Transcript Medicinal plants and medical plant material that contain coumarins

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 Ohydroxycinnamic 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 glycosides
2.Furanocoumarins
3.Pyranocoumarins
4.Benzocoumarins
5.Furanocoumarins
6.Isocoumarin
7.Complex coumarins
Simple coumarins
Dihydrocoumarin
Coumarin
Aesculetin
Umbelliferone
(7-hydroxy coumarin)
(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)
Seseline type
Visnadin
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 the
Compounds.
Qualitative tests on Coumarins
1. 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
1.
2.
3.
4.
5.
6.
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-Oglucosyloxycinnamic 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-7hydroxycoumarin) 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, 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 cisand 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
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 βphellandrenes, 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
1. Simple cromones
2. Benzochromones
3. Furanochromones and their glycosides
4. Pyranochromones
5. 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.
2.
3.
4.
5.
Spasmolytic.
Antibacterial.
Anticoagulant.
Analgetic.
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.)
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 (2,54,0 %): 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