen in ducks following Ammi majus induced photosensitisation are described. The acute changes were inflammatory in nature whereas the chronic changes included severe deformities of the beak and footwebs, mydriasis and eccentric location of the pupil.

Suspension cultures of Ammi majus L. cells produce various linear furanocoumarins in response to treatment with elicitor preparations from either Alternaria carthami Chowdhury or Phytophthora megasperma f.sp. glycinea. Microsomes which were isolated from these cells 14 h after addition of the elicitor efficiently catalyzed the conversion of demethyl [3-14C]suberosin into labelled (+)marmesin in the presence of NADPH and oxygen. In contrast to the chemical cyclization of demethylsuberosin by m-chloroperoxybenzoic acid, the reaction catalyzed by the marmesin synthase proceeded rapidly and no intermediate demethylsuberosin epoxide could be recovered. Significant blue-light-reversible inhibition by carbon monoxide and inhibition by various chemicals known to inhibit reactions dependent on cytochrome P450 suggested that the marmesin synthase is a cytochrome-P450-dependent monooxygenase. Upon prolonged incubation, a subsequent major labelled product originated from (+)marmesin, which was identified as psoralen. The psoralen synthase was also characterized as a cytochrome-P450-dependent monooxygenase. Both the marmesin synthase and the psoralen synthase, as well as enzymes catalyzing the formation of demethylsuberosin and O-prenylumbelliferone from umbelliferone and dimethylallyl diphosphate, were associated with the endoplasmic reticulum in Ammi majus cells and their activities were concomitantly induced by elicitor treatment of the cells. We propose that in vivo these enzymes are active in the lumen of the endoplasmic reticulum from where the furanocoumarin phytoalexins are excreted into the cell culture fluid.

COSMETIC disfiguration and psychologic sequelae constitute a serious problem for the patient with vitiligo. Reported successful treatment of this condition with the psoralen derivatives has stimulated considerable interest among physicians, but the frequent occurrence of undesirable side effects from local and oral application has discouraged their use. Despite careful local application of the drug, vesiculation and edema of the involved areas often develop before pigmentation occurs, and oral ingestion also is frequently associated with nausea and other gastrointestinal disturbances. The present clinical study was undertaken in an attempt to find an effective but safe treatment for vitiligo with the psoralen derivatives without undesirable side-effects. Psoralen derivatives are crystalline principles extracted from the Ammi majus Linn. fruits, found so abundantly in the Nile Delta. Since the 13th century Egyptians have used a powder prepared from the fruit of this plant for treatment of vitiligo. The crude

Ammi majus, spec. nov. 1. Ammi foliis inferioribus pinnatis lanceolatis serratis, superioribus multifidis linearibus. Hort. ups.59. Ammi laciniis foliorum caulis lanceolatis. Hort. cliff. 89. Roy. lugdb. 96. Sauv. monsp. 232. Ammi majus. Bauh. pin. 159. Ammi vulgare. Dod. pempt. 415. Habitat in Europa australi. ���, Published as part of Linnaeus, Carolus, 1753, Species plantarum: exhibentes plantas rite cognitas, ad genera relatas, cum differentiis specificis, nominibus trivialibus, synonymis selectis, locis natalibus, secundum systema sexuale digestas, Stockholm :Laurentius Salvius on page 243, DOI: 10.5281/zenodo.3931989

Fahmy and Abushady1 have isolated from the fruits of Ammi majus L. a crystalline product to which they gave the name ‘ammoidin'. We wish to express our gratitude to them for supplying us with this material and for allowing us to determine its constitution. We have found that the substance does not contain active hydrogen or an acetyl group2, but it contains one methoxyl grouping. Analysis of ammoidin gave the formula C12H2O4, and after degradation we found that it possesses the constitution

It was known from the ancient folk-medicine practiced by the natives of Egypt that derivatives of the plant Ammi majus Linn could restore pigment in vitiliginous skin areas. In 1947 Fahmy and Abu-Shady 1 isolated the most active agents from extracts of this plant. They initiated clinical studies which confirmed the native lore by demonstrating that both internal administration and external application of the plant extractives, when combined with exposure to sunlight, did indeed bring about repigmentation in certain patches of vitiligo. 2 Further confirmation of these facts was soon forthcoming in Egyptian publications and in the European and American literature. 3 The most active pigmentstimulating ingredients of the plant were found to be in the group of natural furocoumarins, compounds long known to possess photosensitizing properties. Among these compounds are the oxypsoralens. A good deal of the recent work in the United States has been done with methoxsalen (Meloxine

Labelling experiments with 14C and 3H have shown that linear furanocoumarins of Ammi majus, Angelica archangelica, Heracleum lanatum (Umbelliferae), and Ruta graveolens (Rutaceae) are formed from umbelliferone via the dihydrofuranocoumarin, marmesin. The unsubstituted furanocoumarin psoralen is formed first, and hydroxylation and O-methylation then lead to methoxy-substituted derivatives, with other alkylated psoralens assumed to be formed analogously. No evidence was obtained for oxygenation of the coumarin nucleus before attachment of a side chain, since oxygenated umbelliferones were poorly utilized for furanocoumarin biosynthesis. A detailed biosynthetic route to linear furanocoumarins, consistent with known stereochemistry, is proposed.A separation of furanocoumarins by column partition chromatography on formamide-impregnated silica, and syntheses of [3-14C]umbelliferone, [2-14C]- and [3-14C]skimmin, [3-14C]daphnetin, [2-14C]-7-hydroxy-8-methoxycoumarin, and [2-14C]5-methoxy-7-hydroxycoumarin are described.

The production of coumarins and furanocoumarins (FCs) in higher plants is widely considered a model illustration of the adaptation of plants to their environment. In this report, we show that the multiplication of cytochrome P450 variants within the CYP71AZ subfamily has contributed to the diversification of these molecules. Multiple copies of genes encoding this enzyme family are found in Apiaceae, and their phylogenetic analysis suggests that they have different functions within these plants. CYP71AZ1 from Ammi majus and CYP71AZ3, 4, and 6 from Pastinaca sativa were functionally characterized. While CYP71AZ3 merely hydroxylated esculetin, the other enzymes accepted both simple coumarins and FCs. Superimposing in silico models of these enzymes led to the identification of different conformations of three regions in the enzyme active site. These sequences were subsequently utilized to mutate CYP71AZ4 to resemble CYP71AZ3. The swapping of these regions lead to significantly modified substrate specificity. Simultaneous mutations of all three regions shifted the specificity of CYP71AZ4 to that of CYP71AZ3, exclusively accepting esculetin. This approach may explain the evolution of this cytochrome P450 family regarding the appearance of FCs in parsnip and possibly in the Apiaceae.

Ammi majus L.1 (Umbelliferse) is an annual herbaceous plant which is widely spread in the Nile, delta region and closely resembles Ammi visnaga L. The fruits of Ammi majus are taken internally by the public to cure leukoderma.

Chronic lesions of the beak, footweb, and eye of geese photosensitized by the comsumption of Ammi majus (L.) are described, 7 weeks after the acute symptoms commenced. Sixty-four (48%) of the 133 birds in the flock showed various degrees of abnormality. All affected birds had stunting of the upper beak and cicatrization and thickening of the footweb. Eighty-nine percent of the affected birds showed ocular involvement, comprising chemosis, blepharoconjunctivitis, keratitis, symblepharon, ankyloblepharon, cicatricial ectropium, and mydriasis.

SUMMARY This study compared the ability of the closely related plants Ammi majus (L.) and Ammi visnaga (L.) Lam. to induce photosensitization, with goslings as the experimental model. Goslings fed stems, leaves, and flowers of A. visnaga failed to develop clinical symptoms of photosensitization. The same weight of seeds of the two plants fed to goslings caused photosensitization solely in the geese fed A. majus seeds. Only birds both fed A. majus seeds and exposed to sunlight were clinically affected. A brief botanical description of the two plants is given to aid in their identification.

Vitiligo, an acquired, idiopathic leucoderma, has long been a vexing therapeutic problem for the physician. Therapy for this affliction has included use of ultraviolet light, freezing with carbon dioxide snow, injections of gold thiosulfate, topical applications of bergamot oil, administration of pituitary melanocyte-stimulating hormone (MSH), and the systemic and tropical use of the psoralen compounds. We wish to present our experiences with the last-named substances. For many centuries, Egyptians have used the fruit of the Ammi majus Linn, plant in the treatment of vitiligo. A powder was prepared from this plant and ingested with simultaneous exposure of the affected skin to sunlight. While this treatment often produced improvement or a cure, its use not infrequently provoked numerous undesirable side-effects, including erythema and vesiculation of the skin, vomiting, diarrhea, nausea, headache, nephritis, hepatitis, coma, and exfoliative dermititis. In 1947, Fahmy and Abu-Shady isolated from the crude

Under ordinary circumstances long ultraviolet light (wavelengths longer than about 3,200 A.) is incapable of damaging the eye. Verhoeff and Bell 1 placed the upper limit of the keratitis spectrum in rabbits at 3,050 A., while Cogan and Kinsey 2 placed it between 3,060 A. and 3,260 A. The longer wavelengths are also incapable of causing certain reactions in the skin. The upper limit of the action spectrum for erythema in humans, for instance, is about 3,200 A. 3 Attention has recently been focused upon a photosensitizing agent, methoxsalen,* which alters the effect of sunlight upon the skin. 4,5 This substance is one of the active principles of the fruit of Ammi majus Linn, a plant which grows freely in the Nile Delta area. It has been used in Egypt for several centuries in the treatment of vitiligo and is currently being used in this country, among other things, for

Since 1948, new drugs, psoralens (Ammoidin and Ammidin, which are 8-methoxypsoralen and 5-isoamyleneoxypsoralen, respectively), separated in crystalline form from the extracts of the fruits of an Egyptian herb, Ammi majus linn, 1 have been used with success by one of us (A. M. E-M.) in 1948 2,3 and 1949 in the treatment of leukoderma. Since then, many investigators 4-6 have tried these drugs in the treatment of leukoderma, and they have confirmed its successful results. In our trials on these drugs for the last 10 years we were fully aware of the importance of detecting and reporting any undesirable side-effects. The possibility of a potential danger of aggravating a diabetic process was raised when one of us (A. M. E-M., 1952 8 ) reported two cases of mild diabetes where a possible aggravation of their diabetes was clinically suspected. One of these cases was a dentist, treating

Investigation of the aerial parts of the Egyptian medicinal plant Ammi majus L. led to isolation of new coumarin, 6-hydroxy-7-methoxy-4 methyl coumarin (2) and 6-hydroxy-7-methoxy coumarin (3); this is the first time they have been isolated from this plant. The structures of the compounds (2 &3) were elucidated by spectroscopic data interpretation and showed anti-inflammatory and anti-viral activity. Graphical abstract An efficient, one-new coumarin (2) was isolated from the aerial parts of the A. Majus L. was evaluated for their anti-viral and anti-inflammatory activities.