Ethanolic extract of Casearia sylvestris and its clerodane diterpen (caseargrewiin F) protect against DNA damage at low concentrations and cause DNA damage at high concentrations in mice's blood cells

Abstract

Casearia sylvestris is used in Brazil as a popular medicine to treat ulcer, inflammation and tumour. Caseargrewiin F is a clerodane diterpene isolated from the ethanolic leaf extract of C.sylvestris. The aim of the study was to assess the capacity of the ethanolic extract of C.sylvestris leaves and caseargrewiin F to protect DNA and verify if both the compounds cause some DNA damage, using the micronucleus (MN) test and comet assay in mice. Balb-C mice were treated with the extract [3.13, 6.25, 12.5, 25, 50 and 75 mg/kg body weight (b.w.)] and caseargrewiin F (0.16, 0.32, 0.63, 1.3, 2.5 and 3.8 mg/kg b.w.) for 14 days. On day 15, DNA damage was induced by intra-peritoneal (i.p.) injection of cyclophosphamide (CP) (i.p.) at 50 mg/kg b.w. after the MN test and comet assay were performed. A protective effect of ethanolic extract was observed in MN test (6.25 and 12.5 mg/kg b.w.) and the comet assay (3.13 and 6.25, 12.5 and 25 mg/kg b.w.). Caseargrewiin F showed protective effect at 0.63, 1.3 and 2.5 mg/kg b.w. only in comet assay. We also tested the ability of compounds of C.sylvestris to induce MN and to increase the comet assay tail moment. The experimental design was similar to the DNA protection assay except that in test groups we omitted the CP challenge. We observed increased damage at 50 and 75 mg/kg b.w. of ethanolic extract of C.sylvestris and caseargrewiin F at 3.18 mg/kg b.w. in both the MN test and comet assay. We conclude that ethanolic extract of C. sylvestris and caseargrewiin F can protect cells against DNA damage induced by CP at low concentrations, but at high concentrations these compounds also induce DNA damage.

Cardanol: toxicogenetic assessment and its effects when combined with cyclophosphamide

“…This was not expected, however, it is common to find similar results, as reported by Oliveira et al (2013) , who examined β-glucan activity, noting that this agent may be both genotoxic and antigenotoxic. In addition, similar data were reported for shiitake ( Lentinula edodes (Berkeley) Pegler; Miyaji et al , 2004 ) and Caesaria sylvestris extracts ( Oliveira et al , 2009b ).…”

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

“…Taken together, the data shown in the genotoxicity and antigenotoxicity assays are particularly interesting. They corroborate previous results obtained in animal models for compounds from C. sylvestris, where a weak genotoxic response and an antigenotoxic activity were observed concurrently in the comet assay at the same concentrations (de Oliveira et al, 2009). In addition, other studies described the same profile for compounds derived from natural products (Miyaji et al, 2004).…”

“…Additionally, the essential oil of the leaves was anticlastogenic when evaluated by observing chromosome aberrations in HTC cells (Sousa et al, 2007). Recently, a study using mouse blood cells showed that an ethanolic extract and caseargrewiin F protected DNA from damage in low concentrations and were genotoxic and mutagenic in high concentrations (de Oliveira et al, 2009).…”

Tropical biodiversity: has it been a potential source of secondary metabolites useful for medicinal chemistry?

“…The isolated compound caseargrewiin F (48) ( Figure 11) has been demonstrated to be both mutagenic and genotoxic at the highest dose; however, this same compound protects DNA against damage at low concentrations. 75 Further studies on 48 and casearin X (49) (Figure 11 ). This suggests that the cytotoxicity mechanism is probably related to a more specific pathway.…”

“…90 Kinetic studies aimed at elucidating the mechanism of cholinesterase inhibition elicited by this derivative have demonstrated noncompetitive cholinesterase inhibition as well central nervous selectivity with few peripheral side effects. 91 Taking these results into account, 70 and tacrine (74), a potent acetylcholinesterase inhibitor (AChEI), were selected for molecular hybridization (Figure 18), which furnished a range of isosteric pyridinic and pyrazinic compounds represented by ethyl 2- (75). These substances were assayed for their nematostatic and anthelmintic activities, since reversible and irreversible AChEIs have been employed in numerous applications including the control of parasites.…”