verminoside and acteoside

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.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Blotting, Western; Cell Line; Cell Survival; Chromosome Aberrations; Chromosomes; DNA Repair; Dose-Response Relationship, Drug; Glucosides; Humans; Iridoids; Lymphocytes; Male; Mitotic Index; Mutagens; Phenols; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Sister Chromatid Exchange; Spectrometry, Mass, Electrospray Ionization; Tumor Suppressor Protein p53

Kigelia africana is a plant used in Africa for anti-inflammatory, anti-microbial, and anti-skin-aging effects. Various papers have reported on the composition and biological activities of its CH2Cl2 extracts and dermal formulations. Chemical analysis of a polar extract of fruit from K. africana indicated the presence of verminoside (1), an iridoid, as a major constituent, and of a series of polyphenols such as verbascoside (2). In vitro assays showed that 1 had significant anti-inflammatory effects, inhibiting both iNOS expression and NO release in the LPS-induced J774.A1 macrophage cell line. Cytotoxicity and cutaneous irritation of the extract and of compounds 1 and 2 were investigated. The crude extract and 1 did not affect cell viability in vitro either in cells grown in monolayers (ML) or in the reconstituted human epidermis (RHE, 3D) model; neither caused release of pro-inflammatory mediators or histomorphological modification of RHE.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bignoniaceae; Cells, Cultured; Epidermis; Fruit; Glucosides; Humans; Iridoids; Macrophages; Mali; Mice; Models, Biological; Molecular Structure; Monocytes; Nitric Oxide; Nitric Oxide Synthase Type II; Phenols; Plants, Medicinal