Silibinin treatment reduces inflammatory cytokines and `NF-κB` activation in preeclampsia-like rat model

Preeclampsia (PE) is a severe, multifactorial hypertensive disorder of human pregnancy, characterized by multisystemic effects and an incomplete understanding of its pathophysiology. A key aspect of PE involves placental changes linked to oxidative stress and an excessive production of cytokines and other inflammatory mediators. Current treatments often manage symptoms rather than addressing the underlying inflammatory drivers. Silibinin, a natural polyphenolic flavonoid, possesses known antioxidant, anti-inflammatory, and hepatoprotective properties, making it a promising candidate to modulate this inflammatory profile and potentially offer a preventive strategy for PE.

Pregnant Wistar rats were used to establish a preeclampsia-like model by administering Nω-nitro-L-arginine methyl ester (L-NAME) at 70-80 mg/kg/day in drinking water from gestation days 10-19. Concurrently, some groups received silibinin (100 mg/kg/day, orally), initiated on gestation days 0, 7, or 14. Systolic blood pressure was monitored on days 0 and 20, with euthanasia occurring on day 20. Primary endpoints included proteinuria, maternal weight gain, and litter weight. Inflammatory markers such as TNF-α, IL-1β, IL-6, IL-10, IFN-γ, Hsp70, and NF-κB activity were quantified in liver and placenta homogenates using unspecified assays.

Silibinin treatment significantly modulated the inflammatory profile in the preeclampsia-like rat model. The intervention led to a notable decrease in the production of key pro-inflammatory cytokines, specifically TNF-α, IL-1β, and IFN-γ, within both placental and liver homogenates. Furthermore, levels of Hsp70, a stress-response protein often elevated in inflammatory conditions, were also reduced in these organs. A critical finding was the observed reduction in NF-κB activation, a central regulator of inflammatory gene expression, across the silibinin-treated groups. This effect was particularly pronounced in the groups where silibinin administration began early in pregnancy (LN+SB0 and LN+SB7 groups), suggesting a time-dependent efficacy. While specific quantitative data (e.g., percentages, p-values) were not provided in the abstract, the consistent reduction across multiple inflammatory markers underscores silibinin's broad anti-inflammatory impact. The study's conclusion highlights these modulatory effects as physiologically relevant, reproducing essential features of human PE.

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, with NF-κB activation also decreased.