Silibinin Modulates NF-κB Activation and Heat Shock Protein in Preeclampsia-Like Rat Model

Abstract

Problem

Preeclampsia (PE) is a serious human pregnancy complication and remains the most complex hypertensive disorder due to its multifactorial nature and multisystemic effects. Despite the incomplete understanding of the PE pathophysiology, it is well-accepted that placental changes in PE are associated with oxidative stress, increasing the excessive production of cytokines and other inflammatory mediators. Thus, agents such as silibinin, a non-toxic natural polyphenolic flavonoid with antioxidant, anti-inflammatory, and hepatoprotective properties could modulate this profile for better disease resolution. This study aimed to investigate the effect of silibinin treatment on Nω-nitro-L-arginine methyl ester (L-NAME)-induced PE in rats, exploring its potential as a preventive anti-inflammatory agent.

Methods of Study

Pregnant Wistar rats were treated or not during gestation (days 10–19) with L-NAME (70–80 mg/kg/day) in drinking water and with silibinin (100 mg/kg/day, orally) starting on days 0, 7 or 14 of pregnancy. Systolic blood pressure was recorded on gestation days 0 and 20. The rats were euthanized on day 20. Then, we evaluated proteinuria, maternal weight gain, and litter weight. Tumor necrosis factor- alpha (TNF-α), interleukin-1 (IL-1β), IL-6, IL-10, interferon-gamma (IFN-γ), heat shock protein 70 (Hsp70) and NF-κB activity were determined in liver and placenta homogenates.

Results

Our findings indicated that silibinin treatment decreased the production of the inflammatory cytokines TNF-α, IL-1β, IFN-γ, and reduced Hsp70 levels in the placenta and liver homogenate. NF-κB activation was also decreased in these organs of silibinin-treated groups, especially in the LN+SB0 and LN+SB7 groups.

Conclusion

This study introduces a novel use of silibinin as a preventive agent in a PE-like model that reproduces essential features of human PE, providing physiological relevance to the findings. Overall, our data emphasize the translational potential of silibinin for PE prevention, showing promising effects on key inflammatory and stress-related pathways.