Silymarin is a flavonoid complex isolated from the plant Silybum marianum which is well known for its antioxidant, hepatoprotective and immunomodulatory effects. Since little is known about its anti-inflammatory properties and healing effects, our study focused on whether or not silymarin components reduce inflammation and support epidermis regeneration. Lipopolysaccharides (LPS) and sodium dodecyl sulfate (SDS) were used to induce inflammation in normal human epidermal keratinocytes (NHEKs) and reconstructed epidermis (RHE), respectively. The expression of pro-inflammatory cytokines (IL-1, IL-6 and IL-8) in NHEKs and RHE was measured by enzyme - linked immunosorbent assay (ELISA). The expression of cytokeratin 14 and loricrin in RHE was detected by immunofluorescent analysis. Hematoxylin and eosin staining was used for the morphological evaluation of RHE. It was determined that 2, 3 - dehydrosilybin (DHSB) downregulated the production of selected pro-inflammatory cytokines produced by NHEKs. Although all layers of RHE displayed full thickness, when SDS was applied, cell detachment was seen in the stratum corneum and loricrin expression was diminished.
- MeSH
- antiflogistika farmakologie MeSH
- cytokiny metabolismus MeSH
- dodecylsíran sodný toxicita MeSH
- epidermis účinky léků metabolismus MeSH
- keratin-14 metabolismus MeSH
- keratinocyty účinky léků metabolismus MeSH
- lidé MeSH
- lipopolysacharidy toxicita MeSH
- membránové proteiny metabolismus MeSH
- quercetin farmakologie MeSH
- silymarin farmakologie MeSH
- zánět chemicky indukované MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In this study, we compared selected silymarin components, such as quercetin (QE), 2,3-dehydrosilybin (DHS) and silybin (SB), with the anti-inflammatory drug indomethacin (IND) in terms of their wound healing potential. In view of the fact that pathological cutaneous wound healing is associated with persistent inflammation, we studied their anti-inflammatory activity against inflammation induced by bacterial lipopolysaccharide (LPS). We investigated the regulation of crucial pro-inflammatory transcription factors-nuclear factor kappa-B (NF-κB) and activator protein 1 (AP-1)-as well as the expression of downstream inflammatory targets by Western blotting, real-time PCR (RT-PCR), electrophoretic mobility shift assay (EMSA), and/or enzyme-linked immunosorbent assay (ELISA) in vitro using primary normal human dermal fibroblasts (NHDF). We demonstrated the greater ability of DHS to modulate the pro-inflammatory cytokines production via the NF-κB and AP-1 signaling pathways when compared to other tested substances. The prolonged exposure of LPS-challenged human dermal fibroblasts to DHS had both beneficial and detrimental consequences. DHS diminished interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion but induced the significant upregulation of IL-8 mRNA associated with NF-κB and AP-1 activation. The observed conflicting results may compromise the main expected benefit, which is the acceleration of the healing of the wound via a diminished inflammation.
- MeSH
- antiflogistika farmakologie MeSH
- chemokiny metabolismus MeSH
- cytokiny metabolismus MeSH
- dermatitida farmakoterapie genetika metabolismus patologie MeSH
- exprese genu MeSH
- fibroblasty účinky léků metabolismus MeSH
- hojení ran účinky léků MeSH
- lidé MeSH
- lipopolysacharidy imunologie MeSH
- messenger RNA genetika metabolismus MeSH
- NF-kappa B metabolismus MeSH
- proliferace buněk účinky léků MeSH
- silymarin farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH