E-Stilbenes: General Chemical and Biological Aspects, Potential Pharmacological Activity Based on the Nrf2 Pathway.

Stilbenes are phytoalexins, and their biosynthesis can occur through a natural route (shikimate precursor) or an alternative route (in microorganism cultures). The latter is a metabolic engineering strategy to enhance production due to stilbenes recognized pharmacological and medicinal potential. It is believed that in the human body, these potential activities can be modulated by the regulation of the nuclear factor erythroid derived 2 (Nrf2), which increases the expression of antioxidant enzymes. Given this, our review aims to critically analyze evidence regarding E-stilbenes in human metabolism and the Nrf2 activation pathway, with an emphasis on inflammatory and oxidative stress aspects related to the pathophysiology of chronic and metabolic diseases. In this comprehensive literature review, it can be observed that despite the broad number of stilbenes, those most frequently explored in clinical trials and preclinical studies (in vitro and in vivo) were resveratrol, piceatannol, pterostilbene, polydatin, stilbestrol, and pinosylvin. In some cases, depending on the dose/concentration and chemical nature of the stilbene, it was possible to identify activation of the Nrf2 pathway. Furthermore, the use of some experimental models presented a challenge in comparing results. In view of the above, it can be suggested that E-stilbenes have a relationship with the Nrf2 pathway, whether directly or indirectly, through different biological pathways, and in different diseases or conditions that are mainly related to inflammation and oxidative stress.

The role played by oral antioxidant therapies in preventing and treating preeclampsia: An updated meta-analysis.

AIMS: Performing an up-to-date meta-analysis of oral antioxidant therapies and determining whether they are effective in preventing and/or treating preeclampsia (PE). DATA SYNTHESIS: Search was performed in PubMed, CENTRAL, LILACS, Web of Science, and ScienceDirect databases. The risk of bias was assessed based on using Cochrane Collaboration's tool. A funnel plot was created, and Egger's and Peter's test was carried out to assess publication bias in the primary outcome of prevention studies. The overall quality of the evidence was assessed based on using the Grading of Recommendations Assessment, Developing and Evaluation (GRADE) tool; a formal protocol was published in the PROSPERO database (registration number CRD42022348992). In total, 32 studies were taken into consideration for analysis purposes; 22 studies focused on investigating preeclampsia prevention methods, whereas 10 focused on its treatment. Significant results associated with the incidence of preeclampsia were observed in prevention studies comprising 11,198 subjects and 1106 events in the control groups, as well as 11,156 subjects and 1048 events in the intervention groups (relative risk [RR]: 0.86, 95% confidence interval [CI]: [0.75, 0.99], P = 0.03; I2 = 44%, P = 0.02). With respect to outcomes associated with treatment studies, only intrauterine growth restriction has shown significant effects. Egger's and Peter's test has evidenced publication bias. Six outcomes in prevention studies were classified as having low quality and two as having moderate quality, whereas all three outcomes assessed in treatment studies were classified as having moderate quality. CONCLUSIONS: Antioxidant therapy has shown beneficial effects on preeclampsia prevention; moreover, the positive impact of this therapy on intrauterine growth restriction was observed during the disease treatment.

Hyperferritinemia worsens the perinatal outcomes of conceptions of pregnancies with preeclampsia.

BACKGROUND AND AIMS: To analyze the prevalence of hyperferritinemia in pregnant women with preeclampsia and its association with adverse perinatal outcomes. METHODS: A cross-sectional study carried out in 2017 with a convenience sample of pregnant women with preeclampsia attended at a high-risk maternity hospital in Alagoas, Brazil. Socioeconomic, lifestyle, clinical and biochemical data were collected through a structured questionnaire. Type of delivery, gestational age, weight and length at birth, and Apgar score were analyzed as outcome variables. Women were dichotomized according to the serum ferritin level (150 ng/mL). Poisson regression models were used to analyze the effect of hyperferritinemia on the outcome variables. Estimates were presented as prevalence ratio with 95% confidence intervals (PR [95% CI]). RESULTS: Based on the Fisher's exact statistical teste and in the proportions of the neonatal outcome (birth weight), with a statistical significance of 5%, the statistical power of the sample studied was 83%. Two hundred six pregnant women with preeclampsia were recruited, which 8.74% presented hyperferritinemia. Except for ferritin level, there were no differences in C-reactive protein (CRP), hemoglobin, Glutamate Oxaloacetate Transaminase (GOT) and Pyruvic Glutamic Transaminase (PGT) levels between women with or without hyperferritinemia. After adjusting for potential confounders, hyperferritinemia was associated with low birth weight (2.19 [2.13-3.89 95%CI]), low birth length (7.76 [2.52-23.8 95% CI]) and being born small for gestational age (3.14 [1.36-7.28 95% CI]). CONCLUSION: In the presence of hyperferritinemia, preeclampsia patients were associated with a higher rate of unfavorable neonatal outcomes.