Medicinal plants and medical plant material that contain coumarines

and chromones.

Overview

1. Coumarines definition.2. Classification and structure of coumarines3. Determination of coumarines4. MP and MPM containing coumarines5. Chromone definition6. Classification and structure of chromones 7. Determination of chromones8. 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.

benzo-α-pyrone (coumarin) cis-orto-hydroxycinnamic acid (o-coumaric acid)

Classification and Structure of Coumarins

1.Simple coumarins and glycosides2.Furanocoumarins3.Pyranocoumarins4.Benzocoumarins5.Furanocoumarins6.Isocoumarin7.Complex coumarins

Simple coumarins

Coumarin Dihydrocoumarin

Umbelliferone(7-hydroxy coumarin)

Aesculetin(6,7 – dihydroxy 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)

Visnadin

Seseline type

Benzocoumarins contain a benzene ring

condensated to coumarin at 3,4—arbon atoms.

Ellagic acid

3,4 - benzocoumarin

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 theCompounds.

Qualitative tests on Coumarins

1. Lacton testCoumarins are slowly hydrolysed by dilute alkali form yellow

solution of o-coumaric acid salts. Coumarins regenerate after acidification or saturation by CO2.

2. Azocoupling testThe reaction with diazotization sulfanilic acid in an alkaline enviroment. Red colour develops.

3. Chromatographic methods

Quantitative Determination of Coumarins1. Spectrophotometric2. HPLC3. Gravimetric4. Titration5. Fluorometric6. 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. 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, EuPhMelilot – Melilotus officinalisFabaceaeSyn: 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 fructusParsnip – Pastinaca sativaApiaceae

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

Greater ammi fruits – Ammi majus fructusGreater ammi – Ammi majusApiaceae

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 foliaFigs fruit – ficusi caricae fructus, BPFigs – Ficus caricaMoraceae

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, psoriasisand vitiligo – «Psoberan». Fig fruit preparation are used as a laxative – «Regulax», «Cafiol»

Angelica radix – Angelicae radices, EP, BPAngelica – Angelica archangelica L.ApiaceaeSyn.: 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.ApiaceaeSyn.: 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

1. Simple cromones2. Benzochromones3. Furanochromones and their glycosides4. Pyranochromones5. Hydroxypyranochromones

1. Simple chromones

3-Methylchromone 5,7-Dihydrochromone Aloesin

2. Benzochromone

6,7-benzochromones 7,8-benzochromones

3. Furanochromones

Khellin Visnagin

4. Pyranochromones

Gammaudol Pterochromanol

5. Hydroxypyranochromones

Pteroglycol Pteroxilin

Qualitative tests on Chromones

1. Specific odour.2. Form with alkali solution o-hydroxy-β-diketones without

regeneration of γ-pyrone ring (unlike coumarine).3. Fluorescence in UV-light (blue, yellow, greenish yellow, brown)4. Don’t give Azocoupling test, 2 % solution of aluminium chloride,

with magnesium and concentrated hydrochloric acid (unlike flavonoids).

5. Form coloured compounds with concentrated acid (citric colour), and concentrated alkali (purpe colour).

Pharmacological action

1. Spasmolytic.2. Antibacterial.3. Anticoagulant.4. Analgetic.5. Antiallergic.

MP and MPM containing Chromones

Bishop’s Weed fruit – Visnagae daucoides fructus (Ammi visnagae fructus)Bishop’s Weed – Visnaga daucoides Gaerth., Ammi visnaga (L.)ApiaceaeSyn.: 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 fructusDill – Anethum graveolensApiaceaeSyn.: 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