2,3-Dehydrosilybin A/B as a pro-longevity and anti-aggregation compound

Filippopoulou, Konstantina; Papaevgeniou, Nikoletta; Lefaki, Maria; Paraskevopoulou, Anna; Biedermann, David; Křen, Vladimı́r; Chondrogianni, Niki

doi:10.1016/j.freeradbiomed.2016.12.042

Cited by 33 publications

(34 citation statements)

References 70 publications

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“…2,3-Dehydrosilybin and its gallates were also more efficient inhibitors of angiogenesis that silybin and silybin derived gallates [12,13]. In a more complex model, 2,3-dehydrosilybin (and especially the A enantiomer) displayed lifespan-extension effect superior to that of silybin, isosilybin, silychristin and silydianin in Caenorhabditis elegans [14]. Moreover, 2,3-dehydrosilybin inhibited basal cell carcinoma allograft tumor growth more than silybin in mice [15].…”

Section: Resultsmentioning

confidence: 95%

2,3-Dehydroderivatives of Silymarin Flavonolignans: Prospective Natural Compounds for the Prevention of Chronic Diseases

Valentová

Biedermann

Křen

2019

CA16112 - Luxemburg 2019

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Silybum marianum fruit extract silymarin displays various biological activities, which are attributed mostly to its major component silybin. However, silymarin contain several other isomeric flavonolignans (isosilybin, silychristin, silydianin) and their oxidation products, the 2,3-dehydroflavonolignans (2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3-dehydrosilydianin). The latter compounds were found to be 1-2 orders of magnitude more efficient radical scavengers, reducing, chelating, cytoprotective, anti-aging, anti-cancer and anti-angiogenic agents than the parent flavonolignans. Although 2,3-dehydroflavonolignans occur in silymarin as minorities, they seem to be responsible for the majority of the biological activity and therefore have potential for the prevention of chronic diseases.

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Section: Resultsmentioning

confidence: 95%

2,3-Dehydroderivatives of Silymarin Flavonolignans: Prospective Natural Compounds for the Prevention of Chronic Diseases

Valentová

Biedermann

Křen

2019

CA16112 - Luxemburg 2019

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“…Silybin, a major active constituent of silymarin (extract of the milk thistle seeds), has been shown to have antioxidant and cytoprotective as well as antitumor effects. Moreover, several studies performed in C. elgans suggest that silybin may display antiaging activity, mainly based on counteracting age-related loss of proteostasis [ 172 – 174 ]. In analogy with other flavonoids, also in this case, the antioxidant and cytoprotective effects seem to be related to the activation of Nrf2 pathway [ 175 ].…”

Section: Nrf2-activating Phytochemicals: Senescence Inducers Senomentioning

confidence: 99%

Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy

Malavolta

Bracci

Santarelli

et al. 2018

Mediators of Inflammation

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The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms) that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity.

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“…The reason is because 2,3-dehydrosilybin A has been revealed to be more effective than its enantiomer, 2,3-dehydrosilybin B, in extending lifespan and preventing Aβ aggregation in cell and whole organism models. 18 The syntheses of 20- O -alkyl-2,3-dehydrosilybins ( 14–20 ) and 5,20- O -dialkyl-2,3-dehdyrosilybins ( 21–27 ) were accomplished following the procedures as illustrated in Scheme 1, which were designed by taking advantage of (i) the reactivity of the phenolic hydroxyl groups at different positions in silybin toward etherification is 7-OH > 20-OH > 5-OH; 6 (ii) aerobic oxidation of silybin to 2,3-dehydrosilybin only can be achieved in the simultaneous presence of base (e.g. potassium carbonate and potassium acetate) and air; 6,14 (iii) the 3-OH becomes the most active functional group toward etherification once silybin is oxidized to the 2,3-dehydrosilybin, 6,14,19 which has been rationalized by the electrochemistry measurements and bond dissociation energy calculations, 20 and (iv) the 3-OH in 7-0-benzylsilybin is much easier to be aerobically oxidized than that in silybin, which we noticed from our recent experiments.…”

Section: Resultsmentioning

confidence: 99%

5- or/and 20-O-alkyl-2,3-dehydrosilybins: Synthesis and biological profiles on prostate cancer cell models

Vue

Zhang

Lee

et al. 2017

Bioorganic & Medicinal Chemistry

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To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O-alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially available silybin, have been successfully developed. The first three reactions in the syntheses were completed through a one-pot procedure by managing anaerobic and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3-dehydrosilybins, including seven 20-O-alkyl, seven 5,20-O-dialkyl, and seven 5-O-alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their biological profiles. Our WST-1 cell proliferation assay data indicate that nineteen out of the twenty-one 2,3-dehydrosilybins possess significantly improved antiproliferative potency as compared with silybin toward both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145). 5-O-Alkyl-2,3-dehydrosilybins were identified as the optimal subgroup that can consistently inhibit cell proliferation in three prostate cancer cell models with all IC50 values lower than 8 μM. Our flow cytometry-based assays also demonstrate that 5-O-heptyl-2,3-dehydrosilybin effectively arrests the cell cycle in the G0/G1 phase and activates PC-3 cell apoptosis.

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2,3-Dehydrosilybin A/B as a pro-longevity and anti-aggregation compound

Cited by 33 publications

References 70 publications

2,3-Dehydroderivatives of Silymarin Flavonolignans: Prospective Natural Compounds for the Prevention of Chronic Diseases

2,3-Dehydroderivatives of Silymarin Flavonolignans: Prospective Natural Compounds for the Prevention of Chronic Diseases

Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy

5- or/and 20-O-alkyl-2,3-dehydrosilybins: Synthesis and biological profiles on prostate cancer cell models

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