title: 2,3-Dehydrosilybin A/B as a pro-longevity and anti-aggregation compound.
abstract: Aging is an unavoidable process characterized by gradual failure of homeostasis that constitutes a critical risk factor for several age-related disorders. It has been unveiled that manipulation of various key pathways may decelerate the aging progression and the triggering of age-related diseases. As a consequence, the identification of compounds, preferably natural-occurring, administered through diet, with lifespan-extending, anti-aggregation and anti-oxidation properties that in parallel exhibit negligible side-effects is the main goal in the battle against aging. Here we analyze the role of 2,3-dehydrosilybin A/B (DHS A/B), a minor component of silymarin used in a plethora of dietary supplements. This flavonolignan is well-known for its anti-oxidative and neuroprotective properties, among others. We demonstrate that DHS A/B confers oxidative stress resistance not only in human primary cells but also in the context of a multi-cellular aging model, namely Caenorhabditis elegans (C. elegans) where it also promotes lifespan extension. We reveal that these DHS A/B outcomes are FGT-1 and DAF-16 dependent. We additionally demonstrate the anti-aggregation properties of DHS A/B in human cells of nervous origin but also in nematode models of Alzheimer's disease (AD), eventually leading to decelerated progression of AD phenotype. Our results identify DHS A/B as the active component of silymarin extract and propose DHS A/B as a candidate anti-aging and anti-aggregation compound.
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., Athens 11635, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Filippopoulou
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., Athens 11635, Greece; Institute of Nutrition, Faculty of Biology and Pharmacy, Friedrich Schiller University of Jena, 25 Dornburger Str., 07743 Jena , Germany.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Papaevgeniou
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., Athens 11635, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Lefaki
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., Athens 11635, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Paraskevopoulou
authors.affiliation: Institute of Microbiology, Laboratory of Biotransformation, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Biedermann
authors.affiliation: Institute of Microbiology, Laboratory of Biotransformation, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Křen
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., Athens 11635, Greece. Electronic address: nikichon@eie.gr.
authors.forename: Niki
authors.initials: N
authors.lastname: Chondrogianni
mesh_terms: D000818:Animals; D016466:CHO Cells; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000187:drug effects*; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology*; D066263:Protein Aggregation, Pathological / Q000517:prevention & control*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C585488:FGT-1 protein, C elegans; D051246:Glucose Transport Proteins, Facilitative; D020011:Protective Agents; D012838:Silymarin; D000077385:Silybin
keywords: 2,3-dehydrosilybin A/B; Anti-aggregation; Anti-aging; Anti-oxidation; DAF-16; FGT-1