FLAVONOIDE O

O O 2
▪ subst. de natura vegetala 3

▪ deriv. de 2 - fenil - benzopiran

▪ pigmenti din flori, fructe, frunze
croman flavan izoflavan
▪ peste 9000 compusi (benzopiran)
(2-fenil-benzopiran) (3-fenil-benzopiran)
▪ frunze tinere, muguri, boboci florali
▪ agliconi, O-glicozide, C-glicozide

▪ componente ale dietei (209-1017 mg/zi) – fructe, ceai, vin rosu, legume, ciocolata (bioflavonoide) factor (vitamina) P

▪ Bryophytae ▪ Pteridophytae
▪ atractanti pentru insecte ▪ Gymnospermae
▪ protectie fata de UV ▪ Asteraceae Urticaceae Euphorbiaceae
▪ coenzime Ericaceae Amentaceae Polygonaceae
▪ rol in crestere, dezvoltare Malvaceae Rubiaceae Sterculiaceae
▪ fitoalexine (izoflavone) Rosaceae Apiaceae Rutaceae
Myrtaceae Apocynaceae Verbenaceae
 GLUCIDE
Ciclul
fotosintezei glicocol ALCALOIZI

Triptofan ALCALOIZI
Glicerina

Ac. piruvic Ac. sikimic Fenilalanina ALCALOIZI

TANINURI CUMARINE
AC. GRASI
LIGNANE
Acetil-CoA
FLAVONOIDE
TERPENE
Ciclul Krebs lizina, ornitina ALCALOIZI
ANTRADERIV.

NAFTODERIV. AC. GLICOZIDE TIOGLICOZIDE

FLOROGLUCIDE ORGANICI CIANOGENETICE
 R OH R O R O R
3' OH ox.
4'
2'
8 1 1' 5'
HO 7 O 2
6' O O O
3
6 4
calcona flavanona flavona
5
OH O
ox. ox.

FLAVONE
O R O R O R
R=H apigenol red.
R=H luteol
OH OH
OH
izoflavonoida
O O
catehina
flavanonol flavonol
ox.
red. red.

flobafene
+
O R O R
neoflavonoida
OH OH
OH
antocian
leucoantocian
 OH OH OH
OH OH OH
+
HO O HO O HO O

OR OR OR
OH O OH OH
rutozida cianozida leucocianozida
galbena rosie incolora
OH
OH
OH
O]2 Ca HO O
O
O
HO O OH
HO O
OH
OR catehina
OR incolora
OH
OH
fenolat
albastru forma chinonica flobafene
violeta rosii
 Albert Szent-György
act. angioprotectoare (1893-1986)
act. angioactivatoare 1937 – Premiul Nobel
act. antiinflamatoare ... procesul combustiei biologice cu referire speciala
la vitamina C si catabolismul acidului fumaric
act. antiedematoasa
act. antiaterosclerotica
citrina = vitamina P (factor P)
act. coronarodilatatoare
act. antiagregant plachetara

act. hepatoprotectoare act. anxiolitica act. anbacteriana

act. hepatoregeratoare act. sedativa act. antifungica
act. antihepatotoxica act. neuroprotectoare act. antivirala
act. antifibrotica

act. antialergica act. antidiabetica

act. spasmolitica
act. diuretica act. estrogen-like
RUTOZIDA (RUTIN, SOFORINA)

Sophorae flos Fagopyri herba Eucalypti folium

Sophora japonica Fagopyrum esculentum Eucalyptus macrorhyncha
Fabaceae Polygonaceae Myrtaceae
Gl
salcam japonez hrisca
12-10% (20-34%) 2-8% 10%
Ra

3’,4’,5,7-tetrahidroxi-flavon-3-rutinozida
◼ indicatii:

◼ actiune: fragilitate capilara

diateze hemoragice
vasoprotectoare (capilaroprotectoare) antidiabetica
insuficienta venoasa
antiagregant plachetara (antitrombotica) antitumorala
hemoroizi
antiinflamatoare antioxidanta
hemoptizie
antialergica neuroprotectoare
antimicrobiana
afectiuni intestinale inflamatorii
(colita ulceroasa, boala Crohn)
act. vasoprotectoare/capilaroprotectoare act. antialergica
↑ rezistenta, ↓ permeabilitatea ↓ histamina, LT

consolidare perete capilar ↓ TNF-alfa, IL-4, -5, -17

↓ hialuronidaza, colagenaza, elastaza ↓ MIP-2, VEGF, caspaza-1

↓ histamina
↓ oxidarea ac. ascorbic act. antioxidanta
↓ oxidarea adrenalinei ↓ SRO, SRN, ox. LDLc
↓ COMT chelatarea metalelor tranzitionale
↓ PGE2, LT, TXA2, PAF

