Muhammad Ishaque Ph.D Botany 02-arid-270 Lycopene's effects on health And diseases Kalai Selvan, A. Vijayakumar, K. Suresh Kumar and Gyanedra Nath Singh,

Muhammad IshaquePh.D Botany02-arid-270

Lycopene's effects on health

And diseases

Kalai Selvan, A. Vijayakumar, K. Suresh Kumar and Gyanedra Nath Singh, 2011. Lycopene's Effects on Health and Diseases, A comprehensive review of the literature. Natural medicine journal: 11 (4): Pp. 87-95.

Lycopene

A carotenoid , Red, fat-soluble pigment found in certain plants and microorganisms (but not in animals), where it serves as an accessory light-gathering pigment and protects them from ultraviolet radiation.

Mol.Wt 536.89

Mol. Formula C40H56

Lycopene, also known as psi-carotene, is very sensitive to heat and oxidation and is insoluble in water. cis-isomers of lycopene were shown to be more stable, having higher antioxidant potential compared to the all-trans lycopene.8

Amount of lycopene present in different fruits

Gac fruit (Momordica cochinchinensis);Tomatoes (Lycopersicon esculentum)

GAC {Momordica cochinchinensis }

Momordica cochinchinensis is a Southeast Asian fruit found throughout the region from Southern China to Northeastern Australia, including Thailand, Laos, Myanmar, Cambodia and Vietnam.

Baby Jackfruit, Spiny Bitter Gourd, Sweet Gourd, or Cochinchin Gourd

Bioavailability and Pharmacokinetics

Heating tomato juice resulted in trans-to-cis isomerization of lycopene, and on ingestion of this juice, the cis isomers of lycopene appeared to predominate in human serum over the all-trans isomers.12

serum concentrations of lycopene increased after consumption of heated tomato juice mixed with oil, with a peak at 24–48 h after ingestion.12,13

Lycopene is mainly distributed to fatty tissues and organs such as the adrenal glands, liver, and testes

In contrast to other carotenoids, lycopene’s serum values are not regularly reduced by smoking or alcohol consumption, although levels decrease with increasing age.10

Amount of lycopene distribution in various body tissues and organs

Lycopene as Antioxidant ROS have been associated with pathogenesis of various

disorders and diseases such as cancer, cardiovascular disease, osteoporosis, diabetes, and cataracts.14

In one study, lycopene significantly restored the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GR); reduced glutathione (GSH); and decreased levels of the lipid peroxide malondialdehyde (MDA) in hypertensive patients.15

Lycopene at the concentration of 0.31-10 µM prevented the 3-morpholinosydnonimine stress-induced DNA damage in Chinese hamsters; the protective effect is due to the scavenging of intracellular reactive oxygen and/or nitrogen species, reducing the amounts 47.5% and 42.4% respectively.19,20

Antidiabetic and anti hypertension

Kuhad et al reported that lycopene at doses of 1, 2, and 4 mg/kg has significant, dose-dependent antidiabetic action in streptozotocin-induced diabetic rats.22

A single-blind placebo controlled clinical trial found tomato extract (250 mg per day) for 4 weeks reduced blood pressure in patients with grade-1 hypertension.37 The hypocholesterolemic effect of lycopene was also demonstrated in an in vitro study in which it inhibited the activity of 3-hydroxy-3-methyl-glutaryl-CoA an enzyme in cholesterol biosynthesis.38

AtherogenesisAtherogenesis is a disorder of the artery wall

that involves: adhesion of monocytes and lymphocytes to the endothelial cells.

These processes which involve cell adhesion, migration, differentiation, proliferation and cell interaction with the extracellular matrix are regulated by a complex network/cascade of cytokines and growth regulatory peptidesell surface

Lycopene and Cancer human hepatoma cell line SK-Hep-1____ Reduces metastasis human colon cancer HT-29 cells ____ inhibits growth

at very low concentration. The mechanism involved; down-regulation of the

PI-3K/Akt/mTOR signaling pathway.47 Lycopene inhibited platelet-derived growth factor-BB–induced signaling and cell migration in human cultured skin fibroblasts through a direct binding to platelet-derived growth factor-BB.48

Antioxidant effects are increased when lycopene is combined with lutein, and the growth of cancer cells is decreased when it is combined with vitamin D or E.

Cont…. Prostate cancer is the most common male cancer In vitro studies with lycopene have shown induction

of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines.51

At less than 1 μM concentration, lycopene was shown to inhibit human cancer cell growth by interfering with growth factor receptor signaling and cell cycle progression, specifically in prostate cancer cells, without evidence of toxic effects or apoptosis of cells.

