https://doi.org/10.4081/jbr.2024.11721
Cytochrome p450 and innovative nutraceutical products
Submitted: September 5, 2023
Accepted: February 17, 2024
Published: March 8, 2024
Accepted: February 17, 2024
Abstract Views: 931
PDF: 265
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Dietary supplements are products that are ingested in addition to the regular diet to provide additional health-promoting nutrients. Dietary supplements are defined and regulated differently in the European Union (EU) and the United States (US). A fundamental aspect, besides the one related to the composition of the various products on the market, is linked to their quality, both from a nutritional and a pharmacological point of view. Concerning the knowledge of the metabolic aspects, the analysis of the interference, as an inductive or an inhibitory effect, of the p450 enzyme on individual preparations of supplements, is crucial. In this study, we present the results of the interference analysis of a new nutraceutical product based on 38% Bergamot Polyphenolic Fraction BPF® (Citrus bergamia Risso et Poit.), Pomegranate (Punica granatum) and Citrus fruits (Citrus aurantium var. dulcis, Citrus maxima Burm. Merr, Citrus paradisi Macfad) extract with cytochrome p450, showing that the product has limited activity on the cytochromes involved in most of human drug metabolism. This nutraceutical product is to be considered safe and potentially useful in the context of multiple treatments, not interfering with the traditional chronic therapies of patients. These findings open the door to modern "pharma-grade" nutraceuticals, expanding the safety and quality profiles of these new products.
Guo J, Zhu X, Badawy S, et al. Metabolism and mechanism of human cytochrome p450 enzyme 1A2. Curr Drug Metab 2021;22:40-9.
DOI: https://doi.org/10.2174/1389200221999210101233135
Backman JT, Filppula AM, Niemi M, Neuvonen PJ. Role of cytochrome p450 2C8 in drug metabolism and interactions. Pharmacol Rev 2016;68:168-241.
DOI: https://doi.org/10.1124/pr.115.011411
Zhao M, Ma J, Li M, et al. Cytochrome P450 enzymes and drug metabolism in humans. Int J Mol Sci 2021;22:12808.
DOI: https://doi.org/10.3390/ijms222312808
Fisher CD, Lickteig AJ, Augustine LM et al. Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab Dispos 2009;37:2087-94.
DOI: https://doi.org/10.1124/dmd.109.027466
Manikandan P, Nagini S. Cytochrome p450 structure, function and clinical significance: a review. Curr Drug Targets 2018;19:38-54.
DOI: https://doi.org/10.2174/1389450118666170125144557
Guengerich FP, Waterman MR, Egli M. Recent structural insights into cytochrome p450 function. Trends Pharmacol Sci 2016;37:625-40.
DOI: https://doi.org/10.1016/j.tips.2016.05.006
Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 2002;3:229-43.
DOI: https://doi.org/10.1517/14622416.3.2.229
Kaburaki S, Yoshimura E, Miyamoto Y, et al. Hepatic drug metabolism in older people with body composition changes. Geriatr Gerontol Int 2022;22:449-54.
DOI: https://doi.org/10.1111/ggi.14380
Tajiri K, Shimizu Y. Liver physiology and liver diseases in the elderly. World J Gastroenterol 2013;19:8459-67.
DOI: https://doi.org/10.3748/wjg.v19.i46.8459
Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 2007;76:391-6.
Cozza KL, Amrstrong SC, Oesterheld JR. Concise guide to drug interaction principles for medical practice: cytochrome P450, UGTs, P-glycoproteins. Arlington: American Psychiatric Publishing; 2003.
Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome p450 3A4 inhibition. Clin Pharmacokinet 2000;38:41–57.
DOI: https://doi.org/10.2165/00003088-200038010-00003
Osadnik T, Goławski M, Lewandowski P, et al. A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults. Pharmacol Res 2022;183:106402.
