title: Verminoside- and verbascoside-induced genotoxicity on human lymphocytes: involvement of PARP-1 and p53 proteins.
abstract: Verminoside and verbascoside are natural compounds present in plants used in traditional medicine. They exhibit several biological activities including anti-inflammatory, anti-bacterial and anti-tumor properties. The potential applications of these compounds as ingredients in pharmaceutical formulations and cosmetics prompted us to investigate on cytotoxic and genotoxic activity of verminoside and verbascoside on human lymphocytes using genetic toxicity assays recommended in preclinical studies by the US Food and Drug Administration (FDA). We analyzed chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) as well as the mitotic index (MI) and cell viability after the treatments with verminoside and verbascoside. This report is the first to clearly demonstrate a significant increase of structural CAs and SCEs on normal human lymphocytes associated with a reduction of the MI in both verminoside- and verbascoside-treated cells. Moreover, we observed enhanced protein expression levels of PARP-1 and p53 that are key regulatory proteins involved in cell proliferation and DNA repair. Interestingly, mass spectrometric analysis of the compounds in the culture supernatants also showed that verminoside remained unchanged during the culture period while verbascoside was hydrolyzed to its derivative, caffeic acid and the last one seems to be responsible for the observed biological activity.
authors.affiliation: Department of Pharmaceutical Sciences, University of Salerno, Via Ponte don Melillo, 84084 Fisciano, Salerno, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Santoro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianco
authors.forename: Patrizia
authors.initials: P
authors.lastname: Picerno
authors.forename: Rita Patrizia
authors.initials: RP
authors.lastname: Aquino
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Autore
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzocco
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gazzerro
authors.forename: Maria Brigida
authors.initials: MB
authors.lastname: Lioi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bifulco
mesh_terms: D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000633:toxicity*; D006801:Humans; D039823:Iridoids / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D009153:Mutagens; D010636:Phenols / Q000633:toxicity*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D059808:Polyphenols
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D039823:Iridoids; D009153:Mutagens; D010636:Phenols; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D016159:Tumor Suppressor Protein p53; C506490:verminoside; C058956:acteoside; D059808:Polyphenols; C499320:PARP1 protein, human