Modulation of Skin Inflammatory Response by Active Components of Silymarin.

Jana Juráňová,Catherine Baugé,Karim Boumediene,Jitka Ulrichová,Jana Franková,Juliette Aury-Landas,David Biedermann

doi:10.3390/molecules24010123

Abstract

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.

Highlights

Skin wound healing is a highly organized process of tissue regeneration that requires the interplay of skin resident cells, e.g., keratinocytes and fibroblasts, and recruited leukocyte subtypes participating in three sequential but overlapping phases: Inflammation, proliferation, and maturation [1]
The transition from the inflammatory to proliferative phase is an essential step during wound healing and the optimization of inflammation is targeted by current treatments
The sensing of microbial infection by transmembrane proteins such as toll-like receptors (TLRs) triggers intracellular pro-inflammatory pathways, including the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinases (MAPK) pathways resulting in the expression of pro-inflammatory cytokines e.g., interleukin-1 (IL-1) family of cytokines or interleukin-6 (IL-6), chemokines (IL-8) and enzymes such as cyclooxygenase-2 (COX-2) [2,3,4]

Summary

Introduction

Skin wound healing is a highly organized process of tissue regeneration that requires the interplay of skin resident cells, e.g., keratinocytes and fibroblasts, and recruited leukocyte subtypes participating in three sequential but overlapping phases: Inflammation, proliferation, and maturation [1]. The sensing of microbial infection by transmembrane proteins such as toll-like receptors (TLRs) triggers intracellular pro-inflammatory pathways, including the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinases (MAPK) pathways resulting in the expression of pro-inflammatory cytokines e.g., interleukin-1 (IL-1) family of cytokines or interleukin-6 (IL-6), chemokines (IL-8) and enzymes such as cyclooxygenase-2 (COX-2) [2,3,4]. These soluble mediators organize the inflammatory response by attracting neutrophils. The dysregulated excessive or persistent production of these inflammatory mediators generates a sustained pro-inflammatory state, resulting in tissue damage [3,4]

Methods

Results

Discussion

Conclusion