act. antiagregant plachetara (antitrombotica) act. antimicrobiana

↓ sinteza proteica, integritatea peretelui bacterian
↓ TXA2, PAF
↓ factori de virulenta
↓ act. tromboplastinei
↑ heparina
act. chemopreventiva
act. antiinflamatoare
efecte apoptotice, antiproliferative, antiangiogenice
↓ NF-kB, COX-2, 5-LOX, iNOS, IL-6,
sistem complement, enzime lizozomale, mieloperoxidaze
◼ mod de administrare:
trihidroxietilrutozida

oral: 120-240 mg (500 mg)/zi (3 prize) (oxerutin)

topic: preparate cu 2% rutozida (2 ori/zi)

oral: topic:
◼ contraindicatii:
0,9-1,2 g/zi – insuf. venoasa (hemoroizi) preparate cu 2% oxerutin
hipersensibilitate la produs
3 g/zi – edem limfatic
sarcina, alaptare 1,2-2,4 g/zi – retinopatie diabetica
0,6-2 g/zi – afectare cutanata/mucoase (radioterapie)
2 sapt. de tratament
reactii adverse (rare):
20 mg rutozida
iritatie gastrica, diaree
50 mg ac. ascorbic
aceleasi contraindicatii eruptii cutanate, prurit
ameteli
▪GINKOR FORT ® - caps.

extract Ginkgo biloba 14 mg

heptaminol clorhidrat 300 mg

troxerutin 300 mg

4 cps./zi-5 zile, 2 cps./zi-5 zile – criza hemoroidala; 2 cps./zi

▪ MEDOXERUTIN - gel 2%

▪ TROXERUTIN – caps. 300 mg, gel 2%, crema 2%

▪ TROXEVASIN ® - caps. 300 mg, gel 2%

▪ TROXSAL ® GEL 2%

▪ VENORUTON ® - caps. 300 mg, gel 4%

▪ VENOTON ® - caps. - 200 mg troxerutin + 100 mg ac. ascorbic, gel 2%

▪ RUTOVEN – draj. 300 mg, crema 2%

HESPERIDOZIDA (HESPERIDINA) DIOSMINA citrusbioflavonoide (Citrus sp.)

hesperidol diosmetina C. sinensis

C. limon
C. reticulata
C. bergamia

Agathosma betulina (sin. Barosma betulina)

Rutaceae

◼ actiune:

vasoprotectoare (capilaroprotectoare)
chemopreventiva, antitumorala
protejarea endoteliului vascular

antioxidanta, antiinflamatoare act. venotonica

hipolipemianta, antiaterosclerotica act. antiedematoasa

antiagregant plachetara ameliorarea (micro)circulatiei sanguine si limfatice
antimicrobiana
 act. antiinflamatoare
act. vasoprotectoare
↓ COX-2, iNOS, IL-1beta, -2, -4, -6, TNF-alfa (MAPK), MMP
↓ adeziunea leucocitara
↓ MMP
↑ tonus venos (NA) act. antiaterosclerotica
act. antioxidanta act. hipolipemianta (↓ C, TG, LDLc)
↓ permeabilitatea, ↑ rezistenta peretelui vascular (↓ 3-hidroxi-3-metil-glutaril-CoA reductaza, acil-CoA colesterol-aciltransferaza)

↓ proliferarea cel. musculare netede vasculare

act. antitrombotica (↓ TXA2)

◼ indicatii:
◼ mod de administrare:
insuficienta venoasa cronica
- fractiune flavonoidica micronizata (oral, topic)
insuficienta limfatica
- 450 mg diosmina si 50 mg hesperidina
fragilitate capilara
- 500 mg x 2/zi (8 sapt.); 500 mg x 6-4/zi
hemoroizi
- crema cu 5% diosmina
metroragii (dispozitive intrauterine)
1 tableta/zi

- Afine (extract 80:1 din fruct de Vaccinium myrtillus – 2mg) (echivalent 500 μg antocianozide) 160 mg
- Gotu kola (extract 4:1 de Centella asiatică – 25 mg) 100 mg
- Castan sălbatic (extract 6:1 Aesculus hippocastanum – 166,7 mg) (echivalent 33,3 mg aescină) 1000 mg
- Ghimpe (extract 4:1 de Ruscus aculeatus – 200 mg) 800 mg
- Vitamina C 250 mg
- Hesperidină 100 mg
 Citrus paradisi

bergamotina dihidroxi-bergamotina naringina

 NU:
- citostatice – lapatinib, nilotinib → torsade de pointes, mielotoxicitate
- agenti antiinfectiosi – chinina, primaquine
- hipocolesterolemiante – simvastatin, atorvastatin → rabdomioliza
 CYP3A4, glicoproteina P
- medicatie cardiovasculara – clopidogrel, felodipin, amiodarona, ticagrelor
- medicatie SNC – fentanil, ketamina, oxicodona, triazolam
- antiemetice - domperidona
- imunosupresoare – ciclosporina, tacrolimus
- medicatia tractului urinar – solifenacin, darifenacin, tamsulosin
- etinilestradiol
CRATAEGI FOLIUM ET FLOS / FRUCTUS

◼ Crataegus monogyna Rosaceae paducel, maracine, gherghinar

◼ Crataegus laevigata (sin. C. oxyacantha, C. oxyacanthoides)

hibrizi

C. nigra
C. pentagyna
C. azarolus

paducel
laptele batranilor
◼ compozitie chimica (Crataegi folium cum flore):

compusi flavanici (1-3%) O-glicozide flavonice (1-2%) C-glicozide flavonice (1%)

proantocianidoli

(epi)catehina
dimeri (B1-B5)
trimeri (C1, C2) vitexina
hiperozida
tetrameri (D1)

ac. triterpenici pentaciclici (crategolic, ursolic, oleanolic)

Gl izovitexina
steroli
ac. (poli)fenolici (cafeic, ferulic, clorogenic)
amine (di-, trimetilamina, colina, acetilcolina)
vitamine (B1, C)

orientina
fructe: ↓ deriv. flavonici si PA; ↑ antociani, carbohidrati, ac. organici

OH

HO O
OH
4
OH
OH
OH
OH
HO O
OH HO O
8 OH
4
OH 4
catehina OH
OH
OH OH

HO O OH
8 OH
HO O
OH 8 OH
OH proantocianidol B2
OH
OH

proantocianidolul C1

epicatehina
◼ actiune: act. cardiotonica act. antiaritmica act. coronarodilatatoare

act. de protectie a endoteliului vascular act. antiagregant plachetara

act. antihipertensiva

act. sedativa act. spasmolitica act. diuretica act. hipolipemianta

- efect inotrop + (forta de contractie)

- efect cronotrop + (frecventa cardiaca)
- efect dromotrop + (viteza de conducere AV)
- efect batmotrop – (excitabilitatea miocardica)

- ↓ Na+,K+-ATP-aza, ↑Ca2+
- ↓ canale K+
- act. antioxidanta (↓ peroxidare lipidica, ↑SOD, CAT, GPx)
- ↓ TXA2
- regenerarea endoteliului vascular (↑ sinteza colagen)
 ◼ indicatii: ◼ reactii adverse (rare):

tulburari digestive
insuficienta cardiaca (II, NYHA – New York Heart Association)
ameteli
cord pulmonar
cefalee
cardiomiopatie
palpitatii
angina pectorala
nevroza cardiaca
hipertensiune arteriala
◼ contraindicatii:
ateroscleroza
hipersensibilitate
sarcina, alaptare, copii sub 12 ani
◼ mod de administrare: oral

300-900 mg extract/zi (12-15 mg hiperozida/zi)

◼ atentie: asociere cu
240-560 mg extract/zi (45-90 mg oligomeri PA/zi)
medicatia cardiotonica

600-900 mg extract/zi, 200 mg extract/doza, 2-3 prize medicatia antianginoasa

min. 6 sapt. medicatia antihipertensiva

LI 132
extract uscat din frunze si flori
solvent de extractie : metanol 70%
raport produs vegetal : extract uscat = 5,5 : 1
2,25% flavonoide (exprimate in hiperozida) si 11,3% proantocianidoli
Lichtwer Pharma (Berlin, Germania) - FAROS® 300.

WS 1442
extract uscat din frunze si flori
solvent de extractie : etanol 45%
raport produs vegetal : extract uscat = 4 – 6,6 : 1
18,75% oligomeri proantocianidolici
Dr. Willmar Schwabe Pharmaceuticals (Karlsruhe, Germania) - CRATAEGUTT®.
 STUDII CLINICE

900 mg extract ~ 37,5 mg captopril

insuficienta cardiaca NYHA II

160 – 900 mg extract / zi

efecte adverse – RARE (sub 4%)
1 – 4 luni
tulburari gastrointestinale, migrena, vertij,
WS 1442 (45% etanol, RDE: 4-7 : 1,
inrosirea fetei
18,75% oligomeri proantocianidolici)

NYHA II
 rezistenta la efort fizic
160 – 900 mg extract hidroalcoolic /zi, 2-3 prize
 interval de timp necesar atingerii pragului anaerob
(600 – 900 mg/zi, 1800 mg/zi)

 fractia de ejectie ~ 4 – 30 mg flavonoide

~ 30 – 160 mg proantocianidoli oligomeri

 starea generala a pacientilor
cel putin 6 sapt.
- camfor 2,5 g
- extr. fluid fructe proaspete paducel
(etanol 93%, 1 : 1,3-1,5) 97,3 g
- mentol 0,2 g

10-25 pic. x 3/zi