Pharmacological Implications of Natural Products of Fruits and Vegetable Origin on the Activity of Cytochrome P450 Enzymes

Eugene Ohams Ohanme *

Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Ebonyi State, Nigeria.

Ogbonnaya Nnabuike Iganga

Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Ebonyi State, Nigeria.

Casimir Chijioke Ofor

Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Ebonyi State, Nigeria.

Uzochukwu Ofonakara

Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Ebonyi State, Nigeria.

Amucheukwu Veronica Nwafor

Department Obstetrics and Gynaecology, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Ebonyi State, Nigeria.

Clementina, Nkiru Eze

Basic School of Midwifery, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria.

Kenneth Eze Etu

Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Ebonyi State, Nigeria.

Benjamin Nwafocha Nwakelu

Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Ebonyi State, Nigeria.

Chiazor Prince Unekwe

Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nigeria.

*Author to whom correspondence should be addressed.


Abstract

The primary goal of drug metabolism, sometimes referred to as pharmacokinetic process, is to change a medication's chemical structure to make it more readily excretable. Typically, phase I and phase II reactions involve this mechanism. Xenobiotics can stimulate or inhibit the activity of cytochrome P450 (CYP450) enzymes involved in phase I processes. The goal of this research is to clarify the clinical significance of CYP450 induction and inhibition by demonstrating how certain bioactive compounds found in foods or natural products derived from fruits and vegetables can alter CYP450 enzyme activity, impacting drug bioavailability and depuration in addition. The interaction between natural products and foods derived from fruits and vegetables and some pharmaceuticals that can result in toxicity or therapeutic failure will be explained with a few instances. This will make it possible to compile pertinent data regarding appropriate pharmaceutical management in a range of clinical contexts.

Keywords: Fruits, vegetables, cytochrome P450, clinical


How to Cite

Ohanme, E. O., Iganga , O. N., Ofor , C. C., Ofonakara , U., Nwafor , A. V., Eze , C. N., Etu , K. E., Nwakelu , B. N., & Unekwe , C. P. (2024). Pharmacological Implications of Natural Products of Fruits and Vegetable Origin on the Activity of Cytochrome P450 Enzymes. Asian Journal of Research in Medical and Pharmaceutical Sciences, 13(2), 54–71. https://doi.org/10.9734/ajrimps/2024/v13i2255

Downloads

Download data is not yet available.

References

Bushra R, Aslam N, Khan AY: Food-drug interactions. Oman medical journal. 2011; 26(2):77-83.

Niederberger E, Parnham MJ: The impact of diet and exercise on drug responses. 2021; 22(14).

Cascorbi I: Drug interactions--principles, examples and clinical consequences. Deutsches Arzteblatt international. 2012; 109(33-34):546-555;quiz 556.

Choi JH, Ko CM: Food and drug interactions. Journal of lifestyle medicine. 2017;7(1):1-9.

Hussain MS: Patient counseling about herbal-drug interactions. African journal of traditional, complementary, and alternative medicines : AJTCAM. 2011;8(5 Suppl): 152-163.

D'Alessandro C, Benedetti A, Di Paolo A: Interactions between food and drugs, and nutritional status in renal patients: A narrative review. 2022;14(1).

Koziolek M, Alcaro S, Augustijns P, Basit AW, Grimm M, Hens B, Hoad CL, Jedamzik P, Madla CM, Maliepaard M, Marciani L et al: The mechanisms of pharmacokinetic food-drug interactions – a perspective from the ungap group. European Journal of Pharmaceutical Sciences. 2019; 134(31-59.

Carpenter M, Berry H, Pelletier AL: Clinically relevant drug-drug interactions in primary care. American family physician. 2019;99(9):558-564.

Niu J, Straubinger RM, Mager DE: Pharmacodynamic drug-drug interactions. Clin Pharmacol Ther. 2019;105(6):1395-1406.

Hua S, Lye EC: Impact of gastric and bowel surgery on gastrointestinal drug delivery. Drug delivery and translational research. 2023;13(1):37-53.

Patel D, Bertz R, Ren S, Boulton DW, Någård M: A systematic review of gastric acid-reducing agent-mediated drug-drug interactions with orally administered medications. Clinical pharmacokinetics. 2020;59(4):447-462.

Frutiger A, Tanno A, Hwu S, Tiefenauer RF, Vörös J, Nakatsuka N: Nonspecific binding—fundamental concepts and consequences for biosensing applications. Chemical reviews. 2021; 121(13):8095-8160.

Cirilli I, Damiani E, Dludla PV, Hargreaves I, Marcheggiani F: Role of coenzyme q(10) in health and disease: An update on the last 10 years. (2010-2020);(2021):10(8).

Atanasov AG, Zotchev SB, Dirsch VM, Orhan IE, Banach M, Rollinger JM, Barreca D, Weckwerth W, Bauer R, Bayer EA, Majeed M et al: Natural products in drug discovery: Advances and opportunities. Nature Reviews Drug Discovery. 2021;20(3):200-216.

Bailey DG, Dresser G, Arnold JM: Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2013; 185(4):309-316.

Hemaiswarya S, Prabhakar PK, Doble M: Herb-herb and food-drug interactions. In: Herb-drug combinations : A new complementary therapeutic strategy. Hemaiswarya S, Prabhakar PK, Doble M (Eds), Springer Nature Singapore, Singapore. 2022;15-26.

Zhao M, Ma J, Li M: Cytochrome p450 enzymes and drug metabolism in humans. 2021;22(23).

Zhou S, Kestell P, Baguley BC, Paxton JW: Preclinical factors affecting the interindividual variability in the clearance of the investigational anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid. Biochemical Pharmacology. 2003;65(11): 1853-1865.

Preissner SC, Hoffmann MF, Preissner R, Dunkel M, Gewiess A, Preissner S: Polymorphic cytochrome p450 enzymes (cyps) and their role in personalized therapy. PloS one. 2013; 8(12):e82562.

de Andrés F, Altamirano-Tinoco C, Ramírez-Roa R, Montes-Mondragón CF, Dorado P, Peñas-Lledó EM, Llerena A: Relationships between cyp1a2, cyp2c9, cyp2c19, cyp2d6 and cyp3a4 metabolic phenotypes and genotypes in a nicaraguan mestizo population. The Pharmacogenomics Journal. 2021;21(2): 140-151.

Deodhar M, Al Rihani SB: Mechanisms of cyp450 inhibition: Understanding drug-drug interactions due to mechanism-based inhibition in clinical practice. 2020;12(9).

Zhou S, Koh HL, Gao Y, Gong ZY, Lee EJ: Herbal bioactivation: The good, the bad and the ugly. Life Sci. 2004;74(8):935-968.

Ramalingum N, Mahomoodally MF: The therapeutic potential of medicinal foods. Advances in pharmacological sciences. 2014;(354264).

Hakkola J, Hukkanen J, Turpeinen M, Pelkonen O: Inhibition and induction of cyp enzymes in humans: An update. Archives of toxicology. 2020;94(11):3671-3722.

Li Y, Meng Q, Yang M, Liu D, Hou X, Tang L, Wang X, Lyu Y, Chen X, Liu K, Yu AM et al: Current trends in drug metabolism and pharmacokinetics. Acta pharmaceutica Sinica B. 2019; 9(6):1113-1144.

Mittal S, Sawarkar S, Doshi G, Pimple P, Shah J, Bana T: Chapter twenty one - pharmacokinetics and bioavailability of nutraceuticals. In: Industrial application of functional foods, ingredients and nutraceuticals. Anandharamakrishnan C, Subramanian P (Eds), Academic Press. 2023;725-783.

Józsa L, Nemes D: Recent options and techniques to assess improved bioavailability: In vitro and ex vivo methods. 2023;15(4).

Overholser BR, Sowinski KM: Chapter 12 - principles of pharmacokinetics and pharmacodynamics. In: Remington (twenty-third edition). Adejare A (Ed) Academic Press. 2021;219-242.

Tyson RJ, Park CC, Powell JR, Patterson JH, Weiner D, Watkins PB, Gonzalez D: Precision dosing priority criteria: Drug, disease, and patient population variables. Frontiers in pharmacology. 2020; 11(420).

Mukherjee B: Fundamentals of pharmacokinetics. In: Pharmacokinetics: Basics to applications. Mukherjee B (Ed) Springer Singapore, Singapore (2022):1-20.

Tamargo J, Le Heuzey JY, Mabo P: Narrow therapeutic index drugs: A clinical pharmacological consideration to flecainide. European journal of clinical pharmacology. 2015;71(5): 549-567.

Manallack DT: The pk(a) distribution of drugs: Application to drug discovery. Perspectives in medicinal chemistry. 2007; 1(25-38.

Chillistone S, Hardman J: Factors affecting drug absorption and distribution. Anaesthesia & Intensive Care Medicine. 2011;12(4):151-155.

Khan E: Pharmacokinetics and pharmacodynamics. In: Understanding pharmacology in nursing practice. Hood P, Khan E (Eds), Springer International Publishing, Cham. 2020;27-56.

Schulze RJ, Schott MB, Casey CA: The cell biology of the hepatocyte: A membrane trafficking machine. 2019;218 (7):2096-2112.

Blakemore DC, Castro L, Churcher I, Rees DC, Thomas AW, Wilson DM, Wood A: Organic synthesis provides opportunities to transform drug discovery. Nature Chemistry. 2018; 10(4):383-394.

Liu L, Liu Y, Zhou X, Xu Z, Zhang Y, Ji L, Hong C, Li C: Analyzing the metabolic fate of oral administration drugs: A review and state-of-the-art roadmap. Frontiers in pharmacology. 2022; 13(962718.

Stielow M, Witczyńska A, Kubryń N, Fijałkowski Ł: The bioavailability of drugs-the current state of knowledge. 2023; 28(24).

Kamran SH, Rehman K, Akash MSH, Khan A, Laher I: Chapter 12 - impact of physiological factors on drug-metabolizing enzymes: From function to regulation. In: Biochemistry of drug metabolizing enzymes. Hamid Akash MS, Rehman K (Eds), Academic Press. 2022;281-304.

O'Hara K, Wright IM, Schneider JJ, Jones AL, Martin JH: Pharmacokinetics in neonatal prescribing: Evidence base, paradigms and the future. British journal of clinical pharmacology. 2015;80(6):1281-1288.

Tajiri K, Shimizu Y: Liver physiology and liver diseases in the elderly. World journal of gastroenterology. 2013;19(46):8459-8467.

Ryu R, Hebert MF: Chapter 3 - impact of pregnancy on maternal pharmacokinetics of medications. In: Clinical pharmacology during pregnancy (second edition). Mattison D, Halbert L-A (Eds), Academic Press, Boston. 2022;19-46.

Staudinger JL: Disease, drug metabolism, and transporter interactions. Pharmaceutical research. 2013;30(9): 2171-2173.

Yu M, Gouvinhas I, Rocha J, Barros AIRNA: Phytochemical and antioxidant analysis of medicinal and food plants towards bioactive food and pharmaceutical resources. Scientific reports. 2021;11(1): 10041.

Talevi A, Bellera CL: Drug metabolism functionalization (phase i) reactions. In: The adme encyclopedia: A comprehensive guide on biopharmacy and pharmacokinetics. Springer International Publishing, Cham. 2021;1-7.

Jancova P, Anzenbacher P, Anzenbacherova E: Phase ii drug metabolizing enzymes. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2010; 154(2):103-116.

Xu J, Wang X-y, Guo W-z: The cytochrome p450 superfamily: Key players in plant development and defense. Journal of Integrative Agriculture. 2015;14(9):1673-1686.

Munro AW, McLean KJ, Grant JL, Makris TM: Structure and function of the cytochrome p450 peroxygenase enzymes. Biochemical Society transactions. 2018; 46(1):183-196.

Dutt S, Hamza I, Bartnikas TB: Molecular mechanisms of iron and heme metabolism. Annual review of nutrition. 2022;42(311-335.

Zanger UM: P450 monooxygenase system. In: Encyclopedia of molecular pharmacology. Offermanns S, Rosenthal W (Eds), Springer International Publishing, Cham. 2020;1-9.

García-Suástegui WA, Ramos-Chávez LA, Rubio-Osornio M, Calvillo-Velasco M, Atzin-Méndez JA, Guevara J, Silva-Adaya D: The role of cyp2e1 in the drug metabolism or bioactivation in the brain. 2017;(4680732).

Nebert DW, Wikvall K, Miller WL: Human cytochromes p450 in health and disease. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 2013; 368(1612):20120431.

Hakooz N, Hamdan I: Effects of dietary broccoli on human in vivo caffeine metabolism: A pilot study on a group of jordanian volunteers. Current drug metabolism. 2007;8(1):9-15.

Hanley MJ, Cancalon P, Widmer WW, Greenblatt DJ: The effect of grapefruit juice on drug disposition. Expert opinion on drug metabolism & toxicology. 2011;7(3):267-286.

Singh B, Singh JP, Kaur A, Singh N: Phenolic compounds as beneficial phytochemicals in pomegranate (punica granatum l.) peel: A review. Food Chem. 2018;261:(75-86).

Molden E, Spigset O: [fruit and berries--interactions with drugs]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. 2007;127 (24):3218-3220.

Hidaka M, Fujita K, Ogikubo T, Yamasaki K, Iwakiri T, Okumura M, Kodama H, Arimori K: Potent inhibition by star fruit of human cytochrome p450 3a (cyp3a) activity. Drug metabolism and disposition: the biological fate of chemicals. 2004;32 (6):581-583.

Cho HJ, Yoon IS: Pharmacokinetic interactions of herbs with cytochrome p450 and p-glycoprotein. 2015;(736431).

Connolly EL, Sim M, Travica N, Marx W, Beasy G, Lynch GS, Bondonno CP, Lewis JR, Hodgson JM, Blekkenhorst LC: Glucosinolates from cruciferous vegetables and their potential role in chronic disease: Investigating the preclinical and clinical evidence. Frontiers in pharmacology. 2021;12:(767975).

Saito Y, Usami T, Katoh M, Nadai M: Effects of thylakoid-rich spinach extract on the pharmacokinetics of drugs in rats. Biological & pharmaceutical bulletin. 2019; 42(1):103-109.

Olmedilla-Alonso B, Benítez-González AM, Estévez-Santiago R: Assessment of food sources and the intake of the colourless carotenoids phytoene and phytofluene in spain. 2021;13(12).

Pedreschi R, Uarrota V, Fuentealba C, Alvaro JE, Olmedo P, Defilippi BG, Meneses C, Campos-Vargas R: Primary metabolism in avocado fruit. Frontiers in plant science. 2019; 10(795.

Panahi Kokhdan E, Khodabandehloo H: A narrative review on therapeutic potentials of watercress in human disorders. 2021; (5516450).

Peterson S, Lampe JW, Bammler TK, Gross-Steinmeyer K, Eaton DL: Apiaceous vegetable constituents inhibit human cytochrome p-450 1a2 (hcyp1a2) activity and hcyp1a2-mediated mutagenicity of aflatoxin b1. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2006;44(9):1474-1484.

Dahan A, Altman H: Food-drug interaction: Grapefruit juice augments drug bioavailability--mechanism, extent and relevance. European journal of clinical nutrition. 2004;58(1):1-9.

Flanagan D: Understanding the grapefruit-drug interaction. General dentistry. 2005; 53(4):282-285; quiz 286.

Rossi M, Aktar S, Davis M, Hefter Feuss E, Roman-Holba S, Wen K, Gahn C, Caruso F: The grapefruit effect: Interaction between cytochrome p450 and coumarin food components, bergamottin, fraxidin and osthole. X-ray crystal structure and dft studies. Molecules (Basel, Switzerland). 2020;25(14).

Holmberg MT, Tornio A, Neuvonen M, Neuvonen PJ, Backman JT, Niemi M: Grapefruit juice inhibits the metabolic activation of clopidogrel. Clin Pharmacol Ther. 2014;95(3):307-313.

Dahan A, Altman H: Food–drug interaction: Grapefruit juice augments drug bioavailability—mechanism, extent and relevance. European journal of clinical nutrition. 2004;58(1):1-9.

Erlund I: Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition Research. 2004;24(10):851-874.

Hung WL, Suh JH, Wang Y: Chemistry and health effects of furanocoumarins in grapefruit. Journal of food and drug analysis. 2017;25(1):71-83.

Ko JH, Arfuso F, Sethi G, Ahn KS: Pharmacological utilization of bergamottin, derived from grapefruits, in cancer prevention and therapy. 2018;19(12).

Bailey DG: Grapefruit and other fruit juices interactions with medicines. In: Handbook of drug-nutrient interactions. Boullata JI, Armenti VT (Eds), Humana Press, Totowa, NJ. 2010;267-302.

Sica DA: Interaction of grapefruit juice and calcium channel blockers. American Journal of Hypertension. 2006;19(7):768-773.

Bailey DG, Malcolm J, Arnold O, Spence JD: Grapefruit juice-drug interactions. British journal of clinical pharmacology. 1998;46(2):101-110.

Bhagat V, Pandit RA, Ambapurkar S, Sengar M, Kulkarni AP: Drug interactions between antimicrobial and immunosuppressive agents in solid organ transplant recipients. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2021;25(1):67-76.

Bailey DG, Dresser GK: Interactions between grapefruit juice and cardiovascular drugs. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2004; 4(5):281-297.

Oshikoya KA, Oreagba I, Adeyemi O: Sources of drug information and their influence on the prescribing behaviour of doctors in a teaching hospital in ibadan, nigeria. The Pan African medical journal. 2011;9(13.

Sica DA: Calcium channel blocker class heterogeneity: Select aspects of pharmacokinetics and pharmacodynamics. Journal of clinical hypertension (Greenwich, Conn). 2005;7(4 Suppl 1):21-26.

Kiani J, Imam SZ: Medicinal importance of grapefruit juice and its interaction with various drugs. Nutrition Journal. 2007;6(33).

Petric Z, Žuntar I, Putnik P: Food-drug interactions with fruit juices. 2020;10(1).

Wason S, DiGiacinto JL, Davis MW: Effects of grapefruit and seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clinical Therapeutics. 2012; 34(10):2161-2173.

Malhotra S, Bailey DG, Paine MF, Watkins PB: Seville orange juice-felodipine interaction: Comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther. 2001; 69(1):14-23.

Abdelkawy KS, Donia AM, Turner RB, Elbarbry F: Effects of lemon and seville orange juices on the pharmacokinetic properties of sildenafil in healthy subjects. Drugs in R&D. 2016;16(3):271-278.

Bailey DG: Fruit juice inhibition of uptake transport: A new type of food-drug interaction. British journal of clinical pharmacology. 2010;70(5):645-655.

Bailey DG, Dresser GK, Leake BF, Kim RB: Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1a2 (oatp1a2) in grapefruit juice. Clin Pharmacol Ther. 2007;81(4):495-502.

Satoh H, Yamashita F, Tsujimoto M, Murakami H, Koyabu N, Ohtani H, Sawada Y: Citrus juices inhibit the function of human organic anion-transporting polypeptide oatp-b. Drug metabolism and disposition: the biological fate of chemicals. 2005;33(4):518-523.

Lourdes Rg-F, Jorge R-E: Fruit/vegetable-drug interactions: Effects on drug metabolizing enzymes and drug transporters. In: Drug discovery. Hany AE-S (Ed) IntechOpen, Rijeka. 2013;Ch. 1.

Koitabashi Y, Kumai T, Matsumoto N, Watanabe M, Sekine S, Yanagida Y, Kobayashi S: Orange juice increased the bioavailability of pravastatin, 3-hydroxy-3-methylglutaryl coa reductase inhibitor, in rats and healthy human subjects. Life Sci. 2006;78(24):2852-2859.

Lilja JJ, Raaska K, Neuvonen PJ: Effects of orange juice on the pharmacokinetics of atenolol. European journal of clinical pharmacology. 2005;61(5-6):337-340.

Ge S, Duo L, Wang J, GegenZhula, Yang J, Li Z, Tu Y: A unique understanding of traditional medicine of pomegranate, punica granatum l. And its current research status. Journal of ethnopharmacology. 2021;271(113877.

Hidaka M, Okumura M, Fujita K, Ogikubo T, Yamasaki K, Iwakiri T, Setoguchi N, Arimori K: Effects of pomegranate juice on human cytochrome p450 3a (cyp3a) and carbamazepine pharmacokinetics in rats. Drug metabolism and disposition: the biological fate of chemicals. 2005;33 (5):644-648.

Nagata M, Hidaka M, Sekiya H, Kawano Y, Yamasaki K, Okumura M, Arimori K: Effects of pomegranate juice on human cytochrome p450 2c9 and tolbutamide pharmacokinetics in rats. Drug metabolism and disposition: the biological fate of chemicals. 2007;35(2):302-305.

Saruwatari A, Okamura S, Nakajima Y, Narukawa Y, Takeda T, Tamura H: Pomegranate juice inhibits sulfoconjugation in caco-2 human colon carcinoma cells. Journal of medicinal food. 2008;11(4):623-628.

Sivapalan T, Melchini A: Bioavailability of glucoraphanin and sulforaphane from high-glucoraphanin broccoli. 2018;62(18): e1700911.

Felker P, Bunch R, Leung AM: Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism. Nutrition reviews. 2016; 74(4):248-258.

Hwang JH, Lim SB: Antioxidant and anticancer activities of broccoli by-products from different cultivars and maturity stages at harvest. Preventive nutrition and food science. 2015;20(1):8-14.

Miao H, Wang J, Cai C, Chang J, Zhao Y, Wang Q: Accumulation of glucosinolates in broccoli. In: Glucosinolates. Mérillon J-M, Ramawat KG (Eds), Springer International Publishing, Cham. 2017;133-162.

Skupinska K, Misiewicz-Krzeminska I, Lubelska K, Kasprzycka-Guttman T: The effect of isothiocyanates on cyp1a1 and cyp1a2 activities induced by polycyclic aromatic hydrocarbons in mcf7 cells. Toxicology in Vitro. 2009;23(5):763-771.

Fimognari C, Nüsse M, Berti F, Iori R, Cantelli-forti G, Hrelia P: A mixture of isothiocyanates induces cyclin b1- and p53-mediated cell-cycle arrest and apoptosis of human t lymphoblastoid cells. Mutation research. 2004;5541-2(205-214.

Harris KE, Jeffery EH: Sulforaphane and erucin increase mrp1 and mrp2 in human carcinoma cell lines. The Journal of Nutritional Biochemistry. 2008;19(4):246-254.

Yeh CT, Yen GC: Effect of vegetables on human phenolsulfotransferases in relation to their antioxidant activity and total phenolics. Free radical research. 2005;39 (8):893-904.

Schulze H, Hornbacher J: Immunomodulating effect of the consumption of watercress (nasturtium officinale) on exercise-induced inflammation in humans. 2021;10(8).

Giallourou NS, Rowland IR, Rothwell SD, Packham G, Commane DM, Swann JR: Metabolic targets of watercress and peitc in mcf-7 and mcf-10a cells explain differential sensitisation responses to ionising radiation. 2019;58(6):2377-2391.

Leclercq I, Desager JP, Horsmans Y: Inhibition of chlorzoxazone metabolism, a clinical probe for cyp2e1, by a single ingestion of watercress. Clin Pharmacol Ther. 1998;64(2):144-149.

Gupta P, Wright SE, Kim SH, Srivastava SK: Phenethyl isothiocyanate: A comprehensive review of anti-cancer mechanisms. Biochimica et biophysica acta. 2014;1846(2):405-424.

Hofmann T, Kuhnert A, Schubert A, Gill C, Rowland IR, Pool-Zobel BL, Glei M: Modulation of detoxification enzymes by watercress: In vitro and in vivo investigations in human peripheral blood cells. European journal of nutrition. 2009; 48(8):483-491.

Telang U, Ji Y, Morris ME: Abc transporters and isothiocyanates: Potential for pharmacokinetic diet-drug interactions. Biopharmaceutics & drug disposition. 2009;30(7):335-344.

de Figueiredo SM, Filho SA, Nogueira-Machado JA, Caligiorne RB: The anti-oxidant properties of isothiocyanates: A review. Recent patents on endocrine, metabolic & immune drug discovery. 2013; 7(3):213-225.

Ko SH, Park JH, Kim SY, Lee SW, Chun SS, Park E: Antioxidant effects of spinach (spinacia oleracea l.) supplementation in hyperlipidemic rats. Preventive nutrition and food science. 2014; 19(1):19-26.

Dias MC, Pinto D: Plant flavonoids: Chemical characteristics and biological activity. 2021;26(17).

Koh E, Charoenprasert S, Mitchell AE: Effect of organic and conventional cropping systems on ascorbic acid, vitamin c, flavonoids, nitrate, and oxalate in 27 varieties of spinach (spinacia oleracea l.). Journal of agricultural and food chemistry. 2012;60(12):3144-3150.

Platt KL, Edenharder R, Aderhold S, Muckel E, Glatt H: Fruits and vegetables protect against the genotoxicity of heterocyclic aromatic amines activated by human xenobiotic-metabolizing enzymes expressed in immortal mammalian cells. Mutat Res. 2010;703(2):90-98.

Ali MY, Sina AA: Nutritional composition and bioactive compounds in tomatoes and their impact on human health and disease: A review. 2020;10(1).

Collins EJ, Bowyer C, Tsouza A, Chopra M: Tomatoes: An extensive review of the associated health impacts of tomatoes and factors that can affect their cultivation. Biology. 2022;11(2).

Agarwal S, Rao AV: Tomato lycopene and its role in human health and chronic diseases. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2000; 163(6):739-744.

Santes-Palacios R, Marroquín-Pérez AL, Hernández-Ojeda SL, Camacho-Carranza R, Govezensky T, Espinosa-Aguirre JJ. Human cyp1a1 inhibition by flavonoids. Toxicology In vitro : An international journal published in association with BIBRA. 2020; 62(104681.

Wang H, Leung LK: The carotenoid lycopene differentially regulates phase i and ii enzymes in dimethylbenz[a]anthracene-induced mcf-7 cells. Nutrition. 2010;26(11-12):1181-1187.

Veeramachaneni S, Ausman LM, Choi SW, Russell RM, Wang XD: High dose lycopene supplementation increases hepatic cytochrome p4502e1 protein and inflammation in alcohol-fed rats. The Journal of nutrition. 2008;138(7):1329-1335.

Sharma KD, Karki S, Thakur NS, Attri S: Chemical composition, functional properties and processing of carrot-a review. Journal of food science and technology. 2012;49(1):22-32.

Bradfield CA, Chang Y, Bjeldanes LF: Effects of commonly consumed vegetables on hepatic xenobiotic-metabolizing enzymes in the mouse. Food and Chemical Toxicology. 1985; 23(10):899-904.

Villa-Rodríguez JA, Molina-Corral FJ, Ayala-Zavala JF, Olivas GI, González-Aguilar GA: Effect of maturity stage on the content of fatty acids and antioxidant activity of ‘hass’ avocado. Food research international. 2011;44(5):1231-1237.

Thompson SV, Bailey MA, Taylor AM, Kaczmarek JL, Mysonhimer AR, Edwards CG, Reeser GE, Burd NA, Khan NA, Holscher HD: Avocado consumption alters gastrointestinal bacteria abundance and microbial metabolite concentrations among adults with overweight or obesity: A randomized controlled trial. The Journal of nutrition. 2021;151(4):753-762.

Ding H, Chin Y-W, Kinghorn AD, D’Ambrosio SM: Chemopreventive characteristics of avocado fruit. Seminars in cancer biology. 2007;17(5):386-394.

Norwood DA, Parke CK, Rappa LR: A comprehensive review of potential warfarin-fruit interactions. Journal of pharmacy practice. 2015;28(6): 561-571.