DOI: https://doi.org/10.1016/j.phrs.2022.106402
Huang Y, Tocmo R, Nauman MC, et al. Defining the cholesterol lowering mechanism of bergamot (Citrus bergamia) extract in hepG2 and caco-2 cells. Nutrients 2021;13:3156.
DOI: https://doi.org/10.3390/nu13093156
Nauman MC, Johnson JJ. Clinical application of bergamot (Citrus bergamia) for reducing high cholesterol and cardiovascular disease markers. Integr Food Nutr Metab 2019;6:10.15761/IFNM.1000249.
DOI: https://doi.org/10.15761/IFNM.1000249
Salerno R, Casale F, Calandruccio C, Procopio A. Characterization of flavonoids in Citrus bergamia (bergamot) polyphenolic fraction by liquid chromatography–high resolution mass spectrometry (LC/HRMS). PharmaNutrition 2016;4:S1-S7.
DOI: https://doi.org/10.1016/j.phanu.2015.10.001
Carresi C, Gliozzi M, Musolino V, et al. The effect of natural antioxidants in the development of metabolic syndrome: focus on bergamot polyphenolic fraction. Nutrients 2020;12:1504
DOI: https://doi.org/10.3390/nu12051504
Vučić V, Grabež M. Composition and potential health benefits of pomegranate: a review. Curr Pharm Des 2019;25:1817-27.
DOI: https://doi.org/10.2174/1381612825666190708183941
Zarfeshany A, Asgary S, Javanmard SH. Potent health effects of pomegranate. Adv Biomed Res 2014;3:100.
DOI: https://doi.org/10.4103/2277-9175.129371
Pirzadeh M, Caporaso N. Pomegranate as a source of bioactive constituents: a review on their characterization, properties and applications. Crit Rev Food Sci Nutr 2021;61:982-99.
DOI: https://doi.org/10.1080/10408398.2020.1749825
Michicotl-Meneses MM, Thompson-Bonilla MDR, Reyes-López CA, et al. Inflammation markers in adipose tissue and cardiovascular risk reduction by pomegranate juice in obesity induced by a hypercaloric diet in wistar rats. Nutrients 2021;13:2577.
DOI: https://doi.org/10.3390/nu13082577
Akaberi M, Boghrati Z, Sahebkar A, Emami SA. Therapeutic potential of pomegranate in metabolic disorders. Adv Exp Med Biol 2021;1328:421-40.
DOI: https://doi.org/10.1007/978-3-030-73234-9_28
Laurindo LF, Barbalho SM, Marquess AR, et al. Pomegranate (Punica granatum L.) and metabolic syndrome risk factors and outcomes: a systematic review of clinical studies. Nutrients 2022;14:1665.
DOI: https://doi.org/10.3390/nu14081665
Mas-Capdevila A, Teichenne J, Domenech-Coca C, et al. Effect of hesperidin on cardiovascular disease risk factors: the role of intestinal microbiota on hesperidin bioavailability. Nutrients 2020;12:1488.
DOI: https://doi.org/10.3390/nu12051488
De Blasio A, D’Anneo A, Lauricella M, et al. The beneficial effects of essential oils in anti-obesity treatment. Int J Mol Sci 2021;22:11832.
DOI: https://doi.org/10.3390/ijms222111832
Favela-Hernández JM, González-Santiago O, Ramírez-Cabrera MA, et al. Chemistry and pharmacology of Citrus sinensis. Molecules 2016;21:247.
DOI: https://doi.org/10.3390/molecules21020247
Mallick N, Khan RA. Antihyperlipidemic effects of Citrus sinensis, Citrus paradisi, and their combinations. J Pharm Bioallied Sci 2016;8:112-8.
DOI: https://doi.org/10.4103/0975-7406.171727
Oboh G, Bello FO, Ademosun AO. Hypocholesterolemic properties of grapefruit (Citrus paradisii) and shaddock (Citrus maxima) juices and inhibition of angiotensin-1-converting enzyme activity. J Food Drug Anal 2014;22:477-84.
DOI: https://doi.org/10.1016/j.jfda.2014.06.005
Denkova-Kostova R, Teneva D, Tomova T, et al. Chemical composition, antioxidant and antimicrobial activity of essential oils from tangerine (Citrus reticulata L.), grapefruit (Citrus paradisi L.), lemon (Citrus lemon L.) and cinnamon (Cinnamomum zeylanicum Blume). Z Naturforsch C J Biosci 2020;76:175-85.
DOI: https://doi.org/10.1515/znc-2020-0126
Cristóbal-Luna JM, Álvarez-González I, Madrigal-Bujaidar E, Chamorro-Cevallos G. Grapefruit and its biomedical, antigenotoxic and chemopreventive properties. Food Chem Toxicol 2018;112:224-34.
DOI: https://doi.org/10.1016/j.fct.2017.12.038
Cali JJ, Ma D, Sobol M, et al. Luminogenic cytochrome P450 assays. Expert Opin Drug Metab Toxicol 2006;2:629-45.
DOI: https://doi.org/10.1517/17425255.2.4.629
Krippendorff BF, Lienau P, Reichel A, Huisinga W. Optimizing classification of drug-drug interaction potential for CYP450 isoenzyme inhibition assays in early drug discovery. J Biomol Screen 2007;12:92-9.
DOI: https://doi.org/10.1177/1087057106295897
Gujjarlamudi HB. Polytherapy and drug interactions in elderly J Midlife Health 2016;7:105-7.
DOI: https://doi.org/10.4103/0976-7800.191021
Montamat SC, Cusack BJ, Vestal RE. Management of drug therapy in the elderly. N Engl J Med 1989;321:303-9.
DOI: https://doi.org/10.1056/NEJM198908033210507
Błeszyńska E, Wierucki Ł, Zdrojewski T, Renke M. Pharmacological interactions in the elderly. Medicina (Kaunas) 2020;56:320.
DOI: https://doi.org/10.3390/medicina56070320
Gougis P, Hilmi M, Geraud A, et al. Potential cytochrome p450-mediated pharmacokinetic interactions between herbs, food, and dietary supplements and cancer treatments. Crit Rev Oncol Hematol 2021;166:103342.
DOI: https://doi.org/10.1016/j.critrevonc.2021.103342
Granato D, Barba FJ, Bursać Kovačević D, et al. Functional foods: product development, technological trends, efficacy testing, and safety. Annu Rev Food Sci Technol 2020;11:93-118.
DOI: https://doi.org/10.1146/annurev-food-032519-051708
Kreider RB, Jäger R, Purpura M. Bioavailability, efficacy, safety, and regulatory status of creatine and related compounds: a critical review. Nutrients 2022;14:1035.
DOI: https://doi.org/10.3390/nu14051035
Younes M, Aggett P, Aguilar F, et al. Scientific opinion on the safety of monacolins in red yeast rice. EFSA panel on food additives and nutrient sources added to food (ANS); EFSA J 2018;16:e05368.
DOI: https://doi.org/10.2903/j.efsa.2018.5368
Commission regulation (EU) 2022/860 of 1 June 2022 amending annex III to regulation (EC) No 1925/2006 of the European Parliament and of the Council as regards monacolins from red yeast rice C/2022/3493 OJ L 151, 2.6.2022, p. 37-41.
Matura JM, Shea LA, Bankes VA. Dietary supplements, cytochrome metabolism, and pharmacogenetic considerations. Ir J Med Sci 2022;191:2357-65.
DOI: https://doi.org/10.1007/s11845-021-02828-4
How to Cite
Frati, F., Torello, G., & Di Cara, G. (2024). Cytochrome p450 and innovative nutraceutical products. Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale, 97(1). https://doi.org/10.4081/jbr.2024.11721
Copyright (c) 2024 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.