What are What are phytoestrogensphytoestrogens ??

M. Kurzer, X. Xu, Annu. Rev. Nurt, 1997. 17:353 – 381

Broadly defined, phytoestrogens include isoflavones, coumestanes and lignans. Anumber of these compounds have been identifiedin fruits, vegetables and whole grains commonlyconsumed by humans. Soybeans, clover andalfalfa sprouts and oilseeds are the mostsignificant dietary sources of isoflavones, coumestanes and lignans.

Vitamin D Metabolismus

Interaktion mit Steroidrezeptoren (Östrogen-,

Androgen- and Progesteronrezeptoren) -

selective estrogen rezeptor modulator - SERMs

Inhibierung von Enzymen –

selective enzym modulator – SEMs

Antioxidative Wirkung – total antioxydative capacity

SHBG

antiinflammatoric potential

Pharmacological functions of isoflavonesPharmacological functions of isoflavones

Korrelation Vitamin D Versorgung, Korrelation Vitamin D Versorgung, Phytoöstrogenkonsumation und KrebsinzidenzPhytoöstrogenkonsumation und Krebsinzidenz

Epidemiologische Daten:

höhere Inzidenz von Mamma-, Prostata und

Kolonkarzinom in Länder mit

• weniger Sonneneinstrahlung

• weniger Fischkonsum (beides Vitamin D-Quellen)

• geringer Phytoöstrogenkonsumation

Vitamin D MetabolismusVitamin D Metabolismus • Vitamin D3 bei UV-Einstrahlung in

der Haut produziert• Umwandlung in Leber/Niere durch

Cytochrom P450 Enzyme (CYP27A1 bzw. CYP27B1) in aktiven Hormonmetaboliten 1,25-Dihydroxyvitamin D3

• Zu starke Akkumulation wird durch Abbau bzw. präferentielle 24-Hydroxylierung durch CYP24 vermieden

• Limitierung essentiell für Kalziumhomöostase – aber Nichterreichung nanomolarer Spiegel für antimitotische prodifferenzierende Wirkung von 1,25-D3

Leber

Niere

Inhibierung durch Isoflavone

Induktion durch Isoflavone

Isoflavone bewirken Akkumulation von 1,25-D3

Aus Hesso Farhan et al. 2002 : Isoflavonoids inhibit catabolism of vitamin D

in prostate cancer cells Journal of Chromatography B 777 (2002) 261-268

Vitamin D Metabolismus

Interaktion mit Steroidrezeptoren (Östrogen-,

Androgen- and Progesteronrezeptoren) -

selective estrogen rezeptor modulator - SERMs

Inhibierung von Enzymen –

selective enzym modulator – SEMs

Antioxidative Wirkung – total antioxydative capacity

SHBG

antiinflammatoric potential

Pharmacological functions of isoflavonesPharmacological functions of isoflavones

Vitamin D Metabolismus

Interaktion mit Steroidrezeptoren (Östrogen-,

Androgen- and Progesteronrezeptoren) -

selective estrogen rezeptor modulator - SERMs

Inhibierung von Enzymen –

selective enzym modulator – SEMs

Antioxidative Wirkung – total antioxydative capacity

SHBG

antiinflammatoric potential

Pharmacological functions of isoflavonesPharmacological functions of isoflavones

Aromatase

5-Reductase

Sulfatase

Die wichtigsten Enzyme für SEMsDie wichtigsten Enzyme für SEMs

HERMANN ADLERCREUTZ ET AL. J. Steroid Biochem. Molec. Biol. Vol. 44, No. 2, pp. 147-153, 1993

Summary – Isoflavonoid phytoestrogens and lignans in plants are known to be consistuents of animal and human food .........................are moderate or weak inhibitors of human estrogen synthase (aromatase) and.......The inhibition is competitive with respect to testosterone and androstenedione,......

B A J EVANS ET AL.,. Journal of Endocrinology (1995) 147, 295 - 302

....This report describes the inhibition of 5-reductase and 17ß-hydroxysteroid dehydrogenase by six isoflavonoids and....... In genital skin fibroplasts, genistein, biochanin A and equol were the most potent inhibitors of 5-reductase activity........ It is possible that a life-long dietary exposure to these lignans and isoflavones may have a significant influence on the development of hormone-dependent tumors.

Vitamin D Metabolismus

Interaktion mit Steroidrezeptoren (Östrogen-,

Androgen- and Progesteronrezeptoren) -

selective estrogen rezeptor modulator - SERMs

Inhibierung von Enzymen –

selective enzym modulator – SEMs

Antioxidative Wirkung – total antioxydative capacity

SHBG

antiinflammatoric potential

Pharmacological functions of isoflavonesPharmacological functions of isoflavones

AntiRadicalPower

0

1

2

3

4

5

6

7

8

ARP

Red Clover extract

Soybean preparation

RadikalfängerkapazitätRadikalfängerkapazität 

sampleARP

(=antiradical power)

red clover plant sample 20

red clover extract 7

soy isoflavones capsules 2

 

Quelle: 2002 Annual Meeting and Food Expo – Anaheim, California

Photochem Photobiol 2001 Sept; 74(3):465 - 70

Isoflavonoid compounds from red clover (Trifolium pratense)Isoflavonoid compounds from red clover (Trifolium pratense)protect from inflammation and immune suppression inducedprotect from inflammation and immune suppression inducedBy UV radiationBy UV radiation

Widyarini S, Spinks N, Husband AJ, Reeve VE.Widyarini S, Spinks N, Husband AJ, Reeve VE.Faculty of Veterinary Science, University of Sydney, NSW 2006, AustraliaFaculty of Veterinary Science, University of Sydney, NSW 2006, Australia ..

Isoflavones derived from many edible plants have been reported to possessIsoflavones derived from many edible plants have been reported to possesssignificant antioxidant, estrogenic and tyrosine kinase inhibitory activity.significant antioxidant, estrogenic and tyrosine kinase inhibitory activity.Genistein has been found previously to provode protection from oxidativeGenistein has been found previously to provode protection from oxidativedamage induced by UV radiation both in vitro and following dietarydamage induced by UV radiation both in vitro and following dietaryadministrationadministration. .

Vitamin D Metabolismus

Interaktion mit Steroidrezeptoren (Östrogen-,

Androgen- and Progesteronrezeptoren) -

selective estrogen rezeptor modulator - SERMs

Inhibierung von Enzymen –

selective enzym modulator – SEMs

Antioxidative Wirkung – total antioxydative capacity

SHBG

antiinflammatoric potential

Pharmacological functions of isoflavonesPharmacological functions of isoflavones

Szabo L. USA Today Nov.10,2004;8DSzabo L. USA Today Nov.10,2004;8D

RESVERATROL RESVERATROL

JAHRJAHRPUBLIKATIONENPUBLIKATIONEN

20002000 147147 20012001 214214 20022002 238238 20032003 318318 20042004 870870

Pharmakologische Wirkungen von Resveratrol:Pharmakologische Wirkungen von Resveratrol:

• Direkte und indirekte gefäßerweiternde WirkungDirekte und indirekte gefäßerweiternde Wirkung• HDLHDL↑, LDL↓↑, LDL↓• Hemmung der ThrombozytenaggregationHemmung der Thrombozytenaggregation• Hemmt die Entstehung von Krebszellen und auch deren Hemmt die Entstehung von Krebszellen und auch deren

Entwicklung (Brust, Darm, Prostata, Haut, Lunge)Entwicklung (Brust, Darm, Prostata, Haut, Lunge)• Antitumorwirkung Antitumorwirkung • Entzündungshemmend (COX1 und COX2)Entzündungshemmend (COX1 und COX2)• Starkes Antioxidans (sowohl fett als auch wasserlöslich)Starkes Antioxidans (sowohl fett als auch wasserlöslich)• Dosisabhängige östrogene EffekteDosisabhängige östrogene Effekte• Lebensverlängerung von Zellen (Anti Aging)Lebensverlängerung von Zellen (Anti Aging)

Summary:Summary:

Phytoestrogens (like isoflavones, Phytoestrogens (like isoflavones, resveratrol) in aspect of age-resveratrol) in aspect of age-prevention are substances to prevention are substances to

minimize the risk of oxydation and minimize the risk of oxydation and inflammation.inflammation.

Isoflavones are under certain Isoflavones are under certain circumstances an interesting circumstances an interesting

alternative to HT.alternative to HT.