The Inhibitory Effect of Spices and Flavonoid Compounds on Formation of 2-amino-1-methyl-6-Phenylimidazo [4,5-b] Pyridine (PhIP) in a Model System

Zaher Al-bashabsheh^1, , J. Scott Smith¹, Ziyi Linghu¹ and Faris Karim¹

¹Food Science Institute., Kansas State University, Manhattan, KS 66506, U.S.A.

Cite this paper:
Zaher Al-bashabsheh, J. Scott Smith, Ziyi Linghu and Faris Karim. The Inhibitory Effect of Spices and Flavonoid Compounds on Formation of 2-amino-1-methyl-6-Phenylimidazo [4,5-b] Pyridine (PhIP) in a Model System. Journal of Food and Nutrition Research. 2020; 8(12):746-751. doi: 10.12691/jfnr-8-12-8

Abstract

Heterocyclic amines (HCAs) are a class of mutagenic and carcinogenic compounds generated when muscle foods are cooked at high temperatures. Exposure to HCAs has been linked to human cancers, among them colon, prostate, breast, and pancreatic cancers. 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) is a common, potentially harmful HCA that forms via the Maillard reaction. The health consequences of consuming HCAs have caused the International Agency for Research on Cancer (IARC) to list PhIP as a “possible human carcinogen.” Spices and flavonoid compounds have received considerable attention for their beneficial effect against HCA formation in our daily foods. In this study, a model system with 0.011 mmol glucose, 0.022 mmol creatinine, and 0.022 mmol phenylalanine in 90:10 diethylene glycol/water (v/v) was heat-treated at 180°C for 1 hour to test the formation of PhIP. Spices such as black pepper oil, piperine, D-limonene, P-cymene, and capsaicin and flavonoid compounds such as quercetin, apigenin, genistin, phlorizin, and catechin were added individually to the model system at three concentrations (125, 625, and 1250 ppm) to test their effect on PhIP formation. The PhIP contents were assessed using High-Performance Liquid Chromatography (HPLC). The results indicate that four out of five components of spices: black pepper oil, piperine, D-limonene, and capsaicin significantly (p < 0.05) reduced PhIP formation, while P-cymene had no significant effect on PhIP formation. All flavonoid compounds also had a significant (p < 0.05) effect on PhIP formation. These findings provide valuable information about spices and flavonoid compounds as protective agents against HCA formation.

Keywords:
heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[45-b] pyridine spices flavonoid compounds model system

