Punicalagin and ellagic acid demonstrate antimutagenic activity and inhibition of benzo[a]pyrene induced DNA adducts.

Maryam Zahin,Iqbal Ahmad,Farrukh Aqil,Ramesh C Gupta

doi:10.1155/2014/467465

Maryam Zahin, Iqbal Ahmad + Show 2 more

Open Access

https://doi.org/10.1155/2014/467465

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Abstract

Punicalagin (PC) is an ellagitannin found in the fruit peel of Punica granatum. We have demonstrated antioxidant and antigenotoxic properties of Punica granatum and showed that PC and ellagic acid (EA) are its major constituents. In this study, we demonstrate the antimutagenic potential, inhibition of BP-induced DNA damage, and antiproliferative activity of PC and EA. Incubation of BP with rat liver microsomes, appropriate cofactors, and DNA in the presence of vehicle or PC and EA showed significant inhibition of the resultant DNA adducts, with essentially complete inhibition (97%) at 40 μM by PC and 77% inhibition by EA. Antimutagenicity was tested by Ames test. PC and EA dose-dependently and markedly antagonized the effect of tested mutagens, sodium azide, methyl methanesulfonate, benzo[a]pyrene, and 2-aminoflourine, with maximum inhibition of mutagenicity up to 90 percent. Almost all the doses tested (50–500 μM) exhibited significant antimutagenicity. A profound antiproliferative effect on human lung cancer cells was also shown with PC and EA. Together, our data show that PC and EA are pomegranate bioactives responsible for inhibition of BP-induced DNA adducts and strong antimutagenic, antiproliferative activities. However, these compounds are to be evaluated in suitable animal model to assess their therapeutic efficacy against cancer.

Highlights

Over the past few decades, tremendous outcomes have been resulted by exploring antioxidant and antimutagenic potential of medicinal plants
It is widely accepted that oxidative modification of DNA, protein, lipids, and small cellular molecules by both exogenous and endogenous reactive oxygen species including free radicals and nonfree radicals plays an important role in a wide range of common diseases including cancer and age related degenerative diseases [1, 2]
Natural antimutagens from edible and medicinal plants are of particular importance because they may be useful for inhibition of DNA adducts leading to human cancer prevention and have no undesirable xenobiotic effects on living organisms [11, 12]

Summary

Introduction

Over the past few decades, tremendous outcomes have been resulted by exploring antioxidant and antimutagenic potential of medicinal plants. The human body possesses innate defence mechanisms to counter free radicals Plant secondary metabolites such as phenolics, flavonoids, and terpenoids play an important role in the defence against free radicals [3]. These natural antioxidants may reduce or inhibit the mutagenic potential of mutagens, promutagens, and carcinogens [4, 5]. Natural antimutagens from edible and medicinal plants are of particular importance because they may be useful for inhibition of DNA adducts leading to human cancer prevention and have no undesirable xenobiotic effects on living organisms [11, 12]. We examined protective effect of PC and EA against BP-induced DNA adducts and antiproliferative activity against lung cancer cells in vitro

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