Protection Against Drug-Induced Liver Injuries Through Nutraceuticals via Amelioration of Nrf-2 Signaling

References

• Venmathi Maran BA, Iqbal M, Gangadaran P, Ahn B-C, Rao PV, Shah MD. Hepatoprotective potential of Malaysian medicinal plants: a review on phytochemicals, oxidative stress, and antioxidant mechanisms. Molecules. 2022;27(5):1533. doi:10.3390/molecules27051533.
   PubMed Web of Science ®Google Scholar
• Das R, Mitra S, Montakim Tareq A, Bin Emran T, Hossain MJ, Alqahtani AM, Alghazwani Y, Dhama K, Simal-Gandara J. Medicinal plants used against hepatic disorders in Bangladesh: a comprehensive review. J Ethnopharmacol. 2022;282:114588. doi:10.1016/j.jep.2021.114588.
   PubMed Web of Science ®Google Scholar
• Gomez-Lechon MJ, Lahoz A, Gombau L, Castell JV, Donato MT. In vitro evaluation of potential hepatotoxicity induced by drugs. Curr Pharm Des. 2010;16(17):1963–77. doi:10.2174/138161210791208910.
   PubMed Web of Science ®Google Scholar
• Ramachandran A, Visschers RG, Duan L, Akakpo JY, Jaeschke H. Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives. J Clin Translat Res. 2018;4(1):75. DOI 10.18053/jctres.04.201801.005
   Google Scholar
• Ntamo Y, Ziqubu K, Chellan N, Nkambule BB, Nyambuya TM, Mazibuko-Mbeje SE, Gabuza KB, Marcheggiani F, Tiano L, Dludla PV. Drug-induced liver injury: clinical evidence of N-acetyl cysteine protective effects. Oxid Med Cell Longev. 2021;2021:1–12. doi:10.1155/2021/3320325.
   Google Scholar
• Mohi-Ud-Din R, Mir RH, Sawhney G, Dar MA, Bhat ZA. Possible pathways of hepatotoxicity caused by chemical agents. Curr Drug Metab. 2019;20(11):867–79. doi:10.2174/1389200220666191105121653.
   PubMed Web of Science ®Google Scholar
• Adhikari B, Marasini BP, Rayamajhee B, Bhattarai BR, Lamichhane G, Khadayat K, Adhikari A, Khanal S, Parajuli N. Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID‐19: a review. Phytother Res. 2021;35(3):1298–312. doi:10.1002/ptr.6893.
   PubMed Web of Science ®Google Scholar
• Petrovska BB . Historical review of medicinal plants’ usage. Pharmacogn Rev. 2012;6(11):1–5. doi:10.4103/0973-7847.95849.
   PubMedGoogle Scholar
• Ali SS, Kasoju N, Luthra A, Singh A, Sharanabasava H, Sahu A, Bora U. Indian medicinal herbs as sources of antioxidants. Food Res Int. 2008;41(1):1–15. doi:10.1016/j.foodres.2007.10.001.
   Web of Science ®Google Scholar
• Benny NR, Sonia NS, Sreekala GS. Hepatoprotective medicinal plants traditional knowledge to scientific evidences: a review. J Pharmacogn Phytochem. 2021;10:285–8.
   Google Scholar
• Rastogi S. Ayurveda education in India: addressing the human resource barriers to optimize the delivery. J Ayurveda Integr Med. 2021;12(2):403–7. doi:10.1016/j.jaim.2020.04.003.
   PubMed Web of Science ®Google Scholar
• Doberer D, A, Haschemi M, Andreas T, C, Zapf B, Clive M, Jeitler H, Heinzl O, Wagner M, Wolzt, M, Bilban . Haem arginate infusion stimulates haem oxygenase-1 expression in healthy subjects. Br J Pharmacol. 2010;161(8):1751–62. doi:10.1111/j.1476-5381.2010.00990.x.
   PubMed Web of Science ®Google Scholar
• Farombi EO, Surh YJ. Heme oxygenase-1 as a potential therapeutic target for hepatoprotection. J Biochem Mol Biol. 2006;39(5):479–91. doi:10.5483/bmbrep.2006.39.5.479.
   PubMedGoogle Scholar
• Ahmed SMU, Luo L, Namani A, Wang XJ, Tang X. Nrf2 signaling pathway: pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis. 2017;1863(2):585–97. doi:10.1016/j.bbadis.2016.11.005.
   PubMed Web of Science ®Google Scholar
• Senger DR, Li D, Jaminet S-C, Cao S. Activation of the Nrf2 cell defense pathway by ancient foods: disease prevention by important molecules and microbes lost from the modern western diet. PLoS One. 2016;11(2):e0148042. doi:10.1371/journal.pone.0148042.
   PubMed Web of Science ®Google Scholar
• Rasool MK, Sabina EP, Ramya SR, Preety P, Patel S, Mandal N, Mishra PP, Samuel J. Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. J Pharm Pharmacol. 2010;62(5):638–43. doi:10.1211/jpp.62.05.0012.
   PubMed Web of Science ®Google Scholar
• Radan M, Dianat M, Badavi M, Mard SA, Bayati V, Goudarzi G. In vivo and in vitro evidence for the involvement of Nrf2-antioxidant response element signaling pathway in the inflammation and oxidative stress induced by particulate matter (PM10): the effective role of gallic acid. Free Radic Res. 2019;53(2):210–25. doi:10.1080/10715762.2018.1563689.
   PubMed Web of Science ®Google Scholar
• Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009;284(20):13291–5. doi:10.1074/jbc.R900010200.
   PubMed Web of Science ®Google Scholar
• Singh MP, Kwak G-H, Kim KY, Kim H-Y. Methionine sulfoxide reductase A protects hepatocytes against acetaminophen-induced toxicity via regulation of thioredoxin reductase 1 expression. Biochem Biophys Res Commun. 2017;487(3):695–701. doi:10.1016/j.bbrc.2017.04.119.
   PubMed Web of Science ®Google Scholar
• Nitti M, Piras S, Marinari U, Moretta L, Pronzato M, Furfaro A. HO-1 induction in cancer progression: a matter of cell adaptation. Antioxidants. 2017;6(2):29. doi:10.3390/antiox6020029.
   Web of Science ®Google Scholar
• McConnachie LA, Mohar I, Hudson FN, Ware CB, Ladiges WC, Fernandez C, Chatterton-Kirchmeier S, White CC, Pierce RH, Kavanagh TJ. Glutamate cysteine ligase modifier subunit deficiency and gender as determinants of acetaminophen-induced hepatotoxicity in mice. Toxicol Sci. 2007;99(2):628–36. doi:10.1093/toxsci/kfm165.
   PubMed Web of Science ®Google Scholar
• Kay HY, Kim YW, Ryu DH, Sung SH, Hwang SJ, Kim SG . Nrf2-mediated liver protection by sauchinone, an antioxidant lignan, from acetaminophen toxicity through the PKCδ-GSK3β pathway. Br J Pharmacol. 2011;163(8):1653–65. [DOI https://bpspubs.onlinelibrary.wiley.com/journal/14765381] doi:10.1111/j.1476-5381.2010.01095.x.
   PubMed Web of Science ®Google Scholar
• Ajiboye TO, Salau AK, Yakubu MT, Oladiji AT, Akanji MA, Okogun JI. Acetaminophen perturbed redox homeostasis in Wistar rat liver: protective role of aqueous Pterocarpus osun leaf extract. Drug Chem Toxicol. 2010;33(1):77–87. doi:10.3109/01480540903170746.
   PubMed Web of Science ®Google Scholar
• Cabrera C, Artacho R, Giménez R . Beneficial effects of green tea—a review. J Am Coll Nutr. 2006;25(2):79–99. doi:10.1080/07315724.2006.10719518.
   PubMed Web of Science ®Google Scholar
• Waza AA, Hamid Z, Ali S, Bhat SA, Bhat MA. A review on heme oxygenase-1 induction: is it a necessary evil. Inflamm Res. 2018;67(7):579–88. doi:10.1007/s00011-018-1151-x.
   PubMed Web of Science ®Google Scholar
• Dhiman A, Nanda A, Ahmad S. A recent update in research on the antihepatotoxic potential of medicinal plants. Zhong Xi Yi Jie He Xue Bao. 2012;10(2):117–27. doi:10.3736/jcim20120201.
   PubMedGoogle Scholar
• Kohlroser J, Mathai J, Reichheld J, Banner BF, Bonkovsky HL. Hepatotoxicity due to troglitazone: report of two cases and review of adverse events reported to the United States Food and Drug Administration. Am J Gastroenterol. 2000;95(1):272–6. doi:10.1111/j.1572-0241.2000.01707.x.
   PubMed Web of Science ®Google Scholar
• Donato MT, Tolosa L. High-content screening for the detection of drug-induced oxidative stress in liver cells. Antioxidants. 2021;10(1):106. doi:10.3390/antiox10010106.
   Web of Science ®Google Scholar
• Lynch T, Neff AP. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Family Phys. 2007;76(3):391–6.
   PubMed Web of Science ®Google Scholar
• Cover C, Mansouri A, Knight TR, Bajt ML, Lemasters JJ, Pessayre D, Jaeschke H. Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity. J Pharmacol Exp Ther. 2005;315(2):879–87. doi:10.1124/jpet.105.088898.
   PubMed Web of Science ®Google Scholar
• Kim DE, Jang M-J, Kim YR, Lee J-Y, Cho EB, Kim E, Kim Y, Kim MY, Jeong W-I, Kim S, et al. Prediction of drug-induced immune-mediated hepatotoxicity using hepatocyte-like cells derived from human embryonic stem cells. Toxicology. 2017;387:1–9. doi:10.1016/j.tox.2017.06.005.
   PubMed Web of Science ®Google Scholar
• Podsiedlik M, Markowicz-Piasecka M, Sikora J. Erythrocytes as model cells for biocompatibility assessment, cytotoxicity screening of xenobiotics and drug delivery. Chem Biol Interact. 2020;332:109305. doi:10.1016/j.cbi.2020.109305.
   PubMed Web of Science ®Google Scholar
• Xiao F, Ai G, Yan W, Wan X, Luo X, Ning Q. Intrahepatic recruitment of cytotoxic NK cells contributes to autoimmune hepatitis progression. Cell Immunol. 2018;327:13–20. doi:10.1016/j.cellimm.2017.12.008.
   PubMed Web of Science ®Google Scholar
• Holt MP, Ju C. Mechanisms of drug-induced liver injury. AAPS J. 2006;8(1):E48–54. doi:10.1208/aapsj080106.
   PubMed Web of Science ®Google Scholar
• Li S, Tan H-Y, Wang N, Zhang Z-J, Lao L, Wong C-W, Feng Y. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci. 2015;16(11):26087–124. doi:10.3390/ijms161125942.
   PubMed Web of Science ®Google Scholar
• Saad KM, Shaker ME, Shaaban AA, Abdelrahman RS, Said E. The c-Met inhibitor capmatinib alleviates acetaminophen-induced hepatotoxicity. Int Immunopharmacol. 2020;81:106292. doi:10.1016/j.intimp.2020.106292.
   PubMed Web of Science ®Google Scholar
• Mao G, Kraus GA, Kim I, Spurlock ME, Bailey TB, Beitz DC. Effect of a mitochondria-targeted vitamin E derivative on mitochondrial alteration and systemic oxidative stress in mice. Br J Nutr. 2011;106(1):87–95. doi:10.1017/S0007114510005830.
   PubMed Web of Science ®Google Scholar
• Tan YQ, Zhang X, Zhang S, Zhu T, Garg M, Lobie PE, Pandey V. Mitochondria: the metabolic switch of cellular oncogenic transformation. Biochim Biophys Acta Rev Cancer. 2021;1876(1):188534. doi:10.1016/j.bbcan.2021.188534.
   PubMed Web of Science ®Google Scholar
• Wang N, Wang H, Zhang J, Ji X, Su H, Liu J, Wang J, Zhao W. Endogenous peroxynitrite activated fluorescent probe for revealing anti‐tuberculosis drug-induced hepatotoxicity. Chinese Chem Lett. 2022;33(3):1584–8. doi:10.1016/j.cclet.2021.09.046.
   Web of Science ®Google Scholar
• Zhong X, Zhang Z, Shen H, Xiong Y, Shah YM, Liu Y, Fan X, Rui L . Hepatic NF-κB-inducing kinase and inhibitor of NF-κB kinase subunit α promote liver oxidative stress, ferroptosis, and liver injury. Hepatol Commun. 2021;5(10):1704–20. doi:10.1002/hep4.1757.
   PubMed Web of Science ®Google Scholar
• Abou Seif HS. Physiological changes due to hepatotoxicity and the protective role of some medicinal plants. Beni-Suef Univ J Basic Appl Sci. 2016;5(2):134–46. doi:10.1016/j.bjbas.2016.03.004.
   Google Scholar
• Han D, Dara L, Win S, Than TA, Yuan L, Abbasi SQ, Liu Z-X, Kaplowitz N. Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria. Trends Pharmacol Sci. 2013;34(4):243–53. doi:10.1016/j.tips.2013.01.009.
   PubMed Web of Science ®Google Scholar
• Ishida Y, Kondo T, Ohshima T, Fujiwara H, Iwakura Y, Mukaida N . A pivotal involvement of IFN-gamma in the pathogenesis of acetaminophen-induced acute liver injury. FASEB J. 2002;16(10):1227–36. doi:10.1096/fj.02-0046com.
   PubMed Web of Science ®Google Scholar
• Cao J, Mi Y, Shi C, Bian Y, Huang C, Ye Z, Liu L, Miao L. First-line anti-tuberculosis drugs induce hepatotoxicity: a novel mechanism based on a urinary metabolomics platform. Biochem Biophys Res Commun. 2018;497(2):485–91. doi:10.1016/j.bbrc.2018.02.030.
   PubMed Web of Science ®Google Scholar
• Zoubek ME, González-Jimenez A, Medina-Cáliz I, Robles-Díaz M, Hernandez N, Romero-Gómez M, Bessone F, Hallal H, Cubero FJ, Lucena MI, et al. High prevalence of Ibuprofen drug-induced liver injury in Spanish and Latin-American registries. Clin Gastroenterol Hepatol. 2018;16(2):292–4. doi:10.1016/j.cgh.2017.07.037.
   PubMed Web of Science ®Google Scholar
• Masubuchi Y, Suda C, Horie T. Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice. J Hepatol. 2005;42(1):110–6. doi:10.1016/j.jhep.2004.09.015.
   PubMed Web of Science ®Google Scholar
• Villanueva-Paz M, Morán L, López-Alcántara N, Freixo C, Andrade RJ, Isabel Lucena M, Cubero FJ. Oxidative stress in drug-induced liver injury (DILI): from mechanisms to biomarkers for use in clinical practice. Antioxidants. 2021;10(3):390. doi:10.3390/antiox10030390.
   Web of Science ®Google Scholar
• Gallot YS, Bohnert KR. Confounding roles of ER stress and the unfolded protein response in skeletal muscle atrophy. IJMS. 2021;22(5):2567. doi:10.3390/ijms22052567.
   Google Scholar
• Wendel A, Feuerstein S, Konz K-H. Acute paracetamol intoxication of starved mice leads to lipid peroxidation in vivo. Biochem Pharmacol. 1979;28(13):2051–5. [DOI ]. doi:10.1016/0006-2952(79)90223-5.
   PubMed Web of Science ®Google Scholar
• Shen G, Kong A. Nrf2 plays an important role in coordinated regulation of Phase II drug metabolism enzymes and Phase III drug transporters. Biopharm Drug Dispos. 2009;30(7):345–55. doi:10.1002/bdd.680.
   PubMed Web of Science ®Google Scholar
• Prasad B, Bhatt DK, Johnson K, Chapa R, Chu X, Salphati L, Xiao G, Lee C, Hop CECA, Mathias A, et al. Abundance of phase 1 and 2 drug-metabolizing enzymes in alcoholic and hepatitis C cirrhotic livers: a quantitative targeted proteomics study. Drug Metab Dispos. 2018;46(7):943–52. doi:10.1124/dmd.118.080523.
   PubMed Web of Science ®Google Scholar
• Forrester LM, Henderson CJ, Glancey MJ, Back DJ, Park BK, Ball SE, Kitteringham NR, McLaren AW, Miles JS, Skett P, et al. Relative expression of cytochrome P 450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics. Biochem J. 1992;281(2):359–68. doi:10.1042/bj2810359.
   PubMedGoogle Scholar
• Guengerich FP. Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J. 2006;8(1):E101–11. doi:10.1208/aapsj080112.
   PubMed Web of Science ®Google Scholar
• Deng J, Zhao L, Zhang N-Y, Karrow NA, Krumm CS, Qi D-S, Sun L-H. Aflatoxin B1 metabolism: regulation by phase I and II metabolizing enzymes and chemoprotective agents. Mutat Res Rev Mutat Res. 2018;778:79–89. doi:10.1016/j.mrrev.2018.10.002.
   PubMed Web of Science ®Google Scholar
• Asadi-Samani M, Kafash-Farkhad N, Azimi N, Fasihi A, Alinia-Ahandani E, Rafieian-Kopaei M. Medicinal plants with hepatoprotective activity in Iranian folk medicine. Asian Pacific J Trop Biomed. 2015;5(2):146–57. doi:10.1016/S2221-1691(15)30159-3.
   Google Scholar
• Shin DH, Cho HJ, Park SH, Jeong SW, Park C-W, Han K, Chung YB. HPLC analysis of ferulic acid and its pharmacokinetics after intravenous bolus administration in rats. J Biomed Transl Res. 2016;17(1):1–7. doi:10.12729/jbtr.2016.17.1.001.
   Google Scholar
• Lin X, Bai D, Wei Z, Zhang Y, Huang Y, Deng H, Huang X . Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway. PLoS One. 2019;14(5):e0216711. doi:10.1371/journal.pone.0216711.
   PubMed Web of Science ®Google Scholar
• Gutierres VO, Campos ML, Arcaro CA, Assis RP, Baldan-Cimatti HM, Peccinini RG, Paula-Gomes S, Kettelhut IC, Baviera AM, Brunetti IL. Curcumin pharmacokinetic and pharmacodynamic evidences in streptozotocin-diabetic rats support the antidiabetic activity to be via metabolite (s). Evid-Based Complement Altern Med. 2015;2015:1–13. doi:10.1155/2015/678218.
   Web of Science ®Google Scholar
• Liu X-W, Yang J-L, Niu W, Jia W-W, Olaleye OE, Wen Q, Duan X-N, Huang Y-H, Wang F-Q, Du F-F, et al. Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity. Acta Pharmacol Sin. 2018;39(12):1935–46. DOI: 10.1038/s41401-018-0086-7
   PubMed Web of Science ®Google Scholar
• Ou-yang Z, Cao X, Wei Y, Zhang W-W-Q, Zhao M, Duan J-a. Pharmacokinetic study of rutin and quercetin in rats after oral administration of total flavones of mulberry leaf extract. Rev Brasileira Farmacogn. 2013;23(5):776–82.doi:10.1590/S0102-695X2013000500009.
   Google Scholar
• Ma J-Q, Ding J, Zhang L, Liu C-M. Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway. Clin Res Hepatol Gastroenterol. 2015;39(2):188–97. doi:10.1016/j.clinre.2014.09.007.
   PubMed Web of Science ®Google Scholar
• Zhu Z, Qian Z, Yan Z, Zhao C, Wang H, Ying G. A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors. Int J Nanomedicine. 2013;8:129–36. doi:10.2147/IJN.S38271.
   PubMed Web of Science ®Google Scholar
• Lv Z, Wu W, Ge S, Jia R, Lin T, Yuan Y, Kuang H, Yang B, Wu L, Wei J, et al. Naringin protects against perfluorooctane sulfonate-induced liver injury by modulating NRF2 and NF-κB in mice. Int Immunopharmacol. 2018;65:140–7. doi:10.1016/j.intimp.2018.09.019.
   PubMed Web of Science ®Google Scholar
• Bai Y, Peng W, Yang C, Zou W, Liu M, Wu H, Fan L, Li P, Zeng X, Su W. Pharmacokinetics and metabolism of naringin and active metabolite naringenin in rats, dogs, humans, and the differences between species. Front Pharmacol. 2020;11:364.doi:10.3389/fphar.2020.00364.
   PubMed Web of Science ®Google Scholar
• Singh S, Kumar Singh D, Meena A, Dubey V, Masood N, Luqman S. Rutin protects t-butyl hydroperoxide-induced oxidative impairment via modulating the Nrf2 and iNOS activity. Phytomedicine. 2019;55:92–104. doi:10.1016/j.phymed.2018.07.009.
   PubMed Web of Science ®Google Scholar
• Krajka-Kuźniak V, Paluszczak J, Baer-Dubowska W. Xanthohumol induces phase II enzymes via Nrf2 in human hepatocytes in vitro. Toxicol Vitro. 2013;27(1):149–56. doi:10.1016/j.tiv.2012.10.008.
   PubMed Web of Science ®Google Scholar
• Legette L, L, Ma RL, Reed CL, Miranda JM, Christensen R, RodriguezProteau, JF, Stevens. Pharmacokinetics of xanthohumol and metabolites in rats after oral and intravenous administration. Mol Nutr Food Res. 2012;56(3):466–74. doi:10.1002/mnfr.201100554.
   PubMed Web of Science ®Google Scholar
• Lu Q, Tan S, Gu W, Li F, Hua W, Zhang S, Chen F, Tang L. Phytochemical composition, isolation and hepatoprotective activity of active fraction from Veronica ciliata against acetaminophen-induced acute liver injury via p62-Keap1-Nrf2 signaling pathway. J Ethnopharmacol. 2019;243:112089. doi:10.1016/j.jep.2019.112089.
   PubMed Web of Science ®Google Scholar
• Chen C, Yin Q, Tian J, Gao X, Qin X, Du G, Zhou Y. Studies on the changes of pharmacokinetics behaviors of phytochemicals and the influence on endogenous metabolites after the combination of radix Bupleuri and Radix Paeoniae Alba based on multi-component pharmacokinetics and metabolomics. Front Pharmacol. 2021;12:222. doi:10.3389/fphar.2021.630970.
   Web of Science ®Google Scholar
• Wang X, Liu J, Zhang X, Zhao S, Zou K, Xie J, Wang X, Liu C, Wang J, Wang Y . Seabuckthorn berry polysaccharide extracts protect against acetaminophen induced hepatotoxicity in mice via activating the Nrf-2/HO-1-SOD-2 signaling pathway. Phytomedicine. 2018;38:90–7. doi:10.1016/j.phymed.2017.11.007.
   PubMed Web of Science ®Google Scholar
• Antunes-Ricardo M, Rodríguez-Rodríguez C, Gutiérrez-Uribe JA, Cepeda-Cañedo E, Serna-Saldívar SO. Bioaccessibility, intestinal permeability and plasma stability of isorhamnetin glycosides from Opuntia ficus-indica (L.). IJMS. 2017;18(8):1816. doi:10.3390/ijms18081816.
   Google Scholar
• Kumar KS, Chu F-H, Hsieh H-W, Liao J-W, Li W-H, Lin JC-C, Shaw J-F, Wang S-Y. Antroquinonol from ethanolic extract of mycelium of Antrodia cinnamomea protects hepatic cells from ethanol-induced oxidative stress through Nrf-2 activation. J Ethnopharmacol. 2011;136(1):168–77. doi:10.1016/j.jep.2011.04.030.
   PubMed Web of Science ®Google Scholar
• Zhou R-J, Ye H, Wang F, Wang J-L, Xie M-L. Apigenin inhibits d-galactosamine/LPS-induced liver injury through upregulation of hepatic Nrf-2 and PPARγ expressions in mice. Biochem Biophys Res Commun. 2017;493(1):625–30. doi:10.1016/j.bbrc.2017.08.141.
   PubMed Web of Science ®Google Scholar
• DeRango-Adem EF, Blay J. Does oral apigenin have real potential for a therapeutic effect in the context of human gastrointestinal and other cancers? Front Pharmacol. 2021;12:1196. doi:10.3389/fphar.2021.681477.
   Google Scholar
• El-Emam SZ, Soubh AA, Al-Mokaddem AK, Abo El-Ella DM. Geraniol activates Nrf-2/HO-1 signaling pathway mediating protection against oxidative stress-induced apoptosis in hepatic ischemia-reperfusion injury. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(10):1849–58. doi:10.1007/s00210-020-01887-1.
   PubMed Web of Science ®Google Scholar
• Pavan B, Dalpiaz A, Marani L, Beggiato S, Ferraro L, Canistro D, Paolini M, Vivarelli F, Valerii MC, Comparone A, et al. Geraniol pharmacokinetics, bioavailability and its multiple effects on the liver antioxidant and xenobiotic-metabolizing enzymes. Front Pharmacol. 2018;9:18. doi:10.3389/fphar.2018.00018.
   PubMed Web of Science ®Google Scholar
• Li A, Zhuang X, Zhao W, Ji H, Li X, Zhong X, Fang L, Wang F, Guo F. Bilobalide ameliorates carbon tetrachloride-induced oxidative damage in Hep G2 cells by the induction of Nrf 2-dependent HO-1 expression through PI3K/Akt and P 38 pathways. Int J Clin Exp Med. 2017;10(4):6115–25.
   Web of Science ®Google Scholar
• Manipuri P, Indala R, Jagaralmudi A, Kumar KR. Hepatoprotective effect of Inula racemosa on hepatic ischemia/reperfusion-induced injury in rats. J Bioanal Biomed. 2013;05(02):022–7. doi:10.4172/1948-593X.1000076.
   Google Scholar
• Wang Z, Geng L, Chen Z, Lin B, Zhang M, Zheng S. In vivo therapeutic potential of Inula racemosa in hepatic ischemia-reperfusion injury following orthotopic liver transplantation in male albino rats. AMB Expr. 2017;7(1):1–10. doi:10.1186/s13568-017-0511-1.
   PubMedGoogle Scholar
• Kim DY, Choi BY. Costunolide—a bioactive sesquiterpene lactone with diverse therapeutic potential. IJMS. 2019;20(12):2926. doi:10.3390/ijms20122926.
   Google Scholar
• Huang W, Wang Y, Jiang X, Sun Y, Zhao Z, Li S. Protective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao against acetaminophen-induced liver injury by inhibiting oxidative stress and inflammation in mice. Molecules. 2017;22(10):1781. doi:10.3390/molecules22101781.
   PubMed Web of Science ®Google Scholar
• Yang L-L, Xiao N, Li X-W, Fan Y, Alolga RN, Sun X-Y, Wang S-L, Li P, Qi L-W. Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS. Sci Rep. 2016;6(1):1–9. doi:10.1038/srep35460.
   PubMedGoogle Scholar
• Abdel-Rahman RF, Fayed HM, Ogaly HA, Hussein RA, Raslan M. Phytoconstituents of Sansevieria suffruticosa NE Br. leaves and its hepatoprotective effect via activation of the NRF2/ARE signaling pathway in an experimentally induced liver fibrosis rat model. Chem Biodivers. 2022;19(4). doi:10.1002/cbdv.202100960.
   PubMed Web of Science ®Google Scholar
• Miao L, Yang Y, Li Z, Fang Z, Zhang Y, Han C-C. Ginsenoside Rb2: a review of pharmacokinetics and pharmacological effects. J Ginseng Res. 2022;46(2):206–13. doi:10.1016/j.jgr.2021.11.007.
   PubMed Web of Science ®Google Scholar
• Mansour DF, Abdallah HM, Ibrahim BM, Hegazy RR, Esmail RS, Abdel-Salam LO . The carcinogenic agent diethylnitrosamine induces early oxidative stress, inflammation and proliferation in rat liver, stomach and colon: protective effect of ginger extract. Asian Pac J Cancer Prev. 2019;20(8):2551–61. doi:10.31557/APJCP.2019.20.8.2551.
   PubMedGoogle Scholar
• Zick SM, Ruffin MT, Djuric Z, Normolle D, Brenner DE. Quantitation of 6-, 8-and 10-gingerols and 6-shogaol in human plasma by high-performance liquid chromatography with electrochemical detection. Int J Biomed Sci. 2010;6(3):233–40.
   PubMedGoogle Scholar
• Kanwal HA, Majeed W, Awan AM, Aslam B. and ROS Polyphenols from green tea revert CCl4-induced liver oxidative stress and inflammation associated with high-fat diet by activation of NRF-2 and TIMP-1 pathways to neutralize. 2022. [doi:10.21203/rs.3.rs-1414824/v1.]
   Google Scholar
• Janle EM, Morré DM, James Morré D, Zhou Q, Zhu Y. Pharmacokinetics of green tea catechins in extract and sustained-release preparations. J Diet Suppl. 2008;5(3):248–63. doi:10.1080/19390210802414279.
   PubMedGoogle Scholar
• Motawi TK, Ahmed SA, El-Boghdady NA, Metwally NS, Nasr NN. Impact of betanin against paracetamol and diclofenac induced hepato-renal damage in rats. Biomarkers. 2020;25(1):86–93. doi:10.1080/1354750X.2019.1697365.
   PubMed Web of Science ®Google Scholar
• Hussein F, Ahmed J. Effect of Nigella sativa (black cumin), vitamin E and their combination on metoprolol induced hepatotoxicity in rabbits. Ind J Forensic Med Toxicol. 2021;15(3):1059–1065.
   Google Scholar
• Madadi E, Mazloum-Ravasan S, Yu JS, Ha JW, Hamishehkar H, Kim KH. Therapeutic application of betalains: a review. Plants. 2020;9(9):1219. doi:10.3390/plants9091219.
   Google Scholar
• Shahrzad S, Aoyagi K, Winter A, Koyama A, Bitsch I. Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans. J Nutr. 2001;131(4):1207–10. doi:10.1093/jn/131.4.1207.
   PubMed Web of Science ®Google Scholar
• Wei X, Luo C, He Y, Huang H, Ran F, Liao W, Tan P, Fan S, Cheng Y, Zhang D, et al. Hepatoprotective effects of different extracts from Triphala against CCl4-induced acute liver injury in mice. Front Pharmacol. 2021;12:664607. doi:10.3389/fphar.2021.664607.
   PubMed Web of Science ®Google Scholar
• Chu KO, Pang CC. Pharmacokinetics and disposition of green tea catechins. In: Malangu N, editor. Pharmacokinetics and adverse effects of drugs: mechanisms and risks factors. Vol. 17. UK: IntechOpen; 2018.17–34.
   Google Scholar
• Jia R, Gu Z, He Q, Du J, Cao L, Jeney G, Xu P, Yin G. Anti-oxidative, anti-inflammatory and hepatoprotective effects of Radix Bupleuri extract against oxidative damage in tilapia (Oreochromis niloticus) via Nrf2 and TLRs signaling pathway. Fish Shellfish Immunol. 2019;93:395–405. doi:10.1016/j.fsi.2019.07.080.
   PubMed Web of Science ®Google Scholar
• Lin G, Luo D, Liu J, Wu X, Chen J, Huang Q, Su L, Zeng L, Wang H, Su Z. Hepatoprotective effect of polysaccharides isolated from Dendrobium officinale against acetaminophen-induced liver injury in mice via regulation of the Nrf2-Keap1 signaling pathway. Oxid Med Cell Longev. 2018;2018:6962439. doi:10.1155/2018/6962439.
   PubMed Web of Science ®Google Scholar
• Feng X-H, Xu H-Y, Wang J-Y, Duan S, Wang Y-C, Ma C-M. In vivo hepatoprotective activity and the underlying mechanism of chebulinic acid from Terminalia chebula fruit. Phytomedicine. 2021;83:153479. doi:10.1016/j.phymed.2021.153479.
   PubMed Web of Science ®Google Scholar
• Lei F, Xing D-M, Xiang L, Zhao Y-N, Wang W, Zhang L-J, Du L-J. Pharmacokinetic study of ellagic acid in rat after oral administration of pomegranate leaf extract. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;796(1):189–94. doi:10.1016/s1570-0232(03)00610-x.
   PubMed Web of Science ®Google Scholar
• Lu Q, Gu W, Luo C, Wang L, Hua W, Sun Y, Tang L. Phytochemical characterization and hepatoprotective effect of active fragment from Adhatoda vasica Nees. against tert-butyl hydroperoxide induced oxidative impairment via activating AMPK/p62/Nrf2 pathway. J Ethnopharmacol. 2021;266:113454. doi:10.1016/j.jep.2020.113454.
   PubMed Web of Science ®Google Scholar
• Yang S-Y, Pyo MC, Nam M-H, Lee K-W. ERK/Nrf2 pathway activation by caffeic acid in HepG2 cells alleviates its hepatocellular damage caused by t-butyl hydroperoxide-induced oxidative stress. BMC Complement Altern Med. 2019;19(1):1–13. doi:10.1186/s12906-019-2551-3.
   PubMedGoogle Scholar
• Praditya D, Kirchhoff L, Brüning J, Rachmawati H, Steinmann J, Steinmann E. Anti-infective properties of the golden spice curcumin. Front Microbiol. 2019;10:912. doi:10.3389/fmicb.2019.00912.
   PubMed Web of Science ®Google Scholar
• Mohammed SA, Eldeeb HM, Mohammed HA, Al-Omar MS, Almahmoud SA, El-Readi MZ, Ragab EA, Sulaiman GM, Aly MS, Khan RA. Roles of Suaeda vermiculata aqueous-ethanolic extract, its subsequent fractions, and the isolated compounds in hepatoprotection against paracetamol-induced toxicity as compared to silymarin. Oxid Med Cell Longev. 2021;2021:1–10. doi:10.1155/2021/6174897.
   Web of Science ®Google Scholar
• Anand U, Keeya Tudu C, Nandy S, Sunita K, Tripathi V, Loake GJ, Dey A, Proćków J . Ethnodermatological use of medicinal plants in India: from ayurvedic formulations to clinical perspectives—a review. J Ethnopharmacol. 2022;284:114744. doi:10.1016/j.jep.2021.114744.
   PubMed Web of Science ®Google Scholar
• Polimati H, Pragada RR, Thuan NH, Bharadwaj Tatipamula V. Hepatoprotective potential of bioflavonoids. Stud Nat Prod Chem. 2022;72:259–85. [doi:10.1016/B978-0-12-823944-5.00014-4.]
   Google Scholar
• El-Readi MZ, Al-Abd AM, Althubiti MA, Almaimani RA, Al-Amoodi HS, Ashour ML, Wink M, Eid SY. Multiple molecular mechanisms to overcome multidrug resistance in cancer by natural secondary metabolites. Front Pharmacol. 2021;12:942. doi:10.3389/fphar.2021.658513.
   Web of Science ®Google Scholar
• Singh MP, Kim KY, Kim H-Y. Methionine sulfoxide reductase A deficiency exacerbates acute liver injury induced by acetaminophen. Biochem Biophys Res Commun. 2017;484(1):189–94. doi:10.1016/j.bbrc.2017.01.025.
   PubMed Web of Science ®Google Scholar
• Verma S, Singh SP. Current and future status of herbal medicines. Vet World. 2008;2(2):347. doi:10.5455/vetworld.2008.347-350.
   Google Scholar
• Sandur SK, Ichikawa H, Pandey MK, Kunnumakkara AB, Sung B, Sethi G, Aggarwal BB. Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane). Free Radic Biol Med. 2007;43(4):568–80. doi:10.1016/j.freeradbiomed.2007.05.009.
   PubMed Web of Science ®Google Scholar
• David Waterbury L, Silliman D, Jolas T. Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin. 2006;22(6):1133–40. doi:10.1185/030079906X112471.
   PubMed Web of Science ®Google Scholar
• Lei S, Gu R, Ma X. Clinical perspectives of isoniazid-induced liver injury. Liver Res. 2021;5(2):45–52. doi:10.1016/j.livres.2021.02.001.
   Google Scholar
• Satvati M, Salehi-Vanani N, Nouri A, Heidarian E. Protective effects of N-acetyl cysteine against oxidative stress in ibuprofen-induced hepatotoxicity in rats. Comp Clin Pathol. 2022;31(2):293–301. doi:10.1007/s00580-022-03332-6.
   Google Scholar
• Rousta A-M, Mirahmadi S-M-S, Shahmohammadi A, Mehrabi Z, Fallah S, Baluchnejadmojarad T, Roghani M. Therapeutic potential of isorhamnetin following acetaminophen-induced hepatotoxicity through targeting NLRP3/NF-κB/Nrf2. Drug Res (Stuttg). 2022;72(05):245–54. doi:10.1055/a-1792-2678.
   PubMed Web of Science ®Google Scholar
• Jamshed N, Raza I, Rasheed A, Jamshed N, Akhtar L, Rashid N. Impact of aqueous neem leave extