54 Author for correspondence: Dr. M. Salman Khan Associate Professor, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow-226026, U.P., India E-mail: contactskhan@gmail.com Tel.: +91-9044015790 Pleiotropic role of lycopene in protecting various risk factors mediated atherosclerosis Sahir Sultan Alvi, Irfan A. Ansari and M. Salman Khan Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow-226026, U.P., India Received March 25, 2015: Revised April 15, 2015: Accepted April 20, 2015: Published online June 30, 2015 Copyright @ 2015 Ukaaz Publications. All rights reserved. Email: ukaaz@yahoo.com; Website: www.ukaazpublications.com Abstract Lycopene, a carotenoid which is commonly present in vegetable products and fruits, is one of the most effective antioxidants among dietary carotenoids. Dietary ingestion of lycopene has been shown to be inversely associated with risk of chronic diseases, such as cardiovascular diseases (CVDs) and cancer that could be due to its antioxidant potential. Since, a number of risk factors like hypercholesterolemia, smoking, infection/inflammation, etc. are involved in atherosclerosis progression and current remedial strategies are directed towards long term use of chemically synthesized drugs that leads to host of side effects, so a solo safer agent with pleiotropic property is still warranted. Current review summarizes the role of lycopene in risk factors mediated progression of atherosclerotic process on the basis of different in vitro and in vivo experimental evidences in order to explore new possible multiple therapeutic action of lycopene. Key words: Lycopene, atherosclerosis, HMG-CoA reductase, inflammation, LDL, HDL 1. Introduction Cardiovascular diseases (CVDs) have been reckoned amongst the top reasons for early deaths in the world. In 2002, CVDs contributed to approximately one third of entire global deaths, whereas, by the year 2020, it is expected that CVDs will become the leading cause of death and disability worldwide (Ginghina et al., 2011). Therefore, CVD has become an increasing burden to the global economy and a major causative factor for development of CVD and atherosclerosis. There are number of risk factors which induce the progression of atherosclerosis such as hypercholesterolemia, cholesterol induced oxidative stress, elevated levels of low density lipoprotein (LDL) cholesterol, hypertension, tobacco use, cigarette smoking and diabetes. Several epidemiological studies have identified LDL and high density lipoproteins (HDL) as independent risk factors that modulate CVD risks. High levels of plasma LDL-C are directly related to the development of CVD, whereas an inverse association between the incidence of CVD and high concentrations of HDL-C has been observed (Castelli , 1992, 1996). On the other hand, cholesterol-induced oxidative stress is one of the factors that links hypercholesterolemia with atherogenesis (Halliwell, 1996) and is known to produce vascular atherosclerotic lesion and increased oxidative stress in several tissues (Balkan , 2002), including the development of atherosclerosis in the vascular wall through the formation of reactive oxygen species (ROS) (Byon, 2008; Shi et al., 2000). Oxidative modification of LDL have been ANNALS OF PHYTOMEDICINE An International Journal Annals of Phytomedicine 4(1): 54-60, 2015 Journal homepage: www.ukaazpublications.com ISSN : 2393-9885 postulated to play a pivotal role in atherosclerotic process (Bentley, 2002; Steinberg and Witztum, 2002) and has been implicated at both the early and late stages of the pathogenesis of atherosclerosis, during which plaque rupture leads to further clinical events. Besides classical risk factors such as hypercholesterolemia and hypertension; chronic subacute inflammation has been recognized as an important force driving the development of atherosclerosis (Khovidhunkit et al., 2004). Therefore, involvement of inflammation in atherosclerosis has spurred the discovery and adoption of inflammatory biomarkers for cardiovascular risk prediction. Two hypothesis have been proposed to explain the role of inflammatory markers in the pathogenesis of atherosclerosis. One mechanism may be the ongoing inflammation in the artery, stimulated by the oxidized-low-density lipoprotein (ox-LDL), which leads to the production of cytokines that may induce the various acute phase proteins. Alternatively, chronic elevations of acute phase reactants could be due to smoking, chronic infections, obesity and hypercholesterolemia, all of which contribute to the development of atherosclerosis. The second one is hyperlipidemia induced atherosclerosis. In order to reduce the progression of CVDs in the body, different drugs such as statins are used frequently. Statins specifically inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is the rate limiting enzyme of the cholesterol synthesis (Daniel Pella et al., 2005). As it happens with all chemical drugs, long term use of statins also have host of side effects and may incurve problems in terms of toxicity and cost. Therefore, drugs derived from natural products could be a good alternative in the treatment and management of atherosclerosis. Number of studies has demonstrated the role of natural products in inhibiting the HMG-CoA reductase acitivity (Iqbal et al., 2014a; Reddy et al., 2014; Iqbal et al., 2014b) and hypercholesterolemia (Iqbal et al., 2015) as well as atherosclerosis (Khan et al., 2011; Orekhov and