Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design
2021
Autori:
Ajdžanović, VladimirMiler, Marko
Šošić-Jurjević, Branka
Filipović, Branko
Milenković, Dragan
Jakovljević, Vladimir
Milošević, Verica
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
,
© 2021 Elsevier Ltd.
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
In a series of our previous works, we revealed the beneficial effects of applied soy isoflavones (genistein or
daidzein) on the wide context of corticosteroidogenesis in vivo, in a rat model of the andropause. Soy isoflavones
decreased the circulating levels of pituitary adrenocorticotropic hormone, inhibited aldosterone secretion, as
well as corticosterone production and secretion, but stimulated dehydroepiandrosterone secretion, all in
andropausal rats. In vitro studies indicate that the mechanism underlying these hormonal changes relies on inhibition of the pituitary tyrosine kinase and adrenocortical 3β-hydroxysteroid dehydrogenase enzymes by soy
isoflavones. Although the clinical studies are in their infancy, the opinion is that genistein and daidzein have
therapeutic potential for the safe treatment of ageing-caused androgen deprivation and glucocorticoid excess
with related metabolic/hemodynamic issues in males. Our accumulated experience and knowledge in the field of
biomedical effects of plant polyphenols have provided a platform for potential recommending the agenda to
organize and accelerate experimental research aimed at producing the optimal supplementation. We hypothesize
that an in vivo approach should first be exploited in the sequence of investigative steps, followed by in vitro
studies and synchronously conducted molecular docking analyses. In vivo research, besides establishing the
margin of exposure safety or adjustment of the correct polyphenol dose, enables identification and quantification
of the metabolites of applied polyphenols in the blood. Subsequent in vitro exploitation of the metabolites and
related docking analyses provide clarification of the molecular mechanisms of action of applied polyphenols.
Chemical modification of the polyphenol structure or coupling it with nanoparticles might be the next step in
optimizing the design of supplementation. Selected, intact or chemically-modified polyphenol molecules should
be included in preclinical studies on a more closely-related species, while clinical studies would finally assess the
safety and effectiveness of a polyphenol-based remedial strategy. The final supplement represents a product of an
appropriate technological process, conducted in accordance with the recommendations derived from the preceding research.
Ključne reči:
Andropause; Soy isoflavones; Corticosteroidogenesis; Potential research agenda; Supplementation designIzvor:
Medical Hypotheses, 2021, 148, 110516-Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200007 (Univerzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.1016/j.mehy.2021.110516
ISSN: 0306-9877
PubMed: 33548764