CYP1A2

Cytochrome P450 1A2, abbreviated as CYP1A2, is a member of the cytochrome P450 mixed-function oxidase system. It is involved in the metabolism of xenobiotics in the body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.

CYP1A2 is mainly confined to the liver and expressed at a very low level in extrahepatic tissue.

CYP2A6 and CYP1A2 were found to be the most important P450 enzymes involved in 1'-hydroxylation of estragole (methyl chavicol).[19]


O-Demethylation Reactions

CYP2C9 and CYP1A2 were shown to O-demethylate S-naproxen to O-desmethylnaproxen in human liver microsomes in vitro.[11]

Naproxen CYP1A2 O-Desmethylnaproxen
Naproxen.png —-> O-Desmethylnaproxen.png

CYP1A2 Inhibitors

Potent Inhibitors Strength Dosage Verified in Humans
Apigenin (found in parsley, carrots, parsnips, celery, German chamomile flowers) ? ? ?
Caffeine 142% increase in substrate 600 mg (taken with 6 mg melatonin as the substrate) Yes[17](needs further verification)
Capsaicin (found in cayenne pepper, habanero peppers, etc.) ? ? ?
Cayenne pepper ? Possibly 500-800 mg (needs more testing) ?
Chrysin (from Passiflora caerulea) ? ? ?
Chamazulene (from German chamomile EO) 50 % inhibition IC50 = 4.41 µM[7] ?
Cis-spiroether (from German chamomile EO) 50 % inhibition IC50 = 2.01 µM[7] ?
Common sage ? ? ?
Cryptotanshinone ? ? ?
Furafylline 50% Inhibition IC50=0.79 µM[9] ?
Galangin ? ? ?
German chamomile EO ? 5-10 drops orally, 1-2 drops topically (needs confirmation) ?
German chamomile flowers ? 5-10 grams grams orally (needs confirmation) ?
Kaempferol ? ? ?
Kava ? ? Yes[14]
Myricetin ? ? ?
Parsley leaf ? possibly 200-500 mg (needs confirmation) ?
Resveratrol1 50% Inhibition IC50=0.79 µM[9] ?
Rutaecarpine (from Evodia rutaecarpa) ? ? ?
Saint John’s Wort (high dose) ? ? ?
Salvia miltiorrhiza (danshen) ? ? ?
Star fruit juice ? ? ?
Tangeretin ? ? ?
Tanshinone I ? ? ?
Tanshinone IIA ? ? ?
Thymoquinone (in Nigella sativa)[8] ? ? ?
Trans-spiroether (from German chamomile EO) 50 % inhibition IC50 = 0.47 µM[7] ?
Moderate Inhibitors Strength Dosage Verified in Humans
Curcumin 28.6% inhibition 1000 mg Yes[5]
Daidzein 40.47% increase in substrates 200 mg twice daily for 10 days Yes[13]
Echinacea purpurea ? 400 mg 4 times a day Yes[3]
Quercetin 10.4% inhibition[15] 500 mg Yes[15][16]
Turmeric (contains curcumin [5]) Moderate ? Yes
Weak Inhibitors Strength Dosage Verified in Humans
White grapefruit juice [4] Weak ? Yes
Inhibitors (potency unknown) Strength Dosage Verified in Humans
Piperine ? ? Inconclusive[1]
Pomegranate juice [6] ? ? In mice only
Vanillin [18] ? ? ?

CYP1A2 Inducers

Moderate Inducers Strength Dosage Verified in Humans
Rifampicin [2] ? 500 mg Yes
Inducers (potency unspecified) Strength Dosage Verified in Humans
Beta-naphthoflavone ? ? ?
Caffeine (inhibits[17] then induces)2 ? ? ?
Methyl eugenol ? ? ?
Tobacco smoking ? ? ?
Myristicin ? ? ?
Piperine ? ? Inconclusive[10]
Pueraria lobata (Kudzu) ? ? ?
Resveratrol ? ? Yes[12]

Bibliography
1. Shu-Feng Zhou, Zhi-Wei Zhou, Chun-Guang Li, Xiao Chen, Xiyong Yu, Charlie
Changli Xue, and Adrian Herington Identification of drugs that interact with herbs in drug development; Drug Discovery Today 12(15-16):pp. 664-673; Adrian (2007) (Download Attached PDF Document)
2. Cytochrome P450 Induction by Rifampicin in Healthy Subjects: Determination Using the Karolinska Cocktail and the Endogenous CYP3A4 Marker 4β-Hydroxycholesterol
KP Kanebratt, U Diczfalusy, T Bäckström, E Sparve, E Bredberg, Y Böttiger, TB Andersson and L Bertilsson; Doi:10.1038/clpt.2008.132; Clinical Pharmacology & Therapeutics, Volume 84 Number 5, November 2008
3. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo;
Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD; Clin Pharmacol Ther. 2004 Jan;75(1):89-100; Department of Medicine, Indiana University School of Medicine, Indianapolis, 46202-2879, USA; PubMed PMID: 14749695
4. Br J Clin Pharmacol. 1993 Apr;35(4):431-6;
Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man' Fuhr U, Klittich K, Staib AH; Department of Clinical Pharmacology, University Hospital Frankfurt/Main, Germany; PubMed PMID: 8485024
5. Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers;
Ann Pharmacother. 2010 Jun;44(6):1038-45. doi: 10.1345/aph.1M533. Epub 2010 May 18; Chen Y, Liu WH, Chen BL, Fan L, Han Y, Wang G, Hu DL, Tan ZR, Zhou G, Cao S, Zhou HH; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China. PubMed PMID: 20484172
6. J Med Food. 2007 Dec;10(4):643-9.
Pomegranate juice effects on cytochrome P450S expression: in vivo studies. Faria A, Monteiro R, Azevedo I, Calhau C; Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal. PubMed PMID: 18158835
7. Inhibitory effects of the essential oil of chamomile (Matricaria recutita L.) and its major constituents on human cytochrome P450 enzymes.
Ganzera M, Schneider P, Stuppner H. PubMed PMID: 16137701
8. Modulation of hepatic drug metabolizing enzymes by dietary doses of thymoquinone in female New Zealand White rabbits.
Elbarbry F, Ragheb A, Marfleet T, Shoker A. PubMed PMID: 22422469
9. Cell-based high-throughput bioassays to assess induction and inhibition of CYP1A enzymes.
Yueh MF, Kawahara M, Raucy J. PubMed PMID: 10448061
10. Effect of Piperine on Caffeine Salivary Concentration in Healthy Volunteers
A. Gholampour (MD), M. Hashemi (BSc), M.M. Rezaee (MD), M.R. Shiran (Pharm D, PhD), A.A. Moghadamnia (Pharm D, PhD); J Babol Univ Med Sci; 15(4); Jul 2013; pp: 12-21
11. Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen.
Miners JO, Coulter S, Tukey RH, Veronese ME, Birkett DJ.; Biochem Pharmacol. 1996 Apr 26;51(8):1003-8.; PMID: 8866821
12.
Resveratrol Modulates Drug- and Carcinogen-Metabolizing Enzymes in a Healthy Volunteer Study H-H. Sherry Chow, Linda L. Garland, Chiu-Hsieh Hsu, Donna R. Vining, Wade M. Chew, Jessica A. Miller, Marjorie Perloff, James A. Crowell and David S. Alberts; DOI: 10.1158/1940-6207.CAPR-09-0155 Published September 2010; PubMed PMCID: PMC2933312; NIHMSID: NIHMS207754
13. Effect of daidzein on CYP1A2 activity and pharmacokinetics of theophylline in healthy volunteers.
Peng WX, Li HD, Zhou HH.; Eur J Clin Pharmacol. 2003 Jul;59(3):237-41. Epub 2003 May 17.; PMID: 12756512; DOI: 10.1007/s00228-003-0596-0
14. Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: Protective effect against environmental carcinogens?
Russmann S, Lauterburg BH, Barguil Y, Choblet E, Cabalion P, Rentsch K, Wenk M.; Clin Pharmacol Ther. 2005 May;77(5):453-4.; PMID: 15900292; DOI: 10.1016/j.clpt.2005.01.021
15. Simultaneous action of the flavonoid quercetin on cytochrome P450 (CYP) 1A2, CYP2A6, N-acetyltransferase and xanthine oxidase activity in healthy volunteers.
Chen Y, Xiao P, Ou-Yang DS, Fan L, Guo D, Wang YN, Han Y, Tu JH, Zhou G, Huang YF, Zhou HH. PubMed PMID: 19215233
16. Quercetin Significantly Inhibits the Metabolism of Caffeine, a Substrate of Cytochrome P450 1A2 Unrelated to CYP1A2*1C  (−2964G>A) and *1F (734C>A) Gene Polymorphisms.
Jian Xiao, Wei-Hua Huang, Jing-Bo Peng, Zhi-Rong Tan, Dong-Sheng Ou-Yang, Dong-Li Hu, Wei Zhang, Yao Chen PubMed PMCID: PMC4082882
17. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity.
Härtter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine K. PubMed PMID: 14616429
18. Effect of vanillin and ethyl vanillin on cytochrome P450 activity in vitro and in vivo.
Chen XM, Wei M, Zhang HM, Luo CH, Chen YK, Chen Y. PMID: 22450566
19. Human cytochrome p450 enzyme specificity for the bioactivation of estragole and related alkenylbenzenes.
Jeurissen SM, Punt A, Boersma MG, Bogaards JJ, Fiamegos YC, Schilter B, van Bladeren PJ, Cnubben NH, Rietjens IM. PMID: 17407329

If an inducer or inhibitor is present on this page and reliable human in vivo studies are available but not shown on this page please leave a comment about it using the Discuss link at the bottom of this page so we can update the inhibitor's data.

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