Abstract
Silymarin (SM), a standardized extract derived from Silybum marianum (L.) Gaertn, is primarily composed of flavonolignans, with silibinin (SB) as its major active constituent. The present study aimed to evaluate the antigenotoxic activities of SM and SB using the alkaline comet assay in whole blood cells and to assess their effects on the expression of genes associated with carcinogenesis and chemopreventive processes. Different concentrations of SM or SB (1.0, 2.5, 5.0, and 7.5 mg/ml) were used in combination with the DNA damage-inducing agent methyl methanesulfonate (MMS, 800 μM) to evaluate their genoprotective potential. To investigate the role of SM and SB in modulating gene expression, we performed quantitative real-time PCR (qRT-PCR) analysis of five genes that are known to be involved in DNA damage, carcinogenesis, and/or chemopreventive mechanisms. Treatment with SM or SB was found to significantly reduce the genotoxicity of MMS, upregulate the expression of PTEN and BCL2, and downregulate the expression of BAX and ABL1. We observed no significant changes in ETV6 expression levels following treatment with SM or SB. In conclusion, both SM and SB exerted antigenotoxic activities and modulated the expression of genes related to cell protection against DNA damage.
Highlights
According to the World Health Organization, 70% to 95% of the world’s population rely on traditional medicine for primary health care, and most health practices involve the use of plant extracts or their active components [1]
Assessment of the antigenotoxicity of SM and SB via the alkaline comet assay demonstrated reduced DNA damage (% DNA in tail) in cells cotreated with SM or SB and methyl methanesulfonate (MMS) relative to cells treated with the positive control MMS alone (Figures 1 and 2)
SB, the major active constituent of SM, exerted significant protective effect against DNA damage induced by the genotoxic agent MMS, except at a lower concentration (1.0 mg/ml) (Figures 1 and 2)
Summary
According to the World Health Organization, 70% to 95% of the world’s population rely on traditional medicine for primary health care, and most health practices involve the use of plant extracts or their active components [1]. The medicinal properties of S. marianum are attributed to its ability to accumulate bioactive flavonolignan complexes, which are referred to as silymarin (SM). The flavonolignan mixture present in S. marianum mainly consists of silibin (SB), known as silibinin, the major bioactive component of the extract. Analysis of genes related to DNA damage, carcinogenesis, and/or chemoprevention can help elucidate the mechanisms by which dietary supplements can exert protective effects on DNA [9,10,11,12,13]. Considering the biological activities presented by SM and SB, as well as their widespread use as herbal medicines, the present study aimed to evaluate the antigenotoxic activities of SM and SB using the comet assay and to evaluate the expression patterns of genes that are known to be associated with carcinogenesis and chemopreventive processes
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