Silybin is considered to be the main biologically active component of silymarin. Its oxidized derivative 2,3-dehydrosilybin typically occurs in silymarin in small, but non-negligible amounts (up to 3%). Here, we investigated in detail complex biological activities of silybin and 2,3-dehydrosilybin optical isomers. Antioxidant activities of pure stereomers A and B of silybin and 2,3-dehydrosilybin, as well as their racemic mixtures, were investigated by using oxygen radical absorption capacity (ORAC) and cellular antioxidant activity (CAA) assay. All substances efficiently reduced nitric oxide production and cytokines (TNF-α, IL-6) release in a dose-dependent manner. Multidrug resistance (MDR) modulating potential was evaluated as inhibition of P-glycoprotein (P-gp) ATPase activity and regulation of ATP-binding cassette (ABC) protein expression. All the tested compounds showed strong dose-dependent inhibition of P-gp pump. Moreover, 2,3-dehydrosilybin A (30 µM) displayed the strongest sensitization of doxorubicin-resistant ovarian carcinoma. Despite these significant effects, silybin B was the only compound acting directly upon P-gp in vitro and also downregulating the expression of respective MDR genes. This compound altered the expression of P-glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2). 2,3-Dehydrosilybin AB exhibited the most effective inhibition of acetylcholinesterase activity. We can clearly postulate that silybin derivatives could serve well as modulators of a cancer drug-resistant phenotype.

• Keywords
• P-glycoprotein, acetylcholinesterase inhibition, cytokines, dehydrosilybin, doxorubicin resistance, expression profile, immunomodulation, silybin,
• Publication type
• Journal Article MeSH

Silybum marianum (L.) is a medicinal plant traditionally used in treatment of liver disorders. In last decades, silymarin (SM), a standardized extract from S. marianum seeds has been studied for its dermatological application, namely for UVB-protective properties. However, information on SM and its polyphenols effect on activity of enzymes participating in the (photo)aging process is limited. Therefore, evaluation of SM and its flavonolignans potential to inhibit collagenase, elastase, and hyaluronidase in tube tests was the goal of this study. The antioxidant and UV screening properties of SM and its flavonolignans silybin, isosilybin, silydianin, silychristin and 2,3-dehydrosilybin (DHSB) were also evaluated by a DPPH assay and spectrophotometrical measurement. DHSB showed the highest ability to scavenge DPPH radical and also revealed the highest UVA protection factor (PF-UVA) that corresponds with its absorption spectrum. SM and studied flavonolignans were found to exhibit anti-collagenase and anti-elastase activity. The most potent flavonolignan was DHSB. None of studied flavonolignans or SM showed anti-hyaluronidase activity. Our results suggest that SM and its flavonolignans may be useful agents for skin protection against the harmful effects of full-spectrum solar radiation including slowing down skin (photo)aging.

• Keywords
• Silybum marianum, collagenase, elastase, sun protection factor,
• MeSH
• Antioxidants chemistry   isolation & purification   MeSH
• Flavonolignans chemistry   isolation & purification   MeSH
• Skin drug effects   pathology   radiation effects   MeSH
• Humans MeSH
• Silybum marianum chemistry   MeSH
• Plant Extracts chemistry   MeSH
• Seeds chemistry   MeSH
• Silymarin chemistry   isolation & purification   MeSH
• Ultraviolet Rays adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants MeSH
• dehydrosilybin MeSH Browser
• Flavonolignans MeSH
• Plant Extracts MeSH
• Silymarin MeSH

• MeSH
• Animal Testing Alternatives methods   MeSH
• Cell Culture Techniques methods   MeSH
• Cell Line MeSH
• BALB 3T3 Cells MeSH
• Time Factors MeSH
• Dermatitis, Phototoxic * MeSH
• Keratinocytes radiation effects   MeSH
• Humans MeSH
• Mice MeSH
• Reproducibility of Results MeSH
• Toxicity Tests methods   MeSH
• Cell Survival radiation effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Letter 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.

• Keywords
• NF-κB, cytokines, fibroblasts, inflammation, skin wound healing,
• MeSH
• Anti-Inflammatory Agents pharmacology   MeSH
• Chemokines metabolism   MeSH
• Cytokines metabolism   MeSH
• Dermatitis drug therapy   genetics   metabolism   pathology   MeSH
• Gene Expression MeSH
• Fibroblasts drug effects   metabolism   MeSH
• Wound Healing drug effects   MeSH
• Humans MeSH
• Lipopolysaccharides immunology   MeSH
• RNA, Messenger genetics   metabolism   MeSH
• NF-kappa B metabolism   MeSH
• Cell Proliferation drug effects   MeSH
• Silymarin pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Inflammatory Agents MeSH
• Chemokines MeSH
• Cytokines MeSH
• Lipopolysaccharides MeSH
• RNA, Messenger MeSH
• NF-kappa B MeSH
• Silymarin MeSH