Abstract
In recent years, chronic degenerative diseases such as certain types of cancers, are becoming an evident issue. DNA damage has been for long recognized as a causal factor for cancer development because mutations or chromosomal aberrations affect oncogenes and tumor suppressor genes leading cells to malignant transformation and to the subsequent cancerous growth. Medicinal plants are often used for the prevention or treatment of various diseases with great scientific interest. Among the medicinal plants distributed in the Mediterranean region, Fraxinus angustifolia Vahl. has been used in traditional medicine for its remarkable curative properties. However, in spite of this popularity, little works have been performed on the activity so that further studies should be performed to investigate in depth the antimutagenic, antigenotoxic and antiproliferative activities of the plant. Thus, the present study was aimed to the evaluation of the potential antimutagenic, antigenotoxic and antiproliferative properties of leaves and stem bark extracts of this well-known tree. Antimutagenic activity was evaluated by Salmonella mutagenicity assay in Salmonella typhimurium TA98 and TA100 strains. The antigenotoxic potential was assessed by umu test in the strain of S. typhimurium TA1535/pSK1002. Antiproliferative activity was studied on human hepatoblastoma (HepG-2) and on breast adenocarcinoma (MCF-7) cell lines by MTT assay. Furthermore, the antiproliferative activity observed on cancer cells was compared with that on the human normal-like fibroblasts (TelCOFS02MA) and the selectivity index was calculated to understand if extracts were able to exert selective toxicity towards cancer cells. Moreover, phenolic compounds are plant substances with a large spectrum of biochemical activities with antioxidant, antimutagenic and anticarcinogenic effects. Based on the strong evidence of biological activities of phenolic compounds, the study was focused on the determination of total phenolics and flavonoids contents, and the phytochemical composition of the extracts assessed by LC/MS. The ethanol extracts of both leaves and stem barks showed significant from moderate to strong antimutagenic and antigenotoxic effects. In addition, selective cytotoxicity towards cancer cells was shown by ethanolic leaves extract and aqueous/chloroform leaves and stem bark extracts. The latter showed high levels of total phenolic contents among all the other extracts. Identified phenylethanoids (calceolariosides, verbascoside) and secoiridoids (oleuropein and ligstroside) could be responsible for the demonstrated broad spectrum of healthy properties.
Highlights
Natural products still play a leading role in the treatment of various diseases in diverse forms e.g. extracts, fractions or as a chemical platform
It was proven that several polyphenols, including quercetin, can bind to DNA and this direct interaction may be an important mechanism of bacterial mutagenicity, even those polyphenols that are negative in bacterial systems may be clastogenic in mammalian cells [45]
The results of the present study showed that F. angustifolia Vahl. leaves and stem bark extracts alone had no mutagenic effect on the tested strains, either in the presence or absence of metabolic activation
Summary
Natural products still play a leading role in the treatment of various diseases in diverse forms e.g. extracts, fractions or as a chemical platform. One of the hottest topic in medicine is focused on natural bioactive products in the prevention and/or treatment of chronic diseases which have been characterized as the public health challenge of the 21st century. As explained by Lunenfeld and Stratton [2], in developed countries the rise in healthcare systems and life expectancy, as well as the decrease in fertility rate mainly due to chromosomal abnormalities lead to a rapid increase in the world population aging with consequent chronic degenerative disease increase. Antimutagenic, antigenotoxic and anticarcinogenic substances play a major role in the primary prevention of cancer development [4, 5]
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