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Flavonolignans silybin, silychristin and 2,3-dehydrosilybin showed differential cytoprotective, antioxidant and anti-apoptotic effects on splenocytes from Balb/c mice

Year: 2025

Type: article

Abstract: Silymarin is an extract obtained from the seeds of milk thistle ( Sylibum marianum L., Asteraceae) and contains several structurally related flavonolignans and a small family of flavonoids. Mouse spleen cells represent highly sensitive primary cells suitable for studying the pharmacological potential and biofunctional properties of natural substances. Cultivation of splenocytes for 24 h under standard culture conditions (humidity, 37 °C, 5% CO 2 , atmospheric oxygen) resulted in decreased viability of splenocytes compared to intact cells. A cytoprotective effect of silybin (SB), silychristin (SCH) and 2,3-dehydrosilybin (DHSB) was observed at concentrations as low as 5 µmol/ml. At 50 µmol/ml, these substances restored and/or stimulated viability and mitochondrial membrane potential and had anti-apoptotic effect in the order SB > DHSB > SCH. The substances demonstrated a concentration-dependent activity in restoring the redox balance based on the changes in the concentration of reactive oxygen species (ROS), hydrogen peroxide (H 2 O 2 ) and nitric oxide. This was in the order DHSB > SCH > SB, which correlated with the suppressed expression of nuclear factor erythroid 2-related factor 2 (Nrf2), catalase and glutathione peroxidase. The strong stimulation of the superoxide dismutase 1 gene converting ROS to H 2 O 2 points to its dominant role in the maintaining redox homeostasis in splenocytes, which was disrupted by oxidative stress due to non-physiological culture conditions. Our study showed significant differences in the cytoprotective, antioxidant and anti-apoptotic activities of SB, SCH, and DHSB on splenocytes exposed to mild and AAPH-induced oxidative stress.

Source: Scientific Reports

DOI: 10.1038/s41598-025-89824-1

Authors: Zuzana Jurčacková, Gabriela Hrčková, Dagmar Mudroňová, Anna Alexovič Matiašová, David Biedermann