Cont…a gene, connexin 43{Tumor suppressor gene

(Cx43)},whose expression is up-regulated by lycopene, allowing

direct intercellular gap junction communication (GJC).GJC is deficient in many human tumors In cell cultures, lycopene has been found to inhibit

breast cancer tumors more efficiently when compared to alpha- and beta-carotene.55,56

Lycopene Therapy in Male Infertility

Excessive ROS-containing free-oxygen radicals have been identified as one of the causes of male infertility.67 Lycopene is a component of the human redox defense mechanism against free radicals. It is found in high concentrations in the testes and seminal plasma (Figure 3), and decreased levels have been demonstrated in men suffering from infertility.67 Oral administration of lycopene (2 mg twice a day for 3 months) to men with infertility significantly improved the sperm concentration in 66% of cases and motility in 73% of cases.67

Summary of the pharmacological actions of lycopene at various dose levels

SUMMARY

References 8. Chasse GA, Mak ML, Deretey E, et al. An ab initio computational study on selected lycopene isomers. J Mol

Struct. 2000;571(1-3):27-37.9. Micozzi MS, Brown ED, Edwards BK, et al. Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men. Am J Clin Nutr. 1992;55(6):1120-1125.10. Gerster H. The potential role of lycopene for human health. J Am Coll Nutr. 1997;16(2):109-126.11. Stahl W, Junghans B, De Boer B, Driomina ES, Briviba K, Sies H. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett. 1998;427(2):305-308.12. Stahl W, Sies H. Uptake of lycopene and its geometrical isomers is greater from heat-processed than from unprocessed tomato juice in humans. J Nutr. 1992;122(11):2161-2166.13. Clinton SK. Lycopene: chemistry, biology, and implications for human health and disease. Nutr Rev. 1998;56(2 pt 1):35-51.14. Ratnam DV, Ankola DD, Bharadwaj V, Sahana DK, Kumar MN. Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J Control Release. 2006;113(3):189-207.15. Bose KS, Agrawal BK. Effect of lycopene from cooked tomatoes on serum antioxidant enzymes, lipid peroxidation rate and lipid profile in coronary heart disease. Singapore Med J. 2007;48(5):415-420.16. Misra R, Mangi S, Joshi S, Mittal S, Gupta SK, Pandey RM. LycoRed as an alternative to hormone replacement therapy in lowering serum lipids and oxidative stress markers: a randomized controlled clinical trial. Obstet Gynecol. 2006;32(3):299-304.17. Hsiao G, Fong TH, Tzu NH, Lin KH, Chou DS, Sheu JR. A potent antioxidant, lycopene, affords neuroprotection against microglia activation and focal cerebral ischemia in rats. In Vivo. 2004;18(3):351-356.18. Varma SD, Kavita RH. Susceptibility of the ocular lens to nitric oxide: implications in cataractogenesis. J Ocul pharmacol Th. 2007;23(2):188-195.19. Muzandu K, Ishizuka M, Sakamoto KQ, et al. Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular modifications. Toxicol Appl Pharmacol. 2006;215(3):330-340.20. Jamshidzadeh A, Baghban M, Azarpira N, Bardbori AM, Niknahad H. Effects of tomato extract on oxidative stress induced toxicity in different organs of rats. Food Chem Toxicol. 2008;46(12):3612-3615.

Cont…. 22. Kuhad A, Sethi R, Chopra S. Lycopene attenuates diabetes-associated cognitive decline in rats. Life Science.

2008;83(3-4):128-134.

37. Bowen P, Chen I, Stacewicz-Sapuntzakis M, et al. Tomato sauce supplementation and prostate cancer: Lycopene accumulation and modulation of biomarkers of carcinogenesis. Experiment Biol Med. 2002;227(10):886-893.38. Bansal P, Gupta SK, Ojha SK, et al. Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury. Mol Cell Biochem. 2006;289(1-2):1-9.

47. Tang FY, Cho HJ, Pai MH, Chen YH. Concomitant supplementation of lycopene and eicosapentaenoic acid inhibits the proliferation of human colon cancer cells. J Nutr Biochem. 2009;20(6):426-434.48. Wu WB, Chiang HS, Fang JY, Hung CF. Inhibitory effect of lycopene on PDGF-BB-induced signaling and migration in human dermal fibroblasts: a possible target for cancer. Biochem Soc Trans. 2007;35(Pt 5):1377-1378.51. Vaishampayan U, Hussain M, Banerjee M, et al. Lycopene and soy isoflavones in the treatment of prostate cancer. Nutr Cancer. 2007;59(1):1-7.

55. Zhang S, Tang G, Russell RM, et al. Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. Am J Clin Nutr. 1997;66(3):626-632.56. Levy J, Bosin E, Feldman B, et al. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta carotene. Nutr Cancer. 1995;24(3):257-266.57. Dorgan JF, Sowell A, Swanson CA, et al. Relationships of serum carotenoids, retinal, alpha-tocopherol and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control. 1998;9(1):89-97.67. Gupta NP, Kumar R. Lycopene therapy in idiopathic male infertility—a preliminary report. Int Urol Nephrol. 2002; 34(3):369-372.

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