Evaluation of antigenotoxic activity of isoliquiritin apioside from Glycyrrhiza glabra L.

Abstract

Prevention of manifestation of events characteristic of carcinogenesis is being emphasized a rational strategy to combat cancer. Reactive oxygen species (ROS) play an important role in tumor initiation through oxidative damage of DNA. In search for lead molecules in cancer chemoprevention from natural products, a fraction ‘Rlicca’ isolated from Glycyrrhiza glabra was studied for modulatory effect against hydrogen peroxide and 4-nitroquinoline-N-oxide induced genotoxicity in Escherichia coli PQ37 using SOS chromotest and in human peripheral blood lymphocytes using the Comet assay. The fraction ‘Rlicca’ at a concentration of 191 μM decreased the SOS inducing potency (SOSIP) of hydrogen peroxide (1.0 mM) and NQO (20 μg/ml) by 83.72% and 68.77%, respectively. In the human blood lymphocytes, ‘Rlicca’ reduced the tail moment induced by hydrogen peroxide (25 μM) and NQO (5 μg/ml) by 88.04% and 76.64%, respectively, using the Comet assay. The spectroscopic data of ‘Rlicca’ fraction revealed it to be isoliquiritin apioside, a chalcone oligoglycoside. This is the first report of isoliquiritin apioside with marked potential to combat oxidative stress-induced genotoxicity.

Introduction

Environmental mutagens and carcinogens are instrumental in initiation, promotion, and progression of several kinds of cancer. The exposure to these xenobiotics is often unavoidable and create a great risk to human health. A complimentary approach is to render the host organism more resistant to the attack of mutagens and carcinogens by supplementing the diet with chemopreventive agents (De Flora and Ferguson, 2005). Intake of sufficient amounts of antimutagens and/or anticarcinogens is believed to confer a preventive effect on the initiation and development of human cancers (Ferguson, 1994). Phytochemicals are secondary metabolic products produced by plants in response to environmental stresses. Thousands of these phytochemicals have been identified and when consumed in human diet may affect chronic disease risk (Messina and Messina, 1996). Evidence from epidemiological and laboratory studies have demonstrated that some plants eaten whole or their active constituents taken in isolation show adequate protective effects against human carcinogenesis and mutagenesis (Surh and Ferguson, 2003). Several plant extracts or their constituents have proved to contain variety of antimutagenic, antigenotoxic substances (Kaur et al., 1998, Kaur et al., 2000, Scassellati-Sforzolini et al., 1999, Pasquini et al., 2002, Nagpal et al., 2000, Saleem et al., 2005, Hayder et al., 2004). One of the ways by which phytochemicals can protect against cell proliferation is by destroying reactive oxidative species (ROS) that initiate carcinogenesis through oxidative damage of DNA (Williams et al., 1989). Oxidative stress can damage DNA, lipids, proteins, and carbohydrates leading to impaired cellular function and enhanced inflammatory reactions (Wang et al., 2006).

Plants are an important component of the health care system in India. Medicinal plants are potential candidates for cancer chemoprevention because they may harbor chemopreventive agents with inhibitory effects on the initiation, promotion and progression of carcinogenesis (Wattenberg, 1985, Surh and Ferguson, 2003). Glycyrrhiza glabra L. is one such medicinal plant whose dried roots and stolons form an important component of various Ayurvedic formulations. There are number of reports of G. glabra with anti-inflammatory, anticancer, antihepatotoxic, antimicrobial, antioxidant, cytoprotective and cytotoxic activities (Vaya et al., 1997, Mitscher et al., 1980, Dhiman and Chawla, 2005). Chalcones are a group of polyphenols abundantly present in plants, which form a group of open chain flavonoids in which two aromatic rings are linked by a three carbon α,β-unsaturated carbonyl system. Many biological activities have been attributed to this group of molecules including their ability to modify cell functions involved in inflammatory responses (Alcaraz et al., 2004). Phytochemicals with pronounced antioxidant and anti-inflammatory effects are anticipated to act as anti-tumor promoters (Surh, 2002).

The medicinal importance of G. glabra, coupled with the dearth of information on chemopreventive potential of chalcone glycosides, prompted us to isolate ‘Rlicca’ a chalcone oligoglycoside and report on its inhibitory activities against oxidative stress-induced DNA damage.