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Murkovic M. Formation of heterocyclic aromatic amines in model systems. Journal of Chromatography B. 2004; 802(1): 3-10.
[2]	Widmark E. Presence of cancer-producing substances in roasted food. Nature. 1939; 143(3632): 984.
[3]	Gibis M, Kruwinnus M, Weiss J. Impact of different pan-frying conditions on the formation of heterocyclic aromatic amines and sensory quality in fried bacon. Food Chemistry. 2015; 68:383-389.
[4]	Norell SE, Ahlbom A, Erwald R, JACOBSON G, Lindberg-Navier I, Olin R, TőRNBERG B, Wiechel K. Diet and pancreatic cancer: a case-control study. American Journal of Epidemiology. 1986; 124(6): 894-902.
[5]	Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Speizer FE. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. New England Journal of Medicine. 1990; 323(24): 1664-1672.
[6]	International Agency for Research on Cancer. Monographs on the Evaluation of Carcinogenic Risk to Humans. Vol. 56. Lyon, France: IARC. 1993.
[7]	National Toxicology Program (NTP), U.S. Department of Health and Human Services. Heterocyclic Amines. Report on Carcinogens. 12th ed. U.S. Department of Health and Human Services. 2011; p 220-4.
[8]	Lynch AM, Knize MG, Boobis AR, Gooderham NJ, Davies DS, Murray S. Intra- and interindividual variability in systemic exposure in humans to 2-amino-3,8 dimethylimidazo[4,5-f] quinoxaline and 2-amino-1-methyl- 6-phenylimidazo[4,5-b] pyridine, carcinogens present in cooked beef. Cancer Research. 1992; 52(22): 6216-6223.
[9]	Zöchling S, Murkovic M, Pfannhauser W. Effects of industrially produced flavours with pro-and antioxidative properties on the formation of the heterocyclic amine PhIP in a model system. Journal of Biochemical and Biophysical Methods. 2002; 53(1-3): 37-44.
[10]	Bordas M, Moyano E, Puignou L, Galceran M. Formation and stability of heterocyclic amines in a meat flavor model system: Effect of temperature, time and precursors. Journal of Chromatography B. 2004; 802(1):11-7.
[11]	Cheng K, Wu Q, Zheng ZP, Peng X, Simon JE, Chen F, Wang M. Inhibitory effect of fruit extracts on the formation of heterocyclic amines. Journal of Agricultural and Food Chemistry. 2007; 55(25): 10359-10365.
[12]	Kikugawa K. Prevention of mutagen formation in heated meats and model systems. Mutagenesis. 2004; 19(6): 431-439.
[13]	Vitaglione P, Fogliano V. Use of antioxidants to minimize the human health risk associated to mutagenic/carcinogenic heterocyclic amines in food. Journal of Chromatography B. 2004; 802(1):189-199.
[14]	Zachariah TJ, Parthasarathy V. Black pepper. Chemistry of Spices. 2008; 196, 21.
[15]	Singletary K. Black pepper: overview of health benefits. Nutrition Today. 2010; 45(1): 43-47.
[16]	Darshan S, Doreswamy R. Patented antiinflammatory plant drug development from traditional medicine. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2004; 18(5): 343-357.
[17]	Oz F, Kaya M. The inhibitory effect of black pepper on formation of heterocyclic aromatic amines in high-fat meatball. Food Control. 2011; 22(3-4):596-600.
[18]	Sun J. D-Limonene: safety and clinical applications. Alternative Medicine Review. 2007; 12(3): 259.
[19]	Faustino J, Barroca MJ, Guiné R. Study of the drying kinetics of green bell pepper and chemical characterization. Food and Bioproducts Processing. 2007; 85(3):163-170.
[20]	KumAr OA, TATA SS. Ascorbic acid contents in chili peppers (Capsicum L.). Notulae Scientia Biologicae. 2009; 1(1):50-52.
[21]	Nishino H, Murakoshi M, Tokuda H, Satomi Y. Cancer prevention by carotenoids. Archives of Biochemistry and Biophysics. 2009; 483(2):165-168.
[22]	Zeng M, Zhang M, He Z, Qin F, Tao G, Zhang S, Gao Y, Chen J. Inhibitory profiles of chili pepper and capsaicin on heterocyclic amine formation in roast beef patties. Food Chemistry. 2017; 221: 404-411.
[23]	Liu C, Zheng Y, Lu J, Zhang Z, Fan S, Wu D, Ma J. Quercetin protects rat liver against lead-induced oxidative stress and apoptosis. Environmental Toxicology and Pharmacology. 2010; 29(2): 158-166.
[24]	Cheng K, Chen F, Wang M. Inhibitory activities of dietary phenolic compounds on heterocyclic amine formation in both chemical model system and beef patties. Molecular Nutrition & Food Research. 2007; 51(8):969-976.
[25]	Puangsombat K, Gadgil P, Houser TA, Hunt MC, Smith J.S. Occurrence of heterocyclic amines in cooked meat products. Meat Science. 2012; 90(3):739-746.
[26]	Kelly EL, Smith J.S. Formation and inhibition of the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) in a model system (Doctoral dissertation, Kansas State University). 2015.
[27]	Gülçin İ. The antioxidant and radical scavenging activities of black pepper (Piper nigrum) seeds. International Journal of Food Sciences and Nutrition. 2005; 56(7): 491-499.
[28]	Ahn J, Grün IU. Heterocyclic amines: 2. Inhibitory effects of natural extracts on the formation of polar and nonpolar heterocyclic amines in cooked beef. Journal of Food Science. 2005; 70(4):C263-C268.
[29]	Oguri A, Suda M, Totsuka Y, Sugimura T, Wakabayashi K. Inhibitory effects of antioxidants on formation of heterocyclic amines. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 1998; 402(1): 237-245.
[30]	Zeng M, He Z, Zheng Z, Qin F, Tao G, Zhang S, Gao Y, Chen J. Effect of six Chinesespices on heterocyclic amine profiles in roast beef patties by ultra-performance liquid chromatography-tandem mass spectrometry and principal component analysis. Journal of Agricultural and Food Chemistry. 2014; 62(40): 9908-9915.
[31]	Khanduja K, Gandhi R, Pathania V, Syal N. Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice. Food and Chemical Toxicology. 1999; 37(4): 313-318.
[32]	Yang K, Lamprecht SA, Liu Y, Shinozaki H, Fan K, Leung D, Newmark H, Steele VE, Kelloff GJ, Lipkin M. Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon. Carcinogenesis. 2000; 21(9): 1655-1660.
[33]	Seufi AM, Ibrahim SS, Elmaghraby TK, Hafez EE. Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/antioxidant activity: molecular and histological evidences. Journal of Experimental & Clinical Cancer Research. 2009; 28(1):80.
[34]	Zhang Y, Luo Z, Shao Z, Yu C, Wang S. Effects of antioxidants of bamboo leaves and flavonoids on 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) formation in chemical model systems. Journal of Agricultural and Food Chemistry. 2014; 62(20):4798-4802.
[35]	Yu C, Shao Z, Liu B, Zhang Y, Wang S. Inhibition of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) formation by alkoxy radical scavenging of flavonoids and their quantitative structure-activity relationship in a model system. Journal of Food Science. 2016; 81(8):C1908-C1913.
[36]	Zhu Q, Zhang S, Wang M, Chen J, Zheng Z. Inhibitory effects of selected dietary flavonoids on the formation of total heterocyclic amines and 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in roast beef patties and in chemical models. Food & Function. 2016; 7(2):1057-1066.
[37]	Shao Z, Han Z, Zhang J, Zhang Y, Wang S. Inhibition effects of flavonoids on 2- amino-3, 8-dimethylimidazo [4, 5-f] quinoxaline and 2-amino-3, 7, 8-trimethylimidazo [4, 5-f] quinoxaline formation and alkoxy radical scavenging capabilities of flavonoids in a model system. Journal of the Science of Food and Agriculture. 2018; 98(8): 2908-2914.