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Review Articles

Bioactivation of herbal constituents: mechanisms and toxicological relevance

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Pages 453-497 | Received 05 Jun 2019, Accepted 08 Aug 2019, Published online: 26 Aug 2019

References

  • Ahmad I, Shukla S, Kumar A, Singh BK, Kumar V, Chauhan AK, Singh D, Pandey HP, Singh C. 2013. Biochemical and molecular mechanisms of N-acetyl cysteine and silymarin-mediated protection against maneb- and paraquat-induced hepatotoxicity in rats. Chem Biol Interact. 201(1–3):9–18.
  • Alam F, Khan GN, Asad M. 2018. Psoralea corylifolia L: ethnobotanical, biological, and chemical aspects: a review. Phytother Res. 32(4):597–615.
  • Alhusainy W, Paini A, van den Berg JH, Punt A, Scholz G, Schilter B, van Bladeren PJ, Taylor S, Adams TB, Rietjens IM. 2013. In vivo validation and physiologically based biokinetic modeling of the inhibition of SULT-mediated estragole DNA adduct formation in the liver of male Sprague-Dawley rats by the basil flavonoid nevadensin. Mol Nutr Food Res. 57(11):1969–1978.
  • Alhusainy W, Williams GM, Jeffrey AM, Iatropoulos MJ, Taylor S, Adams TB, Rietjens IM. 2014. The natural basil flavonoid nevadensin protects against a methyleugenol-induced marker of hepatocarcinogenicity in male F344 rat. Food Chem Toxicol. 74:28–34.
  • Ambrosone CB, McCann SE, Freudenheim JL, Marshall JR, Zhang Y, Shields PG. 2004. Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J Nutr. 134(5):1134–1138.
  • Aneja R, Katyal A, Chandra R. 2004. Modulatory influence of noscapine on the ethanol-altered hepatic biotransformation system enzymes, glutathione content and lipid peroxidation in vivo in rats. Eur J Drug Metab Pharmacokinet. 29(3):157–162.
  • Anthony A, Caldwell J, Hutt AJ, Smith RL. 1987. Metabolism of estragole in rat and mouse and influence of dose size on excretion of the proximate carcinogen 1'-hydroxyestragole. Food Chem Toxicol. 25(11):799–806.
  • Arlt VM, Ferluga D, Stiborova M, Pfohl-Leszkowicz A, Vukelic M, Ceovic S, Schmeiser HH, Cosyns JP. 2002. Is aristolochic acid a risk factor for Balkan endemic nephropathy-associated urothelial cancer? Int J Cancer. 101(5):500–502.
  • Arlt VM, Stiborova M, Schmeiser HH. 2002. Aristolochic acid as a probable human cancer hazard in herbal remedies: a review. Mutagenesis. 17(4):265–277.
  • Arlt VM, Stiborová M, Vom Brocke J, Simões ML, Lord GM, Nortier JL, Hollstein M, Phillips DH, Schmeiser HH. 2007. Aristolochic acid mutagenesis: molecular clues to the aetiology of Balkan endemic nephropathy-associated urothelial cancer. Carcinogenesis. 28(11):2253–2261.
  • Asher GN, Corbett AH, Hawke RL. 2017. Common herbal dietary supplement-drug interactions. Am Fam Physician. 96(2):101–107.
  • Awad HM, Boersma MG, Boeren S, Van Bladeren PJ, Vervoort J, Rietjens IM. 2003. Quenching of quercetin quinone/quinone methides by different thiolate scavengers: stability and reversibility of conjugate formation. Chem Res Toxicol. 16(7):822–831.
  • Awad HM, Boersma MG, Vervoort J, Rietjens IM. 2000. Peroxidase-catalyzed formation of quercetin quinone methide-glutathione adducts. Arch Biochem Biophys. 378(2):224–233.
  • Bailey DG, Spence JD, Edgar B, Bayliff CD, Arnold JM. 1989. Ethanol enhances the hemodynamic effects of felodipine. Clin Invest Med. 12(6):357–362.
  • Baillie TA. 2008. Metabolism and toxicity of drugs. Two decades of progress in industrial drug metabolism. Chem Res Toxicol. 21(1):129–137.
  • Baillie TA. 2016. Targeted covalent inhibitors for drug design. Angew Chem Int Ed Engl. 55(43):13408–13421.
  • Baudoux TE, Pozdzik AA, Arlt VM, De Prez EG, Antoine MH, Quellard N, Goujon JM, Nortier JL. 2012. Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid nephropathy. Kidney Int. 82(10):1105–1113.
  • Becker MW, Lourençone EMS, De Mello AF, Branco A, Filho EMR, Blatt CR, Mallmann CA, Schneider M, Caregnato RCA, Blatt CR. 2019. Liver transplantation and the use of KAVA: case report. Phytomedicine. 56:21–26.
  • Beekman AC, Woerdenbag HJ, van Uden W, Pras N, Konings AW, Wikström HV, Schmidt TJ. 1997. Structure-cytotoxicity relationships of some helenanolide-type sesquiterpene lactones. J Nat Prod. 60(3):252–257.
  • Bhagya N, Chandrashekar KR. 2016. Tetrandrine-A molecule of wide bioactivity. Phytochemistry. 125:5–13.
  • Billinsky JL, Marcoux MR, Krol ES. 2007. Oxidation of the lignan nordihydroguaiaretic acid. Chem Res Toxicol. 20(9):1352–1358.
  • Bley K, Boorman G, Mohammad B, McKenzie D, Babbar S. 2012. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 40(6):847–873.
  • Bodi D, Ronczka S, Gottschalk C, Behr N, Skibba A, Wagner M, Lahrssen-Wiederholt M, Preiss-Weigert A, These A. 2014. Determination of pyrrolizidine alkaloids in tea, herbal drugs and honey. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 31(11):1886–1895.
  • Boelsterli UA, Ho HK, Zhou S, Leow KY. 2006. Bioactivation and hepatotoxicity of nitroaromatic drugs. Curr Drug Metab. 7(7):715–727.
  • Bolleddula J, Chowdhury SK. 2015. Carbon-carbon bond cleavage and formation reactions in drug metabolism and the role of metabolic enzymes. Drug Metab Rev. 47(4):534–557.
  • Bolton JL, Acay NM, Vukomanovic V. 1994. Evidence that 4-allyl-o-quinones spontaneously rearrange to their more electrophilic quinone methides: potential bioactivation mechanism for the hepatocarcinogen safrole. Chem Res Toxicol. 7(3):443–450.
  • Bolton JL, Dunlap T. 2017. Formation and biological targets of quinones: cytotoxic versus cytoprotective effects. Chem Res Toxicol. 30(1):13–37.
  • Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ. 2000. Role of quinones in toxicology. Chem Res Toxicol. 13(3):135–160.
  • Born SL, Caudill D, Fliter KL, Purdon MP. 2002. Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. Drug Metab Dispos. 30(5):483–487.
  • Bounda GA, Feng Y. 2015. Review of clinical studies of Polygonum multiflorum thunb. and its isolated bioactive compounds. Pharmacognosy Res. 7(3):225–236.
  • Bourdi M, Tinel M, Beaune PH, Pessayre D. 1994. Interactions of dihydralazine with cytochromes P4501A: a possible explanation for the appearance of anti-cytochrome P4501A2 autoantibodies. Mol Pharmacol. 45(6):1287–1295.
  • Brantley SJ, Argikar AA, Lin YS, Nagar S, Paine MF. 2014. Herb-drug interactions: challenges and opportunities for improved predictions. Drug Metab Dispos. 42(3):301–317.
  • Bristol DW. 2011. NTP 3-month toxicity studies of estragole (CAS No. 140-67-0) administered by gavage to F344/N rats and B6C3 mice. National Toxicology Program Toxicity Report Series Number 82. NIH Publication No. 08-5966. pp. 1–111.
  • Brown KK, Blaikie FH, Smith RA, Tyndall JD, Lue H, Bernhagen J, Winterbourn CC, Hampton MB. 2009. Direct modification of the proinflammatory cytokine macrophage migration inhibitory factor by dietary isothiocyanates. J Biol Chem. 284(47):32425–32433.
  • Buiatti E, Palli D, Decarli A, Amadori D, Avellini C, Bianchi S, Biserni R, Cipriani F, Cocco P, Giacosa A. 1989. A case-control study of gastric cancer and diet in Italy. Int J Cancer. 44(4):611–616.
  • Cai Q, Wei J, Zhao W, Shi S, Zhang Y, Wei R, Zhang Y, Li W, Wang Q. 2014. Toxicity of Evodiae fructus on rat liver mitochondria: the role of oxidative stress and mitochondrial permeability transition. Molecules. 19(12):21168–21182.
  • Cai W, Guan Y, Zhou Y, Wang Y, Ji H, Liu Z. 2017. Detection and characterization of the metabolites of rutaecarpine in rats based on ultra-high-performance liquid chromatography with linear ion trap-Orbitrap mass spectrometer. Pharm Biol. 55(1):294–298.
  • Cai Y, Bennett D, Nair RV, Ceska O, Ashwood-Smith MJ, DiGiovanni J. 1993. Inhibition and inactivation of murine hepatic ethoxy- and pentoxyresorufin O-dealkylase by naturally occurring coumarins. Chem Res Toxicol. 6(6):872–879.
  • Caldwell J, Sutton JD. 1988. Influence of dose size on the disposition of trans-[methoxy-14C] anethole in human volunteers. Food Chem Toxicol. 26(2):87–91.
  • Cao J, Zheng L, Ji L, Lu D, Peng Y, Zheng J. 2015. Mechanism-based inactivation of cytochrome P450 2B6 by isoimperatorin. Chem Biol Interact. 226:23–29.
  • Cartus AT, Merz KH, Schrenk D. 2011. Metabolism of methylisoeugenol in liver microsomes of human, rat, and bovine origin. Drug Metab Dispos. 39(9):1727–1733.
  • Chan W, Cui L, Xu G, Cai Z. 2006. Study of the phase I and phase II metabolism of nephrotoxin aristolochic acid by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 20(11):1755–1760.
  • Chan W, Luo HB, Zheng Y, Cheng YK, Cai Z. 2007. Investigation of the metabolism and reductive activation of carcinogenic aristolochic acids in rats. Drug Metab Dispos. 35(6):866–874.
  • Chan WK, Delucchi AB. 2000. Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4. Life Sci. 67(25):3103–3112.
  • Chang SY, Weber EJ, Sidorenko VS, Chapron A, Yeung CK, Gao C, Mao Q, Shen D, Wang J, Rosenquist TA, et al. 2017. Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity. JCI Insight. 2(22):95978.
  • Chang TK, Chen J, Lee WB. 2001. Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J Pharmacol Exp Ther. 299(3):874–882.
  • Chatterjee P, Franklin MR. 2003. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos. 31(11):1391–1397.
  • Chen C, Pung D, Leong V, Hebbar V, Shen G, Nair S, Li W, Kong AN. 2004. Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: effect of chemical structure and stress signals. Free Radic Biol Med. 37(10):1578–1590.
  • Chen M, Gong L, Qi X, Xing G, Luan Y, Wu Y, Xiao Y, Yao J, Li Y, Xue X, et al. 2011a. Inhibition of renal NQO1 activity by dicoumarol suppresses nitroreduction of aristolochic acid I and attenuates its nephrotoxicity. Toxicol Sci. 122(2):288–296.
  • Chen M, Li L, Zhong D, Shen S, Zheng J, Chen X. 2016. 9-Glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine is the major pyrrolic glutathione conjugate of retronecine-type pyrrolizidine alkaloids in liver microsomes and in rats. Chem Res Toxicol. 29(2):180–189.
  • Chen W, Shockcor JP, Tonge R, Hunter A, Gartner C, Nelson SD. 1999. Protein and nonprotein cysteinyl thiol modification by N-acetyl-p-benzoquinone imine via a novel ipso adduct. Biochemistry. 38(25):8159–8166.
  • Chen XW, Serag ES, Sneed KB, Zhou SF. 2011b. Herbal bioactivation, molecular targets and the toxicity relevance. Chem Biol Interact. 192(3):161–176.
  • Chen Y, Yu J, Wang 1, Li H, Mao X, Peng Y, Zheng J. 2018. Characterization of glutathione conjugates derived from reactive metabolites of seven silymarin isomers. Xenobiotica. 29:1–13.
  • Cheung WI, Tse ML, Ngan T, Lin J, Lee WK, Poon WT, Mak TW, Leung VK, Chau TN. 2009. Liver injury associated with the use of Fructus Psoraleae (Bol-gol-zhee or Bu-gu-zhi) and its related proprietary medicine. Clin Toxicol (Phila). 47(7):683–685.
  • Chi M, Peng Y, Zheng J. 2016. Characterization of glutathione conjugates derived from reactive metabolites of bakuchiol. Chem Biol Interact. 244:178–186.
  • Cho T, Uetrecht J. 2017. How reactive metabolites induce an immune response that sometimes leads to an idiosyncratic drug reaction. Chem Res Toxicol. 30(1):295–314.
  • Choi JM, Oh SJ, Lee JY, Jeon JS, Ryu CS, Kim YM, Lee K, Kim SK. 2015. Prediction of drug-induced liver injury in HepG2 cells cultured with human liver microsomes. Chem Res Toxicol. 28(5):872–885.
  • Chojkier M. 2003. Hepatic sinusoidal-obstruction syndrome: toxicity of pyrrolizidine alkaloids. J Hepatol. 39(3):437–446.
  • Chung FL, Wang MY, Hecht SS. 1985. Effects of dietary indoles and isothiocyanates on N-nitrosodimethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone alpha-hydroxylation and DNA methylation in rat liver. Carcinogenesis. 6(4):539–543.
  • Cohen SM, Heywood E, Pillai A, Ahn J. 2012. Hepatotoxicity associated with the use of White Flood, a nutritional supplement. Pract Gastroenterol. 10:45–48.
  • Conaway CC, Yang YM, Chung FL. 2002. Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr Drug Metab. 3(3):233–255.
  • Cooper RA, Huxtable RJ. 1999. The relationship between reactivity of metabolites of pyrrolizidine alkaloids and extrahepatic toxicity. Proc West Pharmacol Soc. 42:13–16.
  • Cote CS, Kor C, Cohen J, Auclair K. 2004. Composition and biological activity of traditional and commercial kava extracts. Biochem Biophys Res Commun. 322(1):147–152.
  • Dalvie D, Kalgutkar AS, Chen W. 2015. Practical approaches to resolving reactive metabolite liabilities in early discovery. Drug Metab Rev. 47(1):56–70.
  • Danan G, Teschke R. 2018. Drug-induced liver injury: why is the Roussel Uclaf Causality Assessment Method (RUCAM) still used 25 years after its launch? Drug Saf. 41(8):735–743.
  • De Berardinis V, Moulis C, Maurice M, Beaune P, Pessayre D, Pompon D, Loeper J. 2000. Human microsomal epoxide hydrolase is the target of germander-induced autoantibodies on the surface of human hepatocytes. Mol Pharmacol. 58(3):542–551.
  • de Boer YS, Sherker AH. 2017. Herbal and dietary supplement-induced liver injury. Clin Liver Dis. 21(1):135–149.
  • Debelle FD, Vanherweghem JL, Nortier JL. 2008. Aristolochic acid nephropathy: a worldwide problem. Kidney Int. 74(2):158–169.
  • Delaveau P. 1986. La Germandree petit-chene (Wild germander). Actual Pharm. 238:34–39.
  • Deng Y, Fu Y, Xu S, Wang P, Yang N, Li C, Yu Q. 2018. Detection and structural characterization of nucleophiles trapped reactive metabolites of Limonin using liquid chromatography-mass spectrometry. J Anal Methods Chem. 2018:1.
  • Dietary Supplement and Nonprescription Drug Consumer Protection Act 2006. Public Law 109-462, 120 STAT. 3469. https://www.govinfo.gov/app/details/PLAW-109publ462.
  • Ding Y, Paonessa JD, Randall KL, Argoti D, Chen L, Vouros P, Zhang Y. 2010. Sulforaphane inhibits 4-aminobiphenyl-induced DNA damage in bladder cells and tissues. Carcinogenesis. 31(11):1999–2003.
  • Dong H, Slain D, Cheng J, Ma W, Liang W. 2014. Eighteen cases of liver injury following ingestion of Polygonum multiflorum. Complement Ther Med. 22(1):70–74.
  • Dong X, Ni B, Fu J, Yin X, You L, Leng X, Liang X, Ni J. 2018. Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspase-dependent pathway. Oncol Rep. 40(4):1985–1993.
  • Drogosz J, Janecka A. 2019. Helenalin - a sesquiterpene lactone with multidirectional activity. Curr Drug Targets. 20(4):444–452.
  • Druckova A, Marnett LJ. 2006. Characterization of the amino acid adducts of the enedial derivative of teucrin A. Chem Res Toxicol. 19(10):1330–1340.
  • Druckova A, Mernaugh RL, Ham AJ, Marnett LJ. 2007. Identification of the protein targets of the reactive metabolite of teucrin A in vivo in the rat. Chem Res Toxicol. 20(10):1393–1408.
  • Du WY, Xiao Y, Yao JJ, Hao Z, Zhao YB. 2018. Chlorogenic acid in the oxidative stress injury triggered by Shuang-Huang-Lian injection. Exp Ther Med. 16(4):2901–2908.
  • Dueker SR, Lamé MW, Morin D, Wilson DW, Segall HJ. 1992. Guinea pig and rat hepatic microsomal metabolism of monocrotaline. Drug Metab Dispos. 20(2):275–280.
  • Dunn IS, Liberato DJ, Castagnoli N, Byers VS. 1982. Contact sensitivity to urushiol: role of covalent bond formation. Cell Immunol. 74(2):220–233.
  • Dunnick JK, Hailey JR. 1992. Toxicity and carcinogenicity studies of quercetin, a natural component of foods. Fundam Appl Toxicol. 19(3):423–431.
  • Efferth T, Kaina B. 2011. Toxicities by herbal medicines with emphasis to traditional Chinese medicine. Curr Drug Metab. 12(10):989–996.
  • Empey DW, Laitinen LA, Young GA, Bye CE, Hughes D. 1979. Comparison of the antitussive effects of codeine phosphate 20 mg, dextromethorphan 30 mg and noscapine 30 mg using citric acid-induced cough in normal subjects. Eur J Clin Pharmacol. 16(6):393–397.
  • Espinoza JL, Kurokawa Y, Takami A. 2019. Rationale for assessing the therapeutic potential of resveratrol in hematological malignancies. Blood Rev. 33:43–52.
  • Fan YJ, Rong Y, Li PF, Dong WL, Zhang DY, Zhang L, Cui MJ. 2013. Genistein protection against acetaminophen-induced liver injury via its potential impact on the activation of UDP-glucuronosyltransferase and antioxidant enzymes. Food Chem Toxicol. 55:172–181.
  • Fang ZZ, Krausz KW, Li F, Cheng J, Tanaka N, Gonzalez FJ. 2012. Metabolic map and bioactivation of the anti-tumour drug noscapine. Br J Pharmacol. 167(6):1271–1286.
  • Fang ZZ, Zhang YY, Ge GB, Huo H, Liang SC, Yang L. 2010. Time-dependent inhibition (TDI) of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine-warfarin interaction. Br J Clin Pharmacol. 69(2):193–199.
  • Federico A, Dallio M, Loguercio C. 2017. SilymarinSilybin and chronic liver disease: a marriage of many years. Molecules. 22(2):191.
  • Felter SP, Vassallo JD, Carlton BD, Daston GP. 2006. A safety assessment of coumarin taking into account species-specificity of toxicokinetics. Food Chem Toxicol. 44(4):462–475.
  • Feng C, Xie X, Wu M, Li C, Gao M, Liu M, Qi X, Ren J. 2013. Tanshinone I protects mice from aristolochic acid I-induced kidney injury by induction of CYP1A. Environ Toxicol Pharmacol. 36(3):850–857.
  • Fischer IU, von Unruh GE, Dengler HJ. 1990. The metabolism of eugenol in man. Xenobiotica. 20(2):209–222.
  • Forkert PG, Premdas PD, Bowers RJ. 2000. Epoxide formation from diallyl sulfone is associated with CYP2E1 inactivation in murine and human lungs. Am J Respir Cell Mol Biol. 23(5):687–695.
  • Frémont L. 2000. Biological effects of resveratrol. Life Sci. 66(8):663–673.
  • Fu PP, Chou MW, Churchwell M, Wang Y, Zhao Y, Xia Q, Gamboa da Costa G, Marques MM, Beland FA, Doerge DR. 2010. High-performance liquid chromatography electrospray ionization tandem mass spectrometry for the detection and quantitation of pyrrolizidine alkaloid-derived DNA adducts in vitro and in vivo. Chem Res Toxicol. 23(3):637–652.
  • Fu PP, Xia Q, Lin G, Chou MW. 2004. Pyrrolizidine alkaloids-genotoxicity, metabolism enzymes, metabolic activation, and mechanisms. Drug Metab Rev. 36(1):1–55.
  • Fu PP. 2017. Pyrrolizidine alkaloids: metabolic activation pathways leading to liver tumor initiation. Chem Res Toxicol. 30(1):81–93.
  • Gao Y, Hou R, Han Y, Fei Q, Cai R, Qi Y. 2018. Shuang-Huang-Lian injection induces an immediate hypersensitivity reaction via C5a but not IgE. Sci Rep. 8(1):3572.
  • Glatt H. 2000. Sulfotransferases in the bioactivation of xenobiotics. Chem Biol Interact. 129(1–2):141–170.
  • Gordon P, Khojasteh SC. 2015. A decades-long investigation of acute metabolism-based hepatotoxicity by herbal constituents: a case study of pennyroyal oil. Drug Metab Rev. 47(1):12–20.
  • Gordon WP, Forte AJ, McMurtry RJ, Gal J, Nelson SD. 1982. Hepatotoxicity and pulmonary toxicity of pennyroyal oil and its constituent terpenes in the mouse. Toxicol Appl Pharmacol. 65(3):413–424.
  • Gordon WP, Huitric AC, Seth CL, McClanahan RH, Nelson SD. 1987. The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab Dispos. 15(5):589–594.
  • Grice HC, Becking G, Goodman T. 1968. Toxic properties of nordihydroguaiaretic acid. Food Cosmet Toxicol. 6(2):155–161.
  • Grillo MP. 2015. Detecting reactive drug metabolites for reducing the potential for drug toxicity. Expert Opin Drug Metab Toxicol. 11(8):1281–1302.
  • Grimm SW, Einolf HJ, Hall SD, He K, Lim HK, Ling KH, Lu C, Nomeir AA, Seibert E, Skordos KW, et al. 2009. The conduct of in vitro studies to address time-dependent inhibition of drug-metabolizing enzymes: a perspective of the pharmaceutical research and manufacturers of America. Drug Metab Dispos. 37(7):1355–1370.
  • Grollman AP, Shibutani S, Moriya M, Miller F, Wu L, Moll U, Suzuki N, Fernandes A, Rosenquist T, Medverec Z, et al. 2007. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci Usa . 104(29):12129–12134.
  • Guenthner TM, Luo G. 2001. Investigation of the role of the 2',3'-epoxidation pathway in the bioactivation and genotoxicity of dietary allylbenzene analogs. Toxicology. 160(1–3):47–58.
  • Gunby P. 1979. Plant known for centuries still causes problems today. JAMA. 241(21):2246–2247.
  • Guo LQ, Fukuda K, Ohta T, Yamazoe Y. 2000. Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metab Dispos. 28(7):766–771.
  • Gupta PK, Barone G, Gurley BJ, Fifer EK, Hendrickson HP. 2015. Hydrastine pharmacokinetics and metabolism after a single oral dose of goldenseal (Hydrastis canadensis) to humans. Drug Metab Dispos. 43(4):534–552.
  • Gurley BJ, Swain A, Hubbard MA, Hartsfield F, Thaden J, Williams DK, Gentry WB, Tong Y. 2008. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo. Clin Pharmacol Ther. 83(1):61–69.
  • Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK. 2008. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res. 52(7):755–763.
  • Hajirahimkhan A, Dietz BM, Bolton JL. 2013. Botanical modulation of menopausal symptoms: mechanisms of action? Planta Med. 79(7):538–553.
  • Han XD, Zhang YY, Wang KL, Huang YP, Yang ZB, Liu Z. 2017. The involvement of Nrf2 in the protective effects of (-)-Epigallocatechin-3-gallate (EGCG) on NaAsO2-induced hepatotoxicity. Oncotarget. 8(39):65302–65312.
  • Hasheminejad G, Caldwell J. 1994. Genotoxicity of the alkenylbenzenes alpha- and beta-asarone, myristicin and elimicin as determined by the UDS assay in cultured rat hepatocytes. Food Chem Toxicol. 32(3):223–231.
  • Hashimoto K, Zaitseva IN, Bonala R, Attaluri S, Ozga K, Iden CR, Johnson F, Moriya M, Grollman AP, Sidorenko VS. 2016. Sulfotransferase-1A1-dependent bioactivation of aristolochic acid I and N-hydroxyaristolactam I in human cells. Carcinogenesis. 37(7):647–655.
  • He K, Iyer KR, Hayes RN, Sinz MW, Woolf TF, Hollenberg PF. 1998. Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol. 11(4):252–259.
  • Hecht SS. 2000. Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev. 32(3-4):395–411.
  • Hernández-Damián J, Andérica-Romero AC, Pedraza-Chaverri J. 2014. Paradoxical cellular effects and biological role of the multifaceted compound nordihydroguaiaretic acid. Arch Pharm (Weinheim). 347(10):685–697.
  • Hincks JR, Kim HY, Segall HJ, Molyneux RJ, Stermitz FR, Coulombe RA, Jr. 1991. DNA cross-linking in mammalian cells by pyrrolizidine alkaloids: structure-activity relationships. Toxicol Appl Pharmacol. 111(1):90–98.
  • Hollenberg PF, Kent UM, Bumpus NN. 2008. Mechanism-based inactivation of human cytochromes p450s: experimental characterization, reactive intermediates, and clinical implications. Chem Res Toxicol. 21(1):189–205.
  • Hong F, Freeman ML, Liebler DC. 2005. Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem Res Toxicol. 18(12):1917–1926.
  • Howes AJ, Chan VS, Caldwell J. 1990. Structure-specificity of the genotoxicity of some naturally occurring alkenylbenzenes determined by the unscheduled DNA synthesis assay in rat hepatocytes. Food Chem Toxicol. 28(8):537–542.
  • Hu C, Liang Q, Tang X, Wang Y, Ma Z, Xiao C, Tan H, Gao Y, Huang X. 2015. In vivo metabolite identification of bakuchiol in rats by UPLC/ESI-PDA-QTOF-MS. Fitoterapia. 106:129–134.
  • Hu X, Li D, Chu C, Li X, Wang X, Jia Y, Hua H, Xu F. 2018a. Antiproliferative effects of alkaloid evodiamine and its derivatives. IJMS. 19(11):3403.
  • Hu XJ, Zhang YB, Zhao ZJ, Zhang L, Wang Q, Yang XW. 2018b. Metabolic detoxification of bakuchiol is mediated by oxidation of CYP 450s in liver microsomes. Food Chem Toxicol. 111:385–392.
  • Huang K, Huang L, van Breemen RB. 2015. Detection of reactive metabolites using isotope-labeled glutathione trapping and simultaneous neutral loss and precursor ion scanning with ultra-high-pressure liquid chromatography triple quadruple mass spectrometry. Anal Chem. 87(7):3646–3654.
  • Huang Q, Lawson TA, Chung FL, Morris CR, Mervish SS. 1993. Inhibition by phenylethyl and phenylhexyl isothiocyanate of metabolism of and DNA methylation by N-nitrosomethylamylamine in rats. Carcinogenesis. 14(4):749–754.
  • Huang YT, Hong CY. 1998. Tetrandrine. Cardiovasc Drug Reviews. 19:1–15.
  • International Agency for Research on Cancer (IARC). 1976. Safrole, isosafrole and dihydrosafrole. In Some Naturally Occurring Substances, Vol. 10, pp. 231–244. International Agency for Research on Cancer, Lyon, France. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans.
  • International Programme on Chemical Safety (IPCS). 1989. Pyrrolizidine Alkaloids Health and Safety Guide. Health and Safety Criteria Guide 26. WHO, Geneva.
  • Ioannides C, Konsue N. 2015. A principal mechanism for the cancer chemopreventive activity of phenethyl isothiocyanate is modulation of carcinogen metabolism. Drug Metab Rev. 47(3):356–373.
  • Ishii T, Mori T, Tanaka T, Mizuno D, Yamaji R, Kumazawa S, Nakayama T, Akagawa M. 2008. Covalent modification of proteins by green tea polyphenol (-)-epigallocatechin-3-gallate through autoxidation. Free Radic Biol Med. 45(10):1384–1394.
  • Iwata H, Tezuka Y, Kadota S, Hiratsuka A, Watabe T. 2005. Mechanism-based inactivation of human liver microsomal CYP3A4 by rutaecarpine and limonin from Evodia fruit extract. Drug Metab Pharmacokinet. 20(1):34–45.
  • Iwata H, Tezuka Y, Kadota S, Hiratsuka A, Watabe T. 2004. Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos. 32(12):1351–1358.
  • Iyer LV, Ho MN, Shinn WM, Bradford WW, Tanga MJ, Nath SS, Green CE. 2003. Glucuronidation of 1'-hydroxyestragole (1'-HE) by human UDP-glucuronosyltransferases UGT2B7 and UGT1A9. Toxicol Sci. 73(1):36–43.
  • Jadot I, Declèves AE, Nortier J, Caron N. 2017. An integrated view of aristolochic acid nephropathy: update of the literature. IJMS. 18(2):297.
  • Jeon TW1, Jin CH, Lee SK, Jun IH, Kim GH, Lee DJ, Jeong HG, Lee KB, Jahng Y, Jeong TC. 2006. Immunosuppressive effects of rutaecarpine in female BALB/c mice. Toxicol Lett. 164(2):155–166.
  • Jeong H, Kim S, Lee J, Park JY, Zhou W, Liu X, Kim SD, Song YS, Jang CY, Oh SR, et al. 2017. Characterization of phase I and phase II hepatic metabolism and reactive intermediates of larrea nitida Cav. and its lignan compounds. Phytother Res. 31(1):140–151.
  • Jeurissen SM, Punt A, Boersma MG, Bogaards JJ, Fiamegos YC, Schilter B, van Bladeren PJ, Cnubben NH, Rietjens IM. 2007. Human cytochrome P450 enzyme specificity for the bioactivation of estragole and related alkenylbenzenes. Chem Res Toxicol. 20(5):798–806.
  • Jeurissen SM, Punt A, Delatour T, Rietjens IM. 2008. Basil extract inhibits the sulfotransferase mediated formation of DNA adducts of the procarcinogen 1'-hydroxyestragole by rat and human liver S9 homogenates and in HepG2 human hepatoma cells. Food Chem Toxicol. 46(6):2296–2302.
  • Ji K, Chen J, Li M, Liu Z, Xia L, Wang C, Zhan Z, Wu X. 2009. Comments on serious anaphylaxis caused by nine Chinese herbal injections used to treat common colds and upper respiratory tract infections. Regul Toxicol Pharmacol. 55(2):134–138.
  • Ji L, Lu D, Cao J, Zheng L, Peng Y, Zheng J. 2015. Psoralen, a mechanism-based inactivator of CYP2B6. Chem Biol Interact. 240:346–532.
  • Jia S, Hu C. 2010. Pharmacological effects of rutaecarpine as a cardiovascular protective agent. Molecules. 15(3):1873–1881.
  • Jiang J, Hu C. 2009. Evodiamine: a novel anti-cancer alkaloid from Evodia rutaecarpa. Molecules. 14(5):1852–1859.
  • Jiang LL, Jiang Y, Zhao DS, Fan YX, Yu Q, Li P, Li HJ. 2018. CYP3A activation and glutathione depletion aggravate emodin-induced liver injury. Chem Res Toxicol. 31(10):1052–1060.
  • Jiang LL, Zhao DS, Fan YX, Yu Q, Li P, Li HJ. 2017. Detection of emodin derived glutathione adduct in normal rats administered with large dosage of Polygoni Multiflori Radix. Front Pharmacol. 8:446.
  • Jiao D, Smith TJ, Kim S, Yang CS, Desai D, Amin S, Chung FL. 1996. The essential role of the functional group in alkyl isothiocyanates for inhibition of tobacco nitrosamine-induced lung tumorigenesis. Carcinogenesis. 17(4):755–759.
  • Jin H, Dai J, Chen X, Liu J, Zhong D, Gu Y, Zheng J. 2010. Pulmonary toxicity and metabolic activation of dauricine in CD-1 mice. J Pharmacol Exp Ther. 332(3):738–746.
  • Jin H, Li L, Zhong D, Liu J, Chen X, Zheng J. 2011. Pulmonary toxicity and metabolic activation of tetrandrine in CD-1 mice. Chem Res Toxicol. 24(12):2142–2152.
  • Jin H, Shen S, Chen X, Zhong D, Zheng J. 2012. CYP3A-mediated apoptosis of dauricine in cultured human bronchial epithelial cells and in lungs of CD-1 mice. Toxicol Appl Pharmacol. 261(3):248–254.
  • Jin L, Baillie TA. 1997. Metabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in rats. Chem Res Toxicol. 10(3):318–327.
  • Jodynis-Liebert J, Murias M, Błoszyk E. 2000. Effect of sesquiterpene lactones on antioxidant enzymes and some drug-metabolizing enzymes in rat liver and kidney. Planta Med. 66(3):199–205.
  • Johnson BM, Qiu SX, Zhang S, Zhang F, Burdette JE, Yu L, Bolton JL, van Breemen RB. 2003. Identification of novel electrophilic metabolites of piper methysticum Forst (Kava). Chem Res Toxicol. 16(6):733–740.
  • Jung KA, Min HJ, Yoo SS, Kim HJ, Choi SN, Ha CY, Kim HJ, Kim TH, Jung WT, Lee OJ, et al. 2011. Drug-induced liver injury: twenty five cases of acute hepatitis following ingestion of polygonum multiflorum thunb. Gut Liver. 5(4):493–499.
  • Kalgutkar AS, Dalvie DK, O'Donnell JP, Taylor TJ, Sahakian DC. 2002. On the diversity of oxidative bioactivation reactions on nitrogen-containing xenobiotics. CDM. 3(4):379–424.
  • Kang KA, Piao MJ, Hyun YJ, Zhen AX, Cho SJ, Ahn MJ, Yi JM, Hyun JW. 2019. Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells. Exp Mol Med. 51(4):40.
  • Kassahun K, Skordos K, McIntosh I, Slaughter D, Doss GA, Baillie TA, Yost GS. 2005. Zafirlukast metabolism by cytochrome P450 3A4 produces an electrophilic alpha,beta-unsaturated iminium species that results in the selective mechanism-based inactivation of the enzyme. Chem Res Toxicol. 18(9):1427–1437.
  • Kent UM, Aviram M, Rosenblat M, Hollenberg PF. 2002. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos. 30(6):709–715.
  • Kent UM, Roberts-Kirchhoff ES, Moon N, Dunham WR, Hollenberg PF. 2001. Spectral studies of tert-butyl isothiocyanate-inactivated P450 2E1. Biochemistry. 40(24):7253–7261.
  • Khojasteh SC, Hartley DP, Ford KA, Uppal H, Oishi S, Nelson SD. 2012. Characterization of rat liver proteins adducted by reactive metabolites of menthofuran. Chem Res Toxicol. 25(11):2301–2309.
  • Kim HJ, Lee KW, Kim MS, Lee HJ. 2008. Piceatannol attenuates hydrogen-peroxide- and peroxynitrite-induced apoptosis of PC12 cells by blocking down-regulation of Bcl-XL and activation of JNK. J Nutr Biochem. 19(7):459–466.
  • Kim HY, Stermitz FR, Molyneux RJ, Wilson DW, Taylor D, Coulombe RA, Jr. 1993. Structural influences on pyrrolizidine alkaloid-induced cytopathology. Toxicol Appl Pharmacol. 122(1):61–69.
  • Kim S, Kim DH, Lee SH, Kim MJ, Yoon JH, Chung HY, Na CS, Kim ND. 2013. Urushiol induces apoptosis via a p53-dependent pathway in human gastric cancer cells. J Cancer Prev. 18(2):169–176.
  • Kim S, Lee HG, Park SA, Kundu JK, Keum YS, Cha YN, Na HK, Surh YJ. 2014. Keap1 cysteine 288 as a potential target for diallyl trisulfide-induced Nrf2 activation. PLoS One. 9(1):e85984.
  • Klein CB, King AA. 2007. Genistein genotoxicity: critical considerations of in vitro exposure dose. Toxicol Appl Pharmacol. 224(1):1–11.
  • Ko JW, Shin JY, Kim JW, Park SH, Shin NR, Lee IC, Shin IS, Moon C, Kim SH, Kim SH, Kim JC. 2017. Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: a possible role of CYP2E1 and NF-κB. Food Chem Toxicol. 102:156–165..
  • Koenigs LL, Trager WF. 1998. Mechanism-based inactivation of cytochrome P450 2B1 by 8-methoxypsoralen and several other furanocoumarins. Biochemistry. 37(38):13184–13193.
  • Kolm RH, Danielson UH, Zhang Y, Talalay P, Mannervik B. 1995. Isothiocyanates as substrates for human glutathione transferases: structure-activity studies. Biochem J. 311(2):453–459.
  • Komatsu K, Wakame K, Kano Y. 1993. Pharmacological properties of galenical preparation. XVI. Pharmacokinetics of evodiamine and the metabolite in rats. Biol Pharm Bull. 16(9):935–938.
  • Kouzi SA, McMurtry RJ, Nelson SD. 1994. Hepatotoxicity of germander (Teucrium chamaedrys L.) and one of its constituent neoclerodane diterpenes teucrin A in the mouse. Chem Res Toxicol. 7(6):850–856.
  • Křen V, Marhol P, Purchartová K, Gabrielová E, Modrianský M. 2013. Biotransformation of silybin and its congeners. Curr Drug Metab. 14(10):1009–1021.
  • Lake BG, Gray TJ, Evans JG, Lewis DF, Beamand JA, Hue KL. 1989. Studies on the mechanism of coumarin-induced toxicity in rat hepatocytes: comparison with dihydrocoumarin and other coumarin metabolites. Toxicol Appl Pharmacol. 97(2):311–323.
  • Lake BG. 1999. Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment. Food Chem Toxicol. 37(4):423–453.
  • Lam TK, Gallicchio L, Lindsley K, Shiels M, Hammond E, Tao XG, Chen L, Robinson KA, Caulfield LE, Herman JG, et al. 2009. Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev. 18(1):184–195.
  • Lambert JD, Zhao D, Meyers RO, Kuester RK, Timmermann BN, Dorr RT. 2002. Nordihydroguaiaretic acid: hepatotoxicity and detoxification in the mouse. Toxicon. 40(12):1701–1708.
  • Länger R, Stöger E, Kubelka W, Helliwell K. 2018. Quality standards for herbal drugs and herbal drug preparations - appropriate or improvements necessary? Planta Med. 84(6–07):350–360.
  • Larrey D, Faure S. 2011. Herbal medicine hepatotoxicity: a new step with development of specific biomarkers. J Hepatol. 54(4):599–601.
  • Larrey D, Vial T, Pauwels A, Castot A, Biour M, David M, Michel H. 1992. Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity. Ann Intern Med. 117(2):129–132.
  • Lawrence NJ, McGown AT, Nduka J, Hadfield JA, Pritchard RG. 2001. Cytotoxic Michael-type amine adducts of alpha-methylene lactones alantolactone and isoalantolactone. Bioorg Med Chem Lett. 1:429–431.
  • Lecoeur S, André C, Beaune PH. 1996. Tienilic acid-induced autoimmune hepatitis: anti-liver and-kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9. Mol Pharmacol. 50(2):326–333.
  • Lee HH, Park SA, Almazari I, Kim EH, Na HK, Surh YJ. 2010. Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling. Arch Biochem Biophys. 501(1):142–150.
  • Lee IC, Kim SH, Baek HS, Moon C, Kang SS, Kim SH, Kim YB, Shin IS, Kim JC. 2014. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats. Food Chem Toxicol. 63:174–185.
  • Lee MH, Kao L, Lin C. 2011. Comparison of the antioxidant and transmembrane permeative activities of the different Polygonum cuspidatum extracts in phospholipid-based microemulsions. J Agric Food Chem. 59(17):9135–9141.
  • Lee MS. 1996. Enzyme induction and comparative oxidative desulfuration of isothiocyanates to isocyanates. Chem Res Toxicol. 9(7):1072–1078.
  • Lei X, Chen J, Ren J, Li Y, Zhai J, Mu W, Zhang L, Zheng W, Tian G, Shang H, et al. 2015. Liver damage associated with Polygonum multiflorum thunb.: a systematic review of case reports and case series. Evid Based Complement Alternat Med. 2015:1.
  • Lekehal M, Pessayre D, Lereau JM, Moulis C, Fouraste I, Fau D. 1996. Hepatotoxicity of the herbal medicine germander: metabolic activation of its furano diterpenoids by cytochrome P450 3A depletes cytoskeleton-associated protein thiols and forms plasma membrane blebs in rat hepatocytes. Hepatology. 24(1):212–218.
  • Li A, Gao M, Zhao N, Li P, Zhu J, Li W. 2019. Acute liver failure associated with Fructus Psoraleae: a case report and literature review. BMC Complement Altern Med. 19(1):84.
  • Li H, Wang X, Liu Y, Pan D, Wang Y, Yang N, Xiang L, Cai X, Feng Y. 2017. Hepatoprotection and hepatotoxicity of heshouwu, a Chinese medicinal herb: context of the paradoxical effect. Food Chem Toxicol. 108(Pt B):407–418.
  • Li N, Xia Q, Ruan J, Fu PP, Lin G. 2011. Hepatotoxicity and tumorigenicity induced by metabolic activation of pyrrolizidine alkaloids in herbs. Curr Drug Metab. 12(9):823–834.
  • Li W, Lin D, Gao H, Xu Y, Meng D, Smith CV, Peng Y, Zheng J. 2016. Metabolic activation of furan moiety makes Diosbulbin B hepatotoxic. Arch Toxicol. 90(4):863–872.
  • Li Z, Feng H, Wang Y, Shen B, Tian Y, Wu L, Zhang Q, Jin M, Liu G. 2019. Rosmarinic acid protects mice from lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting MAPKs/NF-κB and activating Nrf2/HO-1 signaling pathways. Int Immunopharmacol. 67:465–472.
  • Li ZJ, Abulizi A, Zhao GL, Wang T, Zhou F, Jiang ZZ, Aibai S, Zhang LY. 2017. Bakuchiol contributes to the hepatotoxicity of psoralea corylifolia in rats. Phytother Res. 31(8):1265–1272.
  • Lin D, Guo X, Gao H, Cheng L, Cheng M, Song S, Peng Y, Zheng J. 2015. In vitro and in vivo studies of the metabolic activation of 8-epidiosbulbin E acetate. Chem Res Toxicol. 28(9):1737–1746.
  • Lin D, Li C, Peng Y, Gao H, Zheng J. 2014. Cytochrome p450-mediated metabolic activation of diosbulbin B. Drug Metab Dispos. 42(10):1727–1736.
  • Lin D, Li W, Peng Y, Jiang C, Xu Y, Gao H, Zheng J. 2016. Role of metabolic activation in 8-epidiosbulbin E acetate-induced liver injury: mechanism of action of the hepatotoxic furanoid. Chem Res Toxicol. 29(3):359–366.
  • Lin D, Li W, Tian X, Peng Y, Zheng J. 2019. In vitro DNA adduction resulting from metabolic activation of diosbulbin B and 8-epidiosbulbin E acetate. Chem Res Toxicol. 32(1):38–48.
  • Lin D, Wang K, Guo X, Gao H, Peng Y, Zheng J. 2016. Lysine- and cysteine-based protein adductions derived from toxic metabolites of 8-epidiosbulbin E acetate. Toxicol Lett. 264:20–28.
  • Lin G, Cui YY, Liu XQ. 2003. Gender differences in microsomal metabolic activation of hepatotoxic clivorine in rat. Chem Res Toxicol. 16(6):768–774.
  • Lin HL, Kenaan C, Hollenberg PF. 2012. Identification of the residue in human CYP3A4 that is covalently modified by bergamottin and the reactive intermediate that contributes to the grapefruit juice effect. Drug Metab Dispos. 40(5):998–1006.
  • Lin HL, Kent UM, Hollenberg PF. 2005. The grapefruit juice effect is not limited to cytochrome P450 (P450) 3A4: evidence for bergamottin-dependent inactivation, heme destruction, and covalent binding to protein in P450s 2B6 and 3A5. J Pharmacol Exp Ther. 313(1):154–164.
  • Lin L, Ni B, Lin H, Zhang M, Li X, Yin X, Qu C, Ni J. 2015. Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum thunb: a review. J Ethnopharmacol. 159:158–183.
  • Liu B, Yuan B, Zhang L, Mu W, Wang C. 2015. ROS/p38/p53/Puma signaling pathway is involved in emodin-induced apoptosis of human colorectal cancer cells. Int J Clin Exp Med. 8(9):15413–15422.
  • Liu R, Zhou F, He H, Wei J, Tian X, Ding L. 2018. Metabolism and bioactivation of corynoline with characterization of the glutathione/cysteine conjugate and evaluation of its hepatotoxicity in mice. Front Pharmacol. 9:1264.
  • Liu Y, Cui T, Peng Y, Ji M, Zheng J. 2019. Mechanism-based inactivation of cytochrome P450 2D6 by chelidonine. J Biochem Mol Toxicol. 33(2):e22251.
  • Loeper J, Descatoire V, Letteron P, Moulis C, Degott C, Dansette P, Fau D, Pessayre D. 1994. Hepatotoxicity of germander in mice. Gastroenterology. 106(2):464–472.
  • Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB. 1997. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest. 99(10):2545–2553.
  • Lu D, Ji L, Zheng L, Cao J, Peng Y, Zheng J. 2016. Mechanism-based inactivation of cytochrome P450 2B6 by isopsoralen. Xenobiotica. 46(4):335–341.
  • Lü JM, Nurko J, Weakley SM, Jiang J, Kougias P, Lin PH, Yao Q, Chen C. 2010. Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: an update. Med Sci Monit. 16(5):RA93–100.
  • Lundahl J, Regårdh CG, Edgar B, Johnsson G. 1997. Effects of grapefruit juice ingestion – pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur J Clin Pharmacol. 52(2):139–145.
  • Luo G, Guenthner TM. 1996. Covalent binding to DNA in vitro of 2',3'-oxides derived from allylbenzene analogs. Drug Metab Dispos. 24(9):1020–1027.
  • Lv GP, Meng LZ, Han DQ, Li HY, Zhao J, Li SP. 2015. Effect of sample preparation on components and liver toxicity of Polygonum multiflorum. J Pharm Biomed Anal. 109:105–111.
  • Ma J, Zheng L, He YS, Li HJ. 2015. Hepatotoxic assessment of Polygoni Multiflori Radix extract and toxicokinetic study of stilbene glucoside and anthraquinones in rats. J Ethnopharmacol. 162:61–68.
  • Mao X, Hu Z, Wang Q, Zhang N, Zhou S, Peng Y, Zheng J. 2018. Nitidine chloride is a mechanism-based inactivator of CYP2D6. Drug Metab Dispos. 46(8):1137–1145.
  • Mao X, Peng Y, Zheng J. 2015. In vitro and in vivo characterization of reactive intermediates of corynoline. Drug Metab Dispos. 43(10):1491–1498.
  • Marles RJ, Pazos-Sanou L, Compadre CM, Pezutto JM, Błoszyk E, Arnason T. 1995. Sesquiterpene lactones revisited. In: Arnason JT, Mata R, Romeo JT, editors Recent advances in phytochemistry, vol. 29. New York and London: Phytochemistry of Medicinal Plants Plenum Press; Chapter 13, p. 334–340.
  • Mathews JM, Etheridge AS, Black SR. 2002. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos. 30(11):1153–1157.
  • Mathews JM, Etheridge AS, Valentine JL, Black SR, Coleman DP, Patel P, So J, Burka LT. 2005. Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro. Drug Metab Dispos. 33(10):1555–1563.
  • Mazzanti G, Battinelli L, Daniele C, Mastroianni CM, Lichtner M, Coletta S, Costantini S. 2004. New case of acute hepatitis following the consumption of Shou Wu Pian, a Chinese herbal product derived from Polygonum multiflorum. Ann Intern Med. 140(7):W-30.
  • Mi L, Xiao Z, Hood BL, Dakshanamurthy S, Wang X, Govind S, Conrads TP, Veenstra TD, Chung FL. 2008. Covalent binding to tubulin by isothiocyanates. A mechanism of cell growth arrest and apoptosis. J Biol Chem. 283(32):22136–22146.
  • Mi L, Di Pasqua AJ, Chung FL. 2011. Proteins as binding targets of isothiocyanates in cancer prevention. Carcinogenesis. 32(10):1405–1413.
  • Miller EC, Swanson AB, Phillips DH, Fletcher TL, Liem A, Miller JA. 1983. Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole. Cancer Res. 43(3):1124–1134.
  • Monks TJ, Jones DC. 2002. The metabolism and toxicity of quinones, quinonimines, quinone methides, and quinone-thioethers. CDM. 3(4):425–438.
  • Moridani MY, Scobie H, Salehi P, O'Brien PJ. 2001. Catechin metabolism: glutathione conjugate formation catalyzed by tyrosinase, peroxidase, and cytochrome p450. Chem Res Toxicol. 14(7):841–848.
  • Morse MA, Amin SG, Hecht SS, Chung FL. 1989. Effects of aromatic isothiocyanates on tumorigenicity, O6-methylguanine formation, and metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung. Cancer Res. 49(11):2894–2897.
  • Morse MA, Lu J, Stoner GD, Murphy SE, Peterson LA. 1999. Metabolism of N-nitrosobenzylmethylamine by human cytochrome P-450 enzymes. J Toxicol Environ Health A. 58(7):397–411.
  • Mostefa-Kara N, Pauwels A, Pines E, Biour M, Levy VG. 1992. Fatal hepatitis after herbal tea. Lancet. 340(8820):674.
  • Murata M, Midorikawa K, Koh M, Umezawa K, Kawanishi S. 2004. Genistein and daidzein induce cell proliferation and their metabolites cause oxidative DNA damage in relation to isoflavone-induced cancer of estrogen-sensitive organs. Biochemistry. 43(9):2569–2577.
  • Murray M. 2000. Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds on cytochrome P450-dependent drug oxidation. Curr Drug Metab. 1(1):67–84.
  • Nahin RL, Barnes PM, Stussman BJ, Bloom B. 2009. Costs of complementary and alternative medicine (CAM) and frequency of visits to CAM practitioners: United States, 2007. Natl Health Stat Report. 18:1–14.
  • Nakajima M, Yoshida R, Shimada N, Yamazaki H, Yokoi T. 2001. Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate. Drug Metab Dispos. 29(8):1110–1113.
  • Nakamura T, Abe-Kanoh N, Nakamura Y. 2018. Physiological relevance of covalent protein modification by dietary isothiocyanates. J Clin Biochem Nutr. 62(1):11–19.
  • Nam SW, Baek JT, Lee DS, Kang SB, Ahn BM, Chung KW. 2005. A case of acute cholestatic hepatitis associated with the seeds of Psoralea corylifolia (Boh-Gol-Zhee). Clin Toxicol (Phila). 43(6):589–591.
  • National Toxiclogy Program. NTP technical report. 2001. The Toxicology and Carcinogenesis Studies of Emodin in F344/N Rats and B6C3F1 Mice (Report No. 01-3952) NIH Publication (2001) (PP1–278).
  • National Toxicology Program (NTP). 1983. Carcinogenesis studies of eugenol (CAS No. 97‐53‐0) in F344/N rats and B6C3F1 mice (feed studies). National Toxicology Program Toxicity Report Series Number 223, NIH publication No. 84-1779. pp. 1–159.
  • National Toxicology Program (NTP). 2000. NTP toxicology and carcinogenesis studies of methyleugenol (CAS NO. 93-15-2) in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program Toxicology Report Series Number 491, NIH publication No. 00-3950. pp. 1–412.
  • National Toxicology Program (NTP). 2010. Toxicology and carcinogenesis studies of isoeugenol (CAS No. 97‐54‐1) in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program Toxicity Report Series Number 551, NIH Publication No. 10-5892. pp. 1–178.
  • Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH. 2017. Liver injury from herbal and dietary supplements. Hepatology. 65(1):363–373.
  • Nelson SD, McClanahan RH, Thomassen D, Gordon WP, Knebel N. 1992. Investigations of mechanisms of reactive metabolite formation from (R)-(+)-pulegone. Xenobiotica. 22(9–10):1157–1164.
  • Ober D, Hartmann T. 1999. Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase. Proc Natl Acad Sci USA. 96(26):14777–14782.
  • Oikawa S, Nagao E, Sakano K, Kawanishi S. 2006. Mechanism of oxidative DNA damage induced by capsaicin, a principal ingredient of hot chili pepper. Free Radic Res. 40(9):966–973.
  • Ojala T, Remes S, Haansuu P, Vuorela H, Hiltunen R, Haahtela K, Vuorela P. 2000. Antimicrobial activity of some coumarin containing herbal plants growing in Finland. J Ethnopharmacol. 73(1-2):299–305.
  • Olsen LR1, Grillo MP, Skonberg C. 2011. Constituents in kava extracts potentially involved in hepatotoxicity: a review. Chem Res Toxicol. 24(7):992–1002.
  • Ou Q, Weng Y, Wang S, Zhao Y, Zhang F, Zhou J, Wu X. 2018. Silybin Alleviates Hepatic Steatosis and Fibrosis in NASH Mice by Inhibiting Oxidative Stress and Involvement with the Nf-κB Pathway. Dig Dis Sci. 63(12):3398–3408.
  • Paine MF, Criss AB, Watkins PB. 2004. Two major grapefruit juice components differ in intestinal CYP3A4 inhibition kinetic and binding properties. Drug Metab Dispos. 32(10):1146–1153.
  • Panis B, Wong DR, Hooymans PM, De Smet PA, Rosias PP. 2005. Recurrent toxic hepatitis in a Caucasian girl related to the use of Shou-Wu-Pian, a Chinese herbal preparation. J Pediatr Gastroenterol Nutr. 41(2):256–258.
  • Park BK, Boobis A, Clarke S, Goldring CE, Jones D, Kenna JG, Lambert C, Laverty HG, Naisbitt DJ, Nelson S, et al. 2011. Managing the challenge of chemically reactive metabolites in drug development. Nat Rev Drug Discov. 10(4):292–306.
  • Park GJ, Mann SP, Ngu MC. 2001. Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum. J Gastroenterol Hepatol. 16(1):115–117.
  • Peng W, Qin R, Li X, Zhou H. 2013. Botany, phytochemistry, pharmacology, and potential application of Polygonum cuspidatum Sieb.et Zucc.: a review. J Ethnopharmacol. 148(3):729–745.
  • Petersen M, Simmonds MS. 2003. Rosmarinic acid. Phytochemistry. 62(2):121–125.
  • Phillips DH, Reddy MV, Randerath K. 1984. 32P-post-labelling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally-occurring alkenylbenzenes. II. Newborn male B6C3F1 mice . Carcinogenesis. 5(12):1623–1628.
  • Piver B, Fer M, Vitrac X, Merillon JM, Dreano Y, Berthou F, Lucas D. 2004. Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes. Biochem Pharmacol. 68(4):773–782.
  • Porter R, Parry EM, Parry JM. 1992. Morphological transformation of an established Syrian hamster dermal cell with the anti-tussive agent noscapine. Mutagenesis. 7(3):205–209.
  • Potter GA, Patterson LH, Wanogho E, Perry PJ, Butler PC, Ijaz T, Ruparelia KC, Lamb JH, Farmer PB, Stanley LA, Burke MD. 2002. The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1. Br J Cancer. 86(5):774–778.
  • Premdas PD, Bowers RJ, Forkert PG. 2000. Inactivation of hepatic CYP2E1 by an epoxide of diallyl sulfone. J Pharmacol Exp Ther. 293(3):1112–1120.
  • Priestap HA, Torres MC, Rieger RA, Dickman KG, Freshwater T, Taft DR, Barbieri MA, Iden CR. 2012. Aristolochic acid I metabolism in the isolated perfused rat kidney. Chem Res Toxicol. 25(1):130–139.
  • Purchase R, Ford GP, Creasy DM, Brantom PG, Gangolli SD. 1992. A 28-day feeding study with methyl isoeugenol in rats. Food Chem Toxicol. 30(6):475–481.
  • Qin B, Xu Y, Chen J, Huang W, Peng Y, Zheng J. 2016. Chemical Reactivity of Emodin and Its Oxidative Metabolites to Thiols. Chem Res Toxicol. 29(12):2114–2124.
  • Qin CZ, Lv QL, Wu NY, Cheng L, Chu YC, Chu TY, Hu L, Cheng Y, Zhang X, Zhou HH. 2015. Mechanism-based inhibition of Alantolactone on human cytochrome P450 3A4 in vitro and activity of hepatic cytochrome P450 in mice. J Ethnopharmacol. 168:146–149.
  • Qin X, Peng Y, Zheng J. 2018. In Vitro and in Vivo Studies of the Electrophilicity of Physcion and its Oxidative Metabolites. Chem Res Toxicol. 31(5):340–349.
  • Qu K, Shen NY, Xu XS, Su HB, Wei JC, Tai MH, Meng FD, Zhou L, Zhang YL, Liu C. 2013. Emodin induces human T cell apoptosis in vitro by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction. Acta Pharmacol Sin. 34(9):1217–1228.
  • Rajakumar T, Pugalendhi P, Thilagavathi S, Ananthakrishnan D, Gunasekaran K. 2018. Allyl isothiocyanate, a potent chemopreventive agent targets AhR/Nrf2 signaling pathway in chemically induced mammary carcinogenesis. Mol Cell Biochem. 437(1–2):1–12.
  • Randerath K, Haglund RE, Phillips DH, Reddy MV. 1984. 32P-postlabeling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally-occurring alkenylbenzenes. I. Adult female CD-1 mice. Carcinogenesis. 5(12):1613–1622.
  • Rao PS, Midde NM, Miller DD, Chauhan S, Kumar A, Kumar S. 2015. Diallyl sulfide: potential use in novel therapeutic interventions in alcohol, drugs, and disease mediated cellular toxicity by targeting cytochrome P450 2E1. Curr Drug Metab. 16(6):486–503.
  • Rasul A, Khan M, Ali M, Li J, Li X. 2013. Targeting apoptosis pathways in cancer with alantolactone and isoalantolactone. ScientificWorldJournal. 2013:1.
  • Reilly CA, Crouc DJ, Yost GS, Fatah AA. 2001. Determination of capsaicin, dihydrocapsaicin, and nonivamide in self-defense weapons by liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. J Chromatogr A. 912(2):259–267.
  • Reilly CA, Henion F, Bugni TS, Ethirajan M, Stockmann C, Pramanik KC, Srivastava SK, Yost GS. 2013. Reactive intermediates produced from the metabolism of the vanilloid ring of capsaicinoids by p450 enzymes. Chem Res Toxicol. 26(1):55–66.
  • Rietjens IM, Al Huseiny W, Boersma MG. 2011. Flavonoids and alkenylbenzenes: new concepts in bioactivation studies. Chem Biol Interact. 192(1–2):87–95.
  • Rietjens IM, Boersma MG, van der Woude H, Jeurissen SM, Schutte ME, Alink GM. 2005. Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk. Mutat Res. 574(1–2):124–138.
  • Rietjens IM, Cohen SM, Fukushima S, Gooderham NJ, Hecht S, Marnett LJ, Smith RL, Adams TB, Bastaki M, Harman CG, Taylor SV. 2014. Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. Chem Res Toxicol. 27(7):1092–1103.
  • Roeder E, Wiedenfeld H, Edgar JA. 2015. Pyrrolizidine alkaloids in medicinal plants from North America. Pharmazie. 70(6):357–367.
  • Roeder E. 1995. Medicinal plants in Europe containing pyrrolizidine alkaloids. Pharmazie. 50(2):83–98.
  • Rosenblat M, Belinky P, Vaya J, Levy R, Hayek T, Coleman R, Merchav S, Aviram M. 1999. Macrophage enrichment with the isoflavan glabridin inhibits NADPH oxidase-induced cell-mediated oxidation of low density lipoprotein. A possible role for protein kinase C. J Biol Chem. 274(20):13790–13799.
  • Rosenborg S, Stenberg M, Otto S, Ostervall J, Masquelier M, Yue QY, Bertilsson L, Eliasson E. 2010. Clinically significant CYP2C inhibition by noscapine but not by glucosamine. Clin Pharmacol Ther. 88(3):343–346.
  • Rosenquist TA, Einolf HJ, Dickman KG, Wang L, Smith A, Grollman AP. 2010. Cytochrome P450 1A2 detoxicates aristolochic acid in the mouse. Drug Metab Dispos. 38(5):761–768.
  • Ruan J, Yang M, Fu P, Ye Y, Lin G. 2014. Metabolic activation of pyrrolizidine alkaloids: insights into the structural and enzymatic basis. Chem Res Toxicol. 27(6):1030–1039.
  • Sangster SA, Caldwell J, Hutt AJ, Anthony A, Smith RL. 1987. The metabolic disposition of [methoxy-14C]-labelled trans-anethole, estragole and p-propylanisole in human volunteers. Xenobiotica. 17(10):1223–1232.
  • Satoh T, Kosaka K, Itoh K, Kobayashi A, Yamamoto M, Shimojo Y, Kitajima C, Cui J, Kamins J, Okamoto S-I, et al. 2008. Lipton SA Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1. J Neurochem. 104(4):1116–1131.,
  • Schmeiser HH, Nortier JL, Singh R, Gamboa da Costa G, Sennesael J, Cassuto-Viguier E, Ambrosetti D, Rorive S, Pozdzik A, Phillips DH, et al. 2014. Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid d nephropathy. Int J Cancer. 135(2):502–507.
  • Schmeiser HH1, Kucab JE, Arlt VM, Phillips DH, Hollstein M, Gluhovschi G, Gluhovschi C, Modilca M, Daminescu L, Petrica L, Velciov S. 2012. Evidence of exposure to aristolochic acid in patients with urothelial cancer from a Balkan endemic nephropathy region of Romania. Environ Mol Mutagen. 53(8):636–641.
  • Schmidt TJ, Nour AM, Khalid SA, Kaiser M, Brun R. 2009. Quantitative structure–antiprotozoal activity relationships of sesquiterpene lactones. Molecules. 14(6):2062–2076.
  • Schmidt TJ. 1997. Helenanolide-type sesquiterpene lactones–III. Rates and stereochemistry in the reaction of helenalin and related helenanolides with sulfhydryl containing biomolecules. Bioorg Med Chem. 5(4):645–653.
  • Schmiedlin-Ren P, Edwards DJ, Fitzsimmons ME, He K, Lown KS, Woster PM, Rahman A, Thummel KE, Fisher JM, Hollenberg PF, Watkins PB. 1997. Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab Dispos. 25(11):1228–1233.
  • Schramm S, Köhler N, Rozhon W. 2019. Pyrrolizidine alkaloids: biosynthesis, biological activities and occurrence in crop plants. Molecules. 24(3):498.
  • Scordo MG, Melhus H, Stjernberg E, Edvardsson AM, Wadelius M. 2008. Warfarin-noscapine interaction: a series of four case reports. Ann Pharmacother. 42(3):448–450.
  • Seden K, Dickinson L, Khoo S, Back D. 2010. Grapefruit-drug interactions. Drugs. 70(18):2373–2407.
  • Seelinger G, Merfort I, Schempp CM. 2008. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med. 74(14):1667–1677.
  • Seo JY, Lim SS, Kim JR, Lim JS, Ha YR, Lee IA, Kim EJ, Park JH, Kim JS. 2008. Nrf2-mediated induction of detoxifying enzymes by alantolactone present in Inula helenium. Phytother Res. 22(11):1500–1505.
  • Seo JY, Park J, Kim HJ, Lee IA, Lim JS, Lim SS, Choi SJ, Park JH, Kang HJ, Kim JS. 2009. Isoalantolactone from Inula helenium caused Nrf2-mediated induction of detoxifying enzymes. J Med Food. 12(5):1038–1045.
  • Sharma A, Kashyap D, Sak K, Tuli HS, Sharma AK. 2018. Therapeutic charm of quercetin and its derivatives: a review of research and patents. Pharm Pat Anal. 7(1):15–32.
  • Sharma SK, Vij AS, Sharma M. 2013. Mechanisms and clinical uses of capsaicin. Eur J Pharmacol. 720(1–3):55–62.
  • Sheikh NM, Philen RM, Love LA. 1997. Chaparral-associated hepatotoxicity. Arch Intern Med. 157(8):913–919.
  • Sheu JR, Hung WC, Wu CH, Lee YM, Yen MH. 2000. Antithrombotic effect of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, on platelet plug formation in in vivo experiments. Br J Haematol. 110(1):110–115.
  • Shi P, Lin X, Yao H. 2018. A comprehensive review of recent studies on pharmacokinetics of traditional Chinese medicines (2014-2017) and perspectives. Drug Metab Rev. 50(2):161–192.
  • Shi F, Zhao P, Li X, Pan H, Ma S, Ding L. 2015. Cytotoxicity of luteolin in primary rat hepatocytes: the role of CYP3A-mediated ortho-benzoquinone metabolite formation and glutathione depletion. J Appl Toxicol. 35(11):1372–1380.
  • Sidorenko VS, Attaluri S, Zaitseva I, Iden CR, Dickman KG, Johnson F, Grollman AP. 2014. Bioactivation of the human carcinogen aristolochic acid. Carcinogenesis. 35(8):1814–1822.
  • Simmler C, Pauli GF, Chen SN. 2013. Phytochemistry and biological properties of glabridin. Fitoterapia. 90:160–184.
  • Singh BN, Shankar S, Srivastava RK. 2011. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol. 82(12):1807–1821.
  • Smith LW, Culvenor CC. 1981. Plant sources of hepatotoxic pyrrolizidine alkaloids. J Nat Prod. 44(2):129–152.
  • Smith RL, Adams TB, Doull J, Feron VJ, Goodman JI, Marnett LJ, Portoghese PS, Waddell WJ, Wagner BM, Rogers AE, et al. 2002. Safety assessment of allylalkoxybenzene derivatives used as flavouring substances - methyl eugenol and estragole. Food Chem Toxicol. 40(7):851–870.
  • Smith TJ, Guo Z, Li C, Ning SM, Thomas PE, Yang CS. 1993. Mechanisms of inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bioactivation in mouse by dietary phenethyl isothiocyanate. Cancer Res. 53(14):3276–3282.
  • Solheim E, Scheline RR. 1976. Metabolism of alkenebenzene derivatives in the rat. II. Eugenol and isoeugenol methyl ethers. Xenobiotica. 6(3):137–150.
  • Son PS, Park SA, Na HK, Jue DM, Kim S, Surh YJ. 2010. Piceatannol, a catechol-type polyphenol, inhibits phorbol ester-induced NF-{kappa}B activation and cyclooxygenase-2 expression in human breast epithelial cells: cysteine 179 of IKK{beta} as a potential target. Carcinogenesis. 31(8):1442–1449.
  • Sridar C, Goosen TC, Kent UM, Williams JA, Hollenberg PF. 2004. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos. 32(6):587–594.
  • Srirama R, Santhosh Kumar JU, Seethapathy GS, Newmaster SG, Ragupathy S, Ganeshaiah KN, Uma Shaanker R, Ravikanth G. 2017. Species adulteration in the herbal trade: causes, consequences and mitigation. Drug Saf. 40(8):651–661.
  • Staretz ME, Foiles PG, Miglietta LM, Hecht SS. 1997. Evidence for an important role of DNA pyridyloxobutylation in rat lung carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: effects of dose and phenethyl isothiocyanate. Cancer Res. 57(2):259–266.
  • Stiborová M, Arlt VM, Schmeiser HH. 2017. DNA adducts formed by aristolochic acid are unique biomarkers of exposure and explain the initiation phase of upper urothelial cancer. IJMS. 18(10):2144.
  • Stiborová M, Arlt VM, Schmeiser HH. 2016. Balkan endemic nephropathy: an update on its aetiology. Arch Toxicol. 90(11):2595–2615.
  • Stiborová M, Frei E, Arlt VM, Schmeiser HH. 2014. Knockout and humanized mice as suitable tools to identify enzymes metabolizing the human carcinogen aristolochic acid. Xenobiotica. 44(2):135–145.
  • Stiborová M, Frei E, Hodek P, Wiessler M, Schmeiser HH. 2005. Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid-DNA adducts found in patients with urothelial cancer. Int J Cancer. 113(2):189–197.
  • Stournaras E, Tziomalos K. 2015. Herbal medicine-related hepatotoxicity. World J Hepatol. 7(19):2189–2193.
  • Sullivan JB, Rumack BH, Thomas H, Peterson RG, Bryson P. 1979. Pennyroyal oil poisoning and hepatotoxicity. Jama. 242(26):2873–2874.
  • Sun H, Yost GS. 2008. Metabolic activation of a novel 3-substituted indole-containing TNF-alpha inhibitor: dehydrogenation and inactivation of CYP3A4. Chem Res Toxicol. 21(2):374–385.
  • Sun Y, Xin X, Zhang K, Cui T, Peng Y, Zheng J. 2018. Cytochrome P450 mediated metabolic activation of chrysophanol. Chem Biol Interact. 289:57–67.
  • Sun Y, Yao T, Li H, Peng Y, Zheng J. 2017. In vitro and in vivo metabolic activation of berbamine to quinone methide intermediate. J Biochem Mol Toxicol. 31(4):e21876.
  • Surai PF. 2015. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants (Basel)). 4(1):204–247.
  • Surh YJ. 1998. Bioactivation of benzylic and allylic alcohols via sulfo-conjugation. Chem Biol Interact. 109(1-3):221–235.
  • Suzuki Y, Miyoshi N, Isemura M. 2012. Health-promoting effects of green tea. Proc Jpn Acad, Ser B, Phys Biol Sci. 88(3):88–101.
  • Tafazoli S, Spehar DD, O'Brien PJ. 2005. Oxidative stress mediated idiosyncratic drug toxicity. Drug Metabolism Revs. 37(2):311–325.
  • Tang CB, Zhang WG, Dai C, Li HX, Xu XL, Zhou GH. 2015. Identification and quantification of adducts between oxidized rosmarinic acid and thiol compounds by UHPLC-LTQ-Orbitrap and MALDI-TOF/TOF tandem mass spectrometry. J Agric Food Chem. 63(3):902–911.
  • Tang CB, Zhang WG, Wang YS, Xing LJ, Xu XL, Zhou GH. 2016. Identification of rosmarinic acid-adducted sites in meat proteins in a gel model under oxidative stress by triple TOF MS/MS. J Agric Food Chem. 64(33):6466–6476.
  • Tang W, Eisenbrand G. 1992. Evodia rutaecarpa (Juss) Benth. In: Tang W, Eisenbrand G, editors, Chinese drugs of plant origins. Berlin: Springer-Verlag, p. 509–514.
  • Tanigawa S, Fujii M, Hou DX. 2007. Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med. 42(11):1690–1703.
  • Teschke R, Zhang L, Long H, Schwarzenboeck A, Schmidt-Taenzer W, Genthner A, Wolff A, Frenzel C, Schulze J, Eickhoff A. 2015. Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases. Ann Hepatol. 14(1):7–19.
  • Teschke R. 2014. Traditional Chinese medicine induced liver injury. J Clin Transl Hepatol. 2(2):80–94.
  • Teyssier C, Guenot L, Suschetet M, Siess MH. 1999. Metabolism of diallyl disulfide by human liver microsomal cytochromes P-450 and flavin-containing monooxygenases. Drug Metab Dispos. 27(7):835–841.
  • Tian Y, Shen S, Jiang Y, Shen Q, Zeng S, Zheng J. 2016. CYP3A5 mediates bioactivation and cytotoxicity of tetrandrine. Arch Toxicol. 90(7):1737–1748.
  • Tomar V, Kukreti S, Prakash S, Madan J, Chandra R. 2017. Noscapine and its analogs as chemotherapeutic agent: current updates. Curr Top Med Chem. 17(2):174–188.
  • Tsai TH, Lee TF, Chen CF, Wang LC. 1995. Thermoregulatory effects of alkaloids isolated from Wu-chu-yu in afebrile and febrile rats. Pharmacol Biochem Behav. 50(2):293–298.
  • U.S. Food and Drug Administration. 2001. FDA Advises Dietary Supplement Manufacturers to Remove Comfrey Products from the Market; [accessed 2001 Jul 6]. http://www.fda.gov/Food/RecallsOutbreaksEmergencies/SafetyAlertsAdvisories/ucm111219.htm.
  • U.S. Food and Drug Administration (USFDA). 2010. Code of Federal Regulations. Title 21, Vol. 3, 21CFR172.515. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=172.515.
  • Umehara K, Kudo S, Hirao Y, Morita S, Ohtani T, Uchida M, Miyamoto G. 2000. In vitro characterization of the oxidative cleavage of the octyl side chain of olanexidine, a novel antimicrobial agent, in dog liver microsomes. Drug Metab Dispos. 28(12):1417–1424.
  • Usia T, Watabe T, Kadota S, Tezuka Y. 2005. Metabolite-cytochrome P450 complex formation by methylenedioxyphenyl lignans of Piper cubeba: mechanism-based inhibition. Life Sci. 76(20):2381–2391.
  • van der Woude H, Alink GM, van Rossum BE, Walle K, van Steeg H, Walle T, Rietjens IM. 2005. Formation of transient covalent protein and DNA adducts by quercetin in cells with and without oxidative enzyme activity. Chem Res Toxicol. 18(12):1907–1916.
  • Vanherweghem J-L, Tielemans C, Abramowicz D, Depierreux M, Vanhaelen-Fastre R, Vanhaelen M, Dratwa M, Richard C, Vandervelde D, Verbeelen D, et al. 1993. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet. 341(8842):387–391.
  • Vassallo JD, Hicks SM, Daston GP, Lehman-McKeeman LD. 2004. Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. Toxicol Sci. 80(2):249–257.
  • Viswanatharaju Ruddraraju K, Parsons ZD, Lewis CD, Gates KS. 2017. Allylation and alkylation of biologically relevant nucleophiles by diallyl sulfides. J Org Chem. 82(1):776–780.
  • Walle T, Hsieh F, DeLegge MH, Oatis JE, Jr, Walle UK. 2004. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 32(12):1377–1382.
  • Wang H, Wang K, Mao X, Zhang Q, Yao T, Peng Y, Zheng J. 2015. Mechanism-based inactivation of CYP2C9 by linderane. Xenobiotica. 45(12):1037–1046.
  • Wang J-B, Zhao H-P, Zhao Y-L, Jin C, Liu D-J, Kong W-J, Fang F, Zhang L, Wang H-J, Xiao X-h, et al. 2011. Hepatotoxicity or hepatoprotection? Pattern recognition for the paradoxical effect of the Chinese herb Rheum palmatum L. in treating rat liver injury. PLoS One. 6(9):e24498.
  • Wang K, Lin D, Guo X, Huang W, Peng Y, Zheng J. 2017. Chemical identity of interaction of protein with reactive metabolite of diosbulbin B in vitro and in vivo. Toxins (Basel). 9(8):249.
  • Wang L, He X, Jin C, Ondieki G. 2016. Mechanism-based inhibitors from phytomedicine: risks of hepatotoxicity and their potential hepatotoxic substructures. CDM. 17(10):971–991.
  • Wang M, Zhao R, Wang W, Mao X, Yu J. 2012. Lipid regulation effects of Polygoni Multiflori Radix, its processed products and its major substances on steatosis human liver cell line L02. J Ethnopharmacol. 139(1):287–293.
  • Wang PL, Zhang FX, Qiu ZC, Yao ZH, Wong MS, Yao XS, Dai Y. 2016. Isolation and identification of metabolites of bakuchiol in rats. Fitoterapia. 109:31–38.
  • Wang S, Fang K, Dong G, Chen S, Liu N, Miao Z, Yao J, Li J, Zhang W, Sheng C. 2015. Scaffold diversity inspired by the natural product evodiamine: discovery of highly potent and multitargeting antitumor agents. J Med Chem. 58(16):6678–6696.
  • Wang X, Xin X, Sun Y, Zou L, Li H, Zhao Y, Li R, Peng Y, Zheng J. 2019. Chemical reactivity of aloe-emodin and its hydroxylation metabolites to thiols. Chem Res Toxicol. 32(2):234–244.
  • Wang Y, Luo Q, He X, Wei H, Wang T, Shao J, Jiang X. 2018. Emodin induces apoptosis of colon cancer cells via induction of autophagy in a ROS-dependent manner. Oncol Res. 26(6):889–899.
  • Wang Y, Zhong D, Chen X, Zheng J. 2009. Identification of quinone methide metabolites of dauricine in human liver microsomes and in rat bile. Chem Res Toxicol. 22(5):824–834.
  • Wen B, Roongta V, Liu L, Moore DJ. 2014. Metabolic activation of the indoloquinazoline alkaloids evodiamine and rutaecarpine by human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4. Drug Metab Dispos. 42(6):1044–1054.
  • White IN, Mattocks AR, Butler WH. 1973. The conversion of the pyrrolizidine alkaloid retrorsine to pyrrolic derivatives in vivo and in vitro and its acute toxicity to various animal species. Chem Biol Interact. 6(4):207–218.
  • Widen JC, Kempema AM, Baur JW, Skopec HM, Edwards JT, Brown TJ, Brown DA, Meece FA, Harki DA. 2018. Helenalin analogues targeting NF-κB p65: thiol reactivity and cellular potency studies of varied electrophiles. ChemMedChem. 13(4):303–311.
  • Widen JC, Kempema AM, Villalta PW, Harki DA. 2017. Targeting NF-κB p65 with a Helenalin Inspired Bis-electrophile. ACS Chem Biol. 12(1):102–113.
  • Williams DE, Reed RL, Kedzierski B, Dannan GA, Guengerich FP, Buhler DR. 1989. Bioactivation and detoxication of the pyrrolizidine alkaloid senecionine by cytochrome P-450 enzymes in rat liver. Drug Metab Dispos. 17(4):387–392.
  • Williams GM, Mattia A. 2009. Alkoxy-substituted allylbenzenes present in foods and essential oils and sued as flavouring agents. In Data Safety Evaluation of Certain Food Additives/Prepared by the Sixty-Ninth Meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). WHO food additives series 60. pp. 352–480.
  • Williams GM, Iatropoulos MJ, Jeffrey AM, Duan JD. 2013. Methyleugenol hepatocellular cancer initiating effects in rat liver. Food Chem Toxicol. 53:187–196.
  • Willmot FC, Robertson GW. 1920. Senecio disease, or cirrhosis of the liver due to Senecio poisoning. Lancet. 196(5069):848–849.
  • Wiseman RW, Miller EC, Miller JA, Liem A. 1987. Structure-activity studies of the hepatocarcinogenicities of alkenylbenzene derivatives related to estragole and safrole on administration to preweanling male C57BL/6J x C3H/HeJ F1 mice. Cancer Res. 47(9):2275–2283.
  • Wu B, Kulkarni K, Basu S, Zhang S, Hu M. 2011. First-pass metabolism via UDP-glucuronosyltransferase: a barrier to oral bioavailability of phenolics. J Pharm Sci. 100(9):3655–3681.
  • Wu KC, McDonald PR, Liu J, Klaassen CD. 2014. Screening of natural compounds as activators of the keap1-nrf2 pathway. Planta Med. 80(1):97–104.
  • Wu X, Chen X, Huang Q, Fang D, Li G, Zhang G. 2012. Toxicity of raw and processed roots of Polygonum multiflorum. Fitoterapia. 83(3):469–475.
  • Xia N, Daiber A, Förstermann U, Li H. 2017. Antioxidant effects of resveratrol in the cardiovascular system. Br J Pharmacol. 174(12):1633–1646.
  • Xia Q, Ma L, He X, Cai L, Fu PP. 2015. 7-glutathione pyrrole adduct: a potential DNA reactive metabolite of pyrrolizidine alkaloids. Chem Res Toxicol. 28(4):615–620.
  • Xiao Y, Xue X, Wu YF, Xin GZ, Qian Y, Xie TP, Gong LK, Ren J. 2009. beta-Naphthoflavone protects mice from aristolochic acid-I-induced acute kidney injury in a CYP1A dependent mechanism. Acta Pharmacol Sin. 30(11):1559–1565.
  • Xie C, Zhong D, Chen X. 2012. Identification of the ortho-benzoquinone intermediate of 5-O-caffeoylquinic acid in vitro and in vivo: comparison of bioactivation under normal and pathological situations. Drug Metab Dispos. 40(8):1628–1640.
  • Xin Z, Wu X, Ji T, Xu B, Han Y, Sun M, Jiang S, Li T, Hu W, Deng C, Yang Y. 2019. Bakuchiol: a newly discovered warrior against organ damage. Pharmacol Res. 141:208–213.
  • Xu C, Huang MT, Shen G, Yuan X, Lin W, Khor TO, Conney AH, Kong AN. 2006. Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2. Cancer Res. 66(16):8293–8296.
  • Xu J, Yang Y. 2009. Traditional Chinese medicine in the Chinese health care system. Health Policy. 90(2-3):133–139.
  • Xu Y, Mao X, Qin B, Peng Y, Zheng J. 2018. In vitro and in vivo metabolic activation of rhein and characterization of glutathione conjugates derived from rhein. Chem Biol Interact. 283:1–9.
  • Yamano S, Tatsuno J, Gonzalez FJ. 1990. The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. Biochemistry. 29(5):1322–1329.
  • Yang B, Liu W, Chen K, Wang Z, Wang C. 2014. Metabolism of diosbulbin B in vitro and in vivo in rats: formation of reactive metabolites and human enzymes involved. Drug Metab Dispos. 42(10):1737–1750.
  • Yang M, Ruan J, Gao H, Li N, Ma J, Xue J, Ye Y, Fu PP, Wang J, Lin G. 2017. First evidence of pyrrolizidine alkaloid N-oxide-induced hepatic sinusoidal obstruction syndrome in humans. Arch Toxicol. 91(12):3913–3925.
  • Yang XW, Zhang H, Li M, Du LJ, Yang Z, Xiao SY. 2006. Studies on the alkaloid constituents of Evodia rutaecarpa (Juss) Benth var. bodinaieri (Dode) Huang and their acute toxicity in mice. J Asian Nat Prod Res. 8(8):697–703.
  • Yang YC, Yan J, Doerge DR, Chan PC, Fu PP, Chou MW. 2001. Metabolic activation of the tumorigenic pyrrolizidine alkaloid, riddelliine, leading to DNA adduct formation in vivo. Chem Res Toxicol. 14(1):101–109.
  • Yao Z, Li S, Qin Z, Hong X, Dai Y, Wu B, Ye W, Gonzalez FJ, Yao X. 2017. Characterization of human UDP-glucuronosyltransferases responsible for glucuronidation and inhibition of norbakuchinic acid, a primary metabolite of hepatotoxicity and nephrotoxicity component bakuchiol in Psoralea corylifolia L. RSC Adv. 7(83):52661–52671.
  • Yoo HH, Lee SH, Jin C, Kim DH. 2008. Mechanism-based inactivation of cytochrome P450 3A4 by methylenedioxyphenyl lignans from Acanthopanax chiisanensis. Planta Med. 74(8):822–827.
  • Yoshigae Y, Sridar C, Kent UM, Hollenberg PF. 2013. The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation. Drug Metab Dispos. 41(4):858–869.
  • You WC, Blot WJ, Chang YS, Ershow A, Yang ZT, An Q, Henderson BE, Fraumeni JF Jr, Wang TG. 1989. Allium vegetables and reduced risk of stomach cancer. J Natl Cancer Inst. 81(2):162–164.
  • Yu H, Jin H, Gong W, Wang Z, Liang H. 2013. Pharmacological actions of multi-target-directed evodiamine. Molecules. 18(2):1826–1843.
  • Yu J, Deng P, Zhong D, Chen X. 2014. Identification of amino acid and glutathione N-conjugates of toosendanin: bioactivation of the furan ring mediated by CYP3A4. Chem Res Toxicol. 27(9):1598–1609.
  • Yuan Y, Zheng J, Wang M, Li Y, Ruan J, Zhang H. 2016. Metabolic activation of rhein: insights into the potential toxicity induced by rhein-containing herbs. J Agric Food Chem. 64(28):5742–5750.
  • Yuan-Jing F, Wei W, Jian-Ping L, Yu-Xia J, Zi-Ling D. 2016. Genistein promotes the metabolic transformation of acetaminophen to glucuronic acid in human L-O2, HepG2 and Hep3b cells via the Nrf2/Keap1 pathway. Food Funct. 7(11):4683–4692.
  • Zhai J, Zhang F, Gao S, Chen L, Feng G, Yin J, Chen W. 2017. Time- and NADPH-dependent inhibition on CYP3A by gomisin A and the pharmacokinetic interactions between gomisin A and cyclophosphamide in rats. Molecules. 22(8):1298.
  • Zhang FL, He X, Zhai YR, He LN, Zhang SC, Wang LL, Yang AH, An LJ. 2015. Mechanism-based inhibition of CYPs and RMs-induced hepatoxicity by rutaecarpine. Xenobiotica. 45(11):978–989.
  • Zhang KE, Kari PH, Davis MR, Doss G, Baillie TA, Vyas KP. 2000. Metabolism of A dopamine D(4)-selective antagonist in rat, monkey, and humans: formation of A novel mercapturic acid adduct. Drug Metab Dispos. 28(6):633–642.
  • Zhang N, Seguin RP, Kunze KL, Zhang YY, Jeong H. 2013. Characterization of inhibition kinetics of (S)-warfarin hydroxylation by noscapine: implications in warfarin therapy. Drug Metab Dispos. 41(12):2114–2123.
  • Zhang S, Won YK, Ong CN, Shen HM. 2005. Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms. Curr Med Chem Anticancer Agents. 5(3):239–249.
  • Zhang X, Zhao W, Wang Y, Lu J, Chen X. 2016. The chemical constituents and bioactivities of psoralea corylifolia linn.: a review. Am J Chin Med. 44(1):35–60.
  • Zhang Y, Liu Y, Wu Z, Wang Y. 1981. A study on toxicity of bakuchiol to mice's kidney. Zhong Yao Tong Bao. 6(3):30–32.
  • Zhang Y. 2011. The molecular basis that unifies the metabolism, cellular uptake and chemopreventive activities of dietary isothiocyanates. Carcinogenesis. 33(1):2–9.
  • Zhang Z, Xu L, Cheung HY. 2014. The inhibitory effect of helenalin on telomerase activity is attributed to the alkylation of the CYS445 residue: evidence from QM/MM simulations. J Mol Graph Model. 51:97–103.
  • Zhao Y, Hellum BH, Liang A, Nilsen OG. 2015. Inhibitory mechanisms of human CYPs by three alkaloids isolated from traditional chinese herbs. Phytother Res. 29(6):825–834.
  • Zhao Y, Xia Q, Gamboa da Costa G, Yu H, Cai L, Fu PP. 2012. Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of tumor initiation. Chem Res Toxicol. 25(9):1985–1996.
  • Zheng L, Cao J, Lu D, Ji L, Peng Y, Zheng J. 2014. Imperatorin is a mechanism-based inactivator of CYP2B6. Drug Metab Dispos. 43(1):82–88.
  • Zhou B, Ye J, Yang N, Chen L, Zhuo Z, Mao L, Liu Q, Lan G, Ning J, Ge G, et al. 2018. Metabolism and pharmacokinetics of alantolactone and isoalantolactone in rats: thiol conjugation as a potential metabolic pathway. J Chromatogr B Analyt Technol Biomed Life Sci. 1072:370–378.
  • Zou L, Harkey MR, Henderson GL. 2005. Synthesis, in vitro, reactivity, and identification of 6-phenyl-3-hexen-2-one in human urine after kava-kava (Piper methysticum) ingestion. Planta Med. 71(2):142–146.

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