Modulatory effect of pomegranate peel extract on key regulators of ovarian cellular processes in vitro.

In this study, response of ovarian cells (human granulosa cell line HGL5, and human adenocarcinoma cell line OVCAR-3) to short-term pomegranate peel extract (PPE) treatment (for 24 hours in cell culture) was evaluated in vitro. Quantitative and qualitative screening of polyphenols revealed punicalagins α and ß as major polyphenolic components. Total phenolic content (TPC) was 93.76 mg GAE/g d.w. with a high antioxidant activity of 95.30 mg TEAC/g d.w. In OVCAR-3, PPE treatment inhibited the metabolic activity, and increased cyclin-dependent kinase 1 (CDKN1A, p21) level at the highest dose, but not in HGL5. Flow cytometry analysis could not detect any significant difference between proportions of live, dead, and apoptotic cells in both cell lines. Reactive oxygen species (ROS) revealed an antioxidant effect on HGL5, and a prooxidant effect by stimulating ROS generation in OVCAR-3 cells at the higher doses of PPE. However, in contrast to HGL5, PPE treatment decreased release of growth factors - TGF-ß2 and EGF at the highest dose, as well as their receptors TGFBR2 and EGFR in OVCAR-3 cells. PPE also influenced steroidogenesis in granulosa cells HGL5 by stimulating 17ß-estradiol secretion at higher doses. In conclusion, the present study highlighted the bioactive compounds in pomegranate peels and the possible mechanisms of action of PPE, shedding light on its promising role in ovarian cancer (chemo)prevention and/or management.

The multiple actions of grape and its polyphenols on female reproductive processes with an emphasis on cell signalling.

Grapes are an economically important fruit crop, and their polyphenols (mainly phenolic acids, flavanols, flavonols, anthocyanins, proanthocyanidins, and stilbenes) can exert a wide range of health benefits as an interesting and valuable dietary supplement for natural complementary therapy. However, their potential physiological and therapeutic actions on reproductive processes have not been sufficiently elucidated. This evidence-based study presents current knowledge of grape extracts and polyphenols, as well as their properties and therapeutical actions in relation to female reproduction in a nutshell. Grape extract, and its polyphenols such as resveratrol, proanthocyanidin B2 or delphinidin may influence female reproductive physiology and pathology, as well as regulate multiple signaling pathways related to reproductive hormones, steroid hormones receptors, intracellular regulators of oxidative stress and subsequent inflammation, apoptosis, and proliferation. Their role in the management of ovarian cancer, age-related reproductive insufficiency, ovarian ischemia, PCOS, or menopausal syndrome has been indicated. In particular, the potential involvement of grapeseed extracts and/or proanthocyanidin B2 and delphinidin on ovarian steroidogenesis, oocyte maturation, and developmental capacity has been implicated, albeit at different regulatory levels. Grape polyphenols exert a wide range of health benefits posing grape extract as an interesting and valuable dietary supplement for natural complementary therapy. This evidence-based study focuses on the actions of grapeseed extract and grape polyphenols on female reproductive processes at various regulatory levels and multiple signalling pathways by regulating reproductive hormones (GnRH, gonadotropins, prolactin, steroid hormones, IGFBP), steroid receptors, markers of proliferation and apoptosis. However, lack of knowledge of standardized dosages so far limits their clinical application despite the wide range of their biological and therapeutic potentials.

The Multiple Actions of Amygdalin on Cellular Processes with an Emphasis on Female Reproduction.

The present review summarizes the current knowledge on the provenance and properties, metabolism and toxicity, mechanism of action, physiological, and therapeutic roles of amygdalin-a molecule present in the seeds of apricot and other plants-with an emphasis on the action of amygdalin on reproductive processes, particularly in the female. Amygdalin influences physiological processes including female reproduction at various regulatory levels via extra- and intracellular signaling pathways regulating secretory activity, cell viability, steroidogenesis, proliferation, and apoptosis. On the other hand, while being metabolized in the body, amygdalin releases significant amounts of cyanide, which may lead to acute health hazard in those individuals who may be at risk. Despite some contradictions in the available data about benefits and toxic effects of amygdalin, its potential applicability at low doses may present a promising tool for regulation of various reproductive and other physiological processes including disease management primarily in cancer phytotherapy, animal production, medicine, and biotechnology. However, further research involving carefully designed dose-response studies is required to overcome the possible side effects of amygdalin and assure its safety as a therapeutic agent.

Enhancing Bioavailability of Nutraceutically Used Resveratrol and Other Stilbenoids.

Stilbenoids are interesting natural compounds with pleiotropic in vitro and in vivo activity. Their well-documented biological properties include anti-inflammatory effects, anticancer effects, effects on longevity, and many others. Therefore, they are nowadays commonly found in foods and dietary supplements, and used as a part of treatment strategy in various types of diseases. Bioactivity of stilbenoids strongly depends on different types of factors such as dosage, food composition, and synergistic effects with other plant secondary metabolites such as polyphenols or vitamins. In this review, we summarize the existing in vitro, in vivo, and clinical data from published studies addressing the optimization of bioavailability of stilbenoids. Stilbenoids face low bioavailability due to their chemical structure. This can be improved by the use of novel drug delivery systems or enhancers, which are discussed in this review. Current in vitro and in vivo evidence suggests that both approaches are very promising and increase the absorption of the original substance by several times. However, data from more clinical trials are required.