Concentration-dependent effect of silymarin on concanavalin A-stimulated mouse spleen cells in vitro

Abstract

Aims: Silymarin (SIL), a mixture of phenolic compounds, has a pleiotropic mode of action on various cell types, including immune cells. In this study, we investigated the concentration-dependent effect of SIL on proliferation of concanavalin A (CoA)-stimulated mouse spleen T lymphocytes, their viability, and secretion of IFN-g and IL-4 cytokines ex vivo in relation to gene expressions of transcription factors nuclear factor kappa B and Foxp3. In addition, metabolic activity of T cells was determined as changes in the mitochondrial membrane potential and apoptosis.Material/Methods: Isolated splenocytes were stimulated with lectin CoA and treated with SIL atthe concentrations of 5, 10, 20, and 40 μg/ml for 70 h and unstimulated cells served as the control. Cultures of splenocytes were evaluated for proliferation index following BrdU incorporation and viability of cells after trypan blue staining. Gene expressions of transcription factors and cytokines were assessed using real-time PCR, whereas ELISA test was applied to measure cytokine secretion. Mitochondrial membrane potential and apoptosis were determined by flow cytometry.Results: We demonstrated that CoA-activated mouse spleen T lymphocytes show different susceptibilities to low (£10 μg/ml) and higher (20 and 40 μg/ml) SIL concentrations. Low concentrations resulted in increased proliferation, cytokine secretion, and mitochondrial membrane potential and reduced transition of cells to apoptosis. High concentration of SIL had the opposite effect without exerting significant cytotoxicity and upregulated genes for cytokines and transcription factors on mRNA level. It is possible that individual subpopulations of T cells induced by CoA were differentially affected by the various SIL concentrations and the dose of 40 μg/ml had the profound suppressive effect. This correlated with the highest expression of Foxp3 factor, indicating that this dose stimulated preferential differentiation to Tregs lymphocytes.Conclusions: Treatment with suitable doses of SIL can provide potential benefits in the modulation of host immune functions in various diseases.

Therapeutic and prophylactic effect of flavonoids inpost‐COVID‐19 therapy

“…An essential function of flavonoids is the reduction of inflammatory markers, cytokine expression, modulation of transcription factors, and the effect on transduction signals. Silymarin inhibition of the NF‐κB pathway (Hrčková, Mačák Kubašková, Mudroňová, & Bardelčíková, 2020 ) has a potential therapeutic role in alleviating the severe form of COVID‐19. Ginkgetin, a biflavonoid from Ginkgo biloba, effectively decreased the expression of inflammation‐related protein prostaglandin E2 (PGE2), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and interleukin‐8 (IL‐8) (Q. Li et al, 2019 ).…”

Antiparasitic effects of selected isoflavones on flatworms

“…It has been demonstrated that there are strong direct scavengers of some free radicals ( Dehmlow et al ., 1996 ). It is well documented, that silymarin/silybin can decrease oxidative stress and has a protective effect on mitochondrial structure ( Rolo et al ., 2003 ) and immune cells function ( Hrčková et al ., 2020a ). There are also well documented antioxidant protective properties of silymarin/silybin in the prevention of toxic effects of various chemicals, such as arsenic, carbone tetrachloride, mycotoxins, thioacetamide, cisplatin, manganese, etc.…”