Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae)

Abstract

Studies have shown that Casearia sylvestris compounds protect DNA from damage both in vitro and in vivo. Complementarily, the aim of the present study was to assess the chemopreventive effect of casearin B (CASB) against DNA damage using the Ames test, the comet assay and the DCFDA antioxidant assay. The genotoxicity was assessed by the comet assay in HepG2 cells. CASB was genotoxic at concentrations higher than 0.30 μM when incubated with the FPG (formamidopyrimidine-DNA glycosylase) enzyme. For the antigenotoxicity comet assay, CASB protected the DNA from damage caused by H(2)O(2) in the HepG2 cell line in concentrations above 0.04 μM with post-treatment, and above 0.08 μM with pre-treatment. CASB was not mutagenic (Ames test) in TA 98 and TA 102. In the antimutagenicity assays, the compound was a strong inhibitor against aflatoxin B1 (AFB) in TA 98 (>88.8%), whereas it was moderate (42.7-59.4%) inhibitor against mytomicin C (MMC) in TA 102. Additionally, in the antioxidant assay using DCFDA, CASB reduced reactive oxygen species (ROS) generated by H(2)O(2). In conclusion, CASB was genotoxic to HepG2 cells at high concentrations; was protective of DNA at low concentrations, as shown by the Ames test and comet assay; and was also antioxidant.

Clerodane diterpenes: sources, structures, and biological activities

“…491 Finally, casearin X ( 1283 ) showed potent cytotoxic effects against CEM and HL-60 lines (IC 50 0.4 μM) and PBMC cells (IC 50 1.2 μM) and caused cell death via apoptotic pathways. These data further substantiated the promising antitumor-related properties of casearins.…”

Efficacy of botanical extracts from Brazilian savannah against Diabrotica speciosa and associated bacteria

“…Antibacterial, antileishmanial, and anti-inflammatory activities were also reported for b¢-chalcanone (Hermoso et al 2003;Nowakowska 2007). Clerodane diterpene from C. sylvestris has shown cytotoxic, anti-fungal, and anti-parasitic activities (Prieto et al 2013;Bou et al 2014).…”

Counteracting effects on free radicals and histological alterations induced by a fraction with casearins

“…Thus, the evaluation of the antioxidant activity of natural products such as casearins becomes especially important in tissue and organs more vulnerable to oxidative stress, like the brain (Barbosa et al 2006, Pala andGurkan 2008). In relation to C. sylvestris compounds, these analyses are also critical since they have chemotherapeutic potential (Ferreira et al 2010, Ferreira et al 2011, Prieto et al 2013, Ferreira et al 2014) and many cancer patients fail chemotherapy because of undesired side effects, in which liver and brain tissues are frequently targets of oxidative stress and chemotherapeutic toxicity (Williams et al 2002). Then, in vivo studies were also performed to visualize protection by the FC against generation of free radicals in complex systems.…”