Potential Health-modulating Effects of Isoflavones and Metabolites via Activation of PPAR and AhR

Isoflavones have multiple actions on cell functions. The most prominent one is the activation of estrogen receptors. Other functions are often overlooked, but are equally important and explain the beneficial health effects of isoflavones. Isoflavones are potent dual PPARα/γ agonists and exert anti-inflammatory activity, which may contribute to the prevention of metabolic syndrome, atherosclerosis and various other inflammatory diseases. Some isoflavones are potent aryl hydrocarbon receptor (AhR) agonists and induce cell cycle arrest, chemoprevention and modulate xenobiotic metabolism. This review discusses effects mediated by the activation of AhR and PPARs and casts a light on the concerted action of isoflavones

Aryl hydrocarbon receptor activity of plant extracts

Der Arylhydrocarbon Rezeptor (AhR) ist ein wichtiger Regulator von physiologischen Prozessen, darunter die Zellzykluskontrolle und Reproduktion. Ein tieferes Verständnis von Substanzen, die den AhR aktivieren und Identifikation noch unbekannter AhR Aktivatoren, die umweltverschmutzende Chemikalien aber auch natürliche Pflanzen- und Lebensmittelinhaltsstoffe sein können, könnten die Ausgangssubstanzen für die Behandlung von Krebs, Wechseljahrsbeschwerden und hormonell-abhängiger Erkrankungen sein. Es wurden Extrakte essbarer Pflanzen, Lebensmittelinhaltsstoffe, sowie ausgewählte Pestizide, die potentiell in Lebensmitteln vorkommen können, untersucht. Rotklee ist ein potenter Aktivator des humanen AhR. Der Wirkung konnten chemische Strukturen zugewiesen werden, nämlich den potenten AhR Liganden Formononetin und Biochanin A. Auch aus Sauerkraut konnte eine neue Verbindung, Indolylfuran (1-(2-furanyl)2-(3-indolyl)ethanon), isoliert werden, die ein starker AhR Ligand ist. Sauerkrautextrakt und Indolylfuran zeigten in vivo antiöstrogene Wirkung. In dieser Studie konnten auch grundlegende Wechselwirkungen zwischen dem AhR und dem Östrogenrezeptor (ER) aufgeklärt werden. Eine AhR-Aktivierung kann auch durch unsachgemäße Anwendung von Pestiziden erfolgen. Nicht-persistene Pestizide, die in der Obstkultivierung und dem Weinbau verwendet werden, wurden untersucht, ob sie über nukleäre Rezeptoren, wie AhR, ER und dem Androgenrezeptor (AR), das hormonelle Gleichgewicht beeinflussen können. Einige Pestizide zeigten in vitro diese Wirkung, aber bei einer Anwendung entsprechend den gesetzlichen Richtlinien, werden nicht jene Konzentrationen erreicht, die so einen Effekt auslösen können. Da aber die Exposition von Landarbeitern und der Landbevölkerung durchaus höher ist, kann eine Beeinflussung des Hormonhaushaltes nicht ausgeschlossen werden. Zusammenfassend kann man sagen, dass Lebensmittel das Potential haben den AhR und die von ihm regulierten Stoffwechselwege zu beeinflussen.The aryl hydrocarbon receptor (AhR) is an important regulator of several physiological processes including cell cycle regulation and reproduction. A dysregulated AhR signalling can lead to severe diseases due to homeostatic imbalance. Deeper insights of the impact of the AhR pathway, but also the knowledge of possible AhR activators that can be found in the environment as pollutants but also in plants and normal diet, facilitate the use of the AhR as drug target in cancer therapy, menopausal complaints and hormone-dependent diseases. In this study, edible plants, food ingredients but also possible food contaminations such as pesticides were tested for their ability to transactivate the AhR. Red clover and sauerkraut were identified as potent activators of the human AhR. This was further elucidated by the identification of red clover compounds formononetin and biochanin A and the novel sauerkraut ingredient 1-(2-furanyl)2-(3-indolyl)ethanone, common name indolylfuran, as potent AhR agonists. Sauerkraut and indolylfuran showed in vivo anti-estrogenic effects. This study showed also basic interactions of the AhR with the estrogen receptor (ER). Activation of the AhR can also be caused by food contaminants such as pesticide residues. Non-persistent pesticides, commonly used in fruit and wine cultivation, were tested for their ability to transactivate receptor pathways affecting hormonal balance such as the AhR, the ER and androgen receptor (AR). Several pesticides were identified that activate AhR, ER and AR. Application within legally permitted doses does not reach concentrations that can disturb hormonal balance of fruit and wine consumers. Nevertheless, this assumption bases only on in vitro data. The exposure of rural population and farm workers is higher, so that an impact on hormonal pathways cannot be excluded. It can be concluded that diet has indeed the potential to affect the AhR pathway and to hereby modulate AhR regulated physiological functions.vorgelegt von Svjetlana MedjakovicAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersWien, Univ. für Bodenkultur, Diss., 2010OeBB(VLID)193062

Lupinalbin A as the most potent estrogen receptor α- and aryl hydrocarbon receptor agonist in Eriosema laurentii de Wild. (Leguminosae)

Background: Eriosema laurentii De Wild. (Leguminosae) is a plant used in Cameroon against infertility and gynecological or menopausal complaints. In our previous report, a methanol extract of its aerial parts was shown to exhibit estrogenic and aryl hydrocarbon receptor agonistic activities in vitro and to prevent menopausal symptoms in ovariectomized Wistar rats. Methods: In order to determine the major estrogen receptor α (ERα) agonists in the extract, an activity-guided fractionation was performed using the ERα yeast screen. To check whether the ERα active fractions/compounds also accounted for the aryl hydrocarbon receptor (AhR) agonistic activity of the crude methanol extract, they were further tested on the AhR yeast screen. Results: This study led to the identification of 2′-hydroxygenistein, lupinalbin A and genistein as major estrogenic principles of the extract. 2′-hydroxygenistein and lupinalbin A were, for the first time, also shown to possess an AhR agonistic activity, whereas genistein was not active in this assay. In addition, it was possible to deduce structure-activity relationships. Conclusions: These results suggest that the identified compounds are the major active principles responsible for the estrogenic and AhR agonistic activities of the crude methanol extract of the aerial parts of Eriosema laurentii