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.

• Klíčová slova
• P-glycoprotein, acetylcholinesterase inhibition, cytokines, dehydrosilybin, doxorubicin resistance, expression profile, immunomodulation, silybin,
• Publikační typ
• časopisecké články 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.

• Klíčová slova
• Silybum marianum, collagenase, elastase, sun protection factor,
• MeSH
• antioxidancia chemie   izolace a purifikace   MeSH
• flavonolignany chemie   izolace a purifikace   MeSH
• kůže účinky léků   patologie   účinky záření   MeSH
• lidé MeSH
• ostropestřec mariánský chemie   MeSH
• rostlinné extrakty chemie   MeSH
• semena rostlinná chemie   MeSH
• silymarin chemie   izolace a purifikace   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• dehydrosilybin MeSH Prohlížeč
• flavonolignany MeSH
• rostlinné extrakty MeSH
• silymarin MeSH

• MeSH
• alternativy testů na zvířatech metody   MeSH
• buněčné kultury metody   MeSH
• buněčné linie MeSH
• buňky BALB 3T3 MeSH
• časové faktory MeSH
• fototoxická dermatitida * MeSH
• keratinocyty účinky záření   MeSH
• lidé MeSH
• myši MeSH
• reprodukovatelnost výsledků MeSH
• testy toxicity metody   MeSH
• viabilita buněk účinky záření   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• dopisy 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.

• Klíčová slova
• NF-κB, cytokines, fibroblasts, inflammation, skin wound healing,
• 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
• Názvy látek
• antiflogistika MeSH
• chemokiny MeSH
• cytokiny MeSH
• lipopolysacharidy MeSH
• messenger RNA MeSH
• NF-kappa B MeSH
• silymarin MeSH