Medicinal plants and medical plant material that contain coumarines and chromones.

Overview 1. Coumarines definition. 2. Classification and structure of coumarines 3. Determination of coumarines 4. MP and MPM containing coumarines 5. Chromone definition 6. Classification and structure of chromones 7. Determination of chromones 8. MP and MPM containing chromones

Coumarins - are natural biological active substances, at the base of which there lies system of benzo-α-pyrone (the lactone of O-hydroxycinnamic acid) and possessing antispasmodic, anticoagulant, coronary vasodilatory and other effects. cis-orto-hydroxycinnamic acid (o-coumaric acid) benzo-α-pyrone (coumarin)

Classification and Structure of Coumarins Simple coumarins and glycosides Furanocoumarins Pyranocoumarins Benzocoumarins Isocoumarin Complex coumarins

Simple coumarins Dihydrocoumarin Coumarin Aesculetin Umbelliferone (6,7 – dihydroxy coumarin) Umbelliferone (7-hydroxy coumarin) Scopoletin (6-methoxy-7-hydroxy-coumarin)

Furanocoumarins  consists of a 5-membered furan ring attached to the coumarin nucleus, Psoralen (furo-2’,3’ : 7, 6-coumarin) Angelicin (isopsoralen) (furo-2’,3’ : 7,8 –coumarin) Bergapten

Pyranocoumarins 2’,2’ – dimethylxanthyletin (2’,2’ – dimethylpyran-5’,6’ : 6,7-coumarin) Seseline type Visnadin

Benzocoumarins  contain a benzene ring condensated to coumarin at 3,4—arbon atoms. Ellagic acid 3,4 - benzocoumarin

Isocoumarin is a isomer of coumarin Furanobenzocoumarins  contain benzofuran condensated to coumarin at 3,4-carbon atoms Coumoestrol Isocoumarin is a isomer of coumarin

Physical and chemical properties of Coumarins They occur as colourless crystals. Coumarins have a characteristic fragrant odour and bitter, aromatic and burning taste. They are soluble in ethanol, methanol, chloroform, fatty oil, alkaline water solution. In ammoniacal solution these compounds have a blue, blue-green or violet fluorescence. The fluorescence is marked if examined in filtered Ultraviolet light and is used for the chlomatographic visualization of the Compounds.

Qualitative tests on Coumarins Lacton test Coumarins are slowly hydrolysed by dilute alkali form yellow solution of o-coumaric acid salts. Coumarins regenerate after acidification or saturation by CO2.

2. Azocoupling test The reaction with diazotization sulfanilic acid in an alkaline enviroment. Red colour develops. 3. Chromatographic methods

Quantitative Determination of Coumarins Spectrophotometric HPLC Gravimetric Titration Fluorometric Polarographic

Coumarin itself has been found in about 150 species belonging to over 30 diff'erent families. Although it is probably present in the undamaged plants as trans-O-glucosyloxycinnamic acid. Enzyme activity in the damaged tissue leads to a loss of glucose and a trans→cis isomerization foliowed by ring closure. Coumarin gives a characteristic odour of new-mown hay and occurs in many Leguminosae (Fabaceae) such as melilot and tonco beans. It is also recorded in woodruff. Asperula odorata (Rubiaceae).

Medical application of Coumarins Coumarins are characterized with photosynthetizing (Fructus Psoraleae, Fructus Ammi majoris, Folia Ficusi carici), spasmolytic (Fructus Pastinacae), P-vitaminic (Semina Hippocastani) action. As individual substance coumarins possess anticoagulant (dicoumarol), antimicrobic (umbelliferone), estrogenic (coumestrols of Trifolium spp, Fabaceae), antitumour (ostol) action. Some coumarin derivatives still find application for their anticoagulant properties. Bishydroxycoumarin or dicumarol is a drug related to coumarin. Dicumarol is an anticoagulant. It was obtained originally from improperly cured leaves and flowering tops of Melilotus officinalis (Linne) Pall. (Fam. Fabaceae), but it is now prepared synthetically. Sweet clover extract is used for the symptomatic treatment of venous and lymphatic vessel insufficiency.

The antispasmodic activity of the barks of Viburnum prunifolium Linne (blackhaw) and V. opulus Linne (true cramp bark) (Fam. Caprifoliaceae) has been attributed to scopoletin (6-methoxy-7-hydroxycoumarin) and other coumarins. Some furanocoumarins are photosensitizers, therefore they are indicated for the therapy of psoriasis and vitiligo. Psoralens are photosensitizing furocoumarins that occur in a number of plant families, including the Apiaceae and Rutaceae, where they are a common cause of phototoxicity. Methoxsalen, 8-methoxypsoralen, or xanthotoxin, a constituent of the cremocarps of Ammi majus Linne (Fam. Apiaceae), is used to facilitate repigmentation in idiopathic vitiligo (leukoderma) and for symptomatic control of severe, disabling psoriasis. Visnadin, a pyranocoumarin isolated from khella, has been extracted and marketed for its coronary vasodilator effect    

Khellin is a furochromone found in the fruit of Ammi visnaga Lam. (Fam Khellin is a furochromone found in the fruit of Ammi visnaga Lam. (Fam. Apiaceae). The plant grows in Mediterranean countries and has been used for urethral spasm and renal colic. Khellin is a potent coronary vasodilator and bronchodilator in the treatment of coronary insufficiency, angina pectoris, and bronchial asthma.

MP and MPM containing coumarins

Melilot herb - Meliloti herba, EuPh Melilot – Melilotus officinalis Fabaceae Syn: King’s Clover, Yellow Sweet Clover, Hay Flowers, Wild Laburnum According to the EP, the content minimum 0,3 % of coumarin. Constituents: free coumarins (0,4-0,9 %), furthermore 3,4-dihydrocoumarin, melilotol, melilotin; hydroxycoumarins, including among others umbelliferone, scopoletin, herniarin, fraxidin; flavonoids: kampferol- and quercetin glycosides; triterpene saponins, volatile oils. Useses. The drug is used internally for problems arising from chronic venous isufficiency, such as pain and heaviness in legs, night cramps in legs, itching and swelling; for the supportive treatment of trombophlebitis, postthrombotic syndromes, haemoroids. The composition medicine cardiophit (cardioprotective remedy)

Parsnip fruit – Pastinacae sativae fructus Parsnip – Pastinaca sativa Apiaceae Constituents: furocoumarins are in particular angelicin, bergaptene, xanthotoxin, imperatorin, psoralen; volatile oilis chief components of cis- and trans- β-ocimene, trans-β-farnesene; flavonoids, including rutin Uses. The fruits are used in kidney and gastrointestinal complaints and for digestion problems. Produced photosensitizing medicines: psoralenum, beroxan (the mix of bergaptene and xantoxin). Smasmolitic drug that effects on effect on coronary vessels and prevents stenocardia - pastynacyn

“Amifurine”, Anmarinum gel Greater ammi fruits – Ammi majus fructus Greater ammi – Ammi majus Apiaceae Syn.: Bishopsweed, Bullwort, Lady’s lace Constituents: furocoumarins are derivatives from psoralene: xanthotoxin, imperatorin, bergapten; protein, fixed oil Uses: Medicines is used in photochemotherapy to treat a number of skin disorders, including mycosis fungoides, psoriasis and vitiligo. “Amifurine”, Anmarinum gel

Figs leaf – Ficusi caricae folia Figs fruit – ficusi caricae fructus, BP Figs – Ficus carica Moraceae Constituents: leaves – furanocoumarins, including psoralen, bergaptene; volotile oil; flavonoids, incl. rutin, Fructus – fruit acids: citric acid, malic acid; monosaccharides and oligosaccharides (approximatly 50 %), to some extent transformed into inverted sugar. Uses. Medicines from leaves are used in photochemotherapy to treat a number of skin disorders, including mycosis fungoides, psoriasis and vitiligo – «Psoberan». Fig fruit preparation are used as a laxative – «Regulax», «Cafiol»

Angelica radix – Angelicae radices, EP, BP Angelica – Angelica archangelica L. Apiaceae Syn.: European angelica, Angel’s wort Content : minimum 2.0 ml/kg of essential oil (dried drug). Constituents. Volatile oil: chief components are α- and β-phellandrenes, α-pinenes, macrociclic lactone; furanocoumarins, inc. bergaptene, xanthotoxin, scopoletin, umbelliferone, archangelicin; caffeic, chlorogenic acids; flavonoids; tannins archangelicin Uses. Medicines are used as antispasmodic, cholagogic and stimulatory for secretion of gastric juice, at dyspeptic complants, loss of appetite. ( Doppelherz Energietonikum)

Wild carrot fruits - Dauci carotae fructus, BH (1996) Wild carrot – Daucus carota L. Apiaceae Syn.: Bird’s neat, Bird’s nest Constituents. Coumarin: umbelliferone, esculetin, scopoletin; furanocoumarin 8-methoxypsoralen a 5-methoxypsoralen; flavones (apigenin, chrysin, luteolin), flavonols (e.g. kaemferol, quercetin) and verious glycosides, carotinoids, valotile oil (very little); mono and oligosaccharides: glucose, saccharose. Uses. Wild carrot is stated to possess diuretic, spasmolitic and carminative properties. Traditionally, it has been used for urinary calculus, lithuria, cystits, gout, and specifically for urinary gravel or calculus. Urolesanum

Chromone Chromone – are natural biological active substances the general formula is C6-C3, at the base of 9,10-benzo-γ-pyrone.

Classification Simple cromones Benzochromones Furanochromones and their glycosides Pyranochromones Hydroxypyranochromones

1. Simple chromones 3-Methylchromone 5,7-Dihydrochromone Aloesin

6,7-benzochromones 7,8-benzochromones

3. Furanochromones Khellin Visnagin

Gammaudol Pterochromanol 4. Pyranochromones Gammaudol Pterochromanol

5. Hydroxypyranochromones Pteroglycol Pteroxilin

Qualitative tests on Chromones Specific odour. Form with alkali solution o-hydroxy-β-diketones without regeneration of γ-pyrone ring (unlike coumarine). Fluorescence in UV-light (blue, yellow, greenish yellow, brown) Don’t give Azocoupling test, 2 % solution of aluminium chloride, with magnesium and concentrated hydrochloric acid (unlike flavonoids). Form coloured compounds with concentrated acid (citric colour), and concentrated alkali (purpe colour).

Pharmacological action Spasmolytic. Antibacterial. Anticoagulant. Analgetic. Antiallergic.

MP and MPM containing Chromones

‘Avisan’, “Celin’’. “Marelin”, “Phitolit” Bishop’s Weed fruit – Visnagae daucoides fructus (Ammi visnagae fructus) Bishop’s Weed – Visnaga daucoides Gaerth., Ammi visnaga (L.) Apiaceae Syn.: Khella, Toothpickweed. Constituents. Furochromones are particularly khellin, visnagin, khellol and khellol glicoside; pyranocoumarins – visnadin and samidin; furanochromones; flavonoids – quercetin and isohamnetin and their 3-sulfates; volotile oil; fatty acids. Uses. The drug intensifies coronary and myocardial circulation acting as a mild positive ionotrope. It has antispasmodic effect on smooth muscles – ‘Avisan’, “Celin’’. “Marelin”, “Phitolit”

Dill fruit – Anethi graveolentis fructus Dill – Anethum graveolens Apiaceae Syn.: Dilly Constituents. Furanochromones are visnagin, khellin; furanocoumarins, inc. bergaptene; hydroxycoumarins: umbelliferone; volotile oil (2,5-4,0 %): chief constituents are carvone (approx. 50 %), dill apiole, (+) – limonene; fatty oil; phtalides. Uses. The fruit of the Dill plant an antispasmodic effect on the smooth muscles of the gastrointestinal tract, and a bacteriostatic effect. “Anetin”

Thanx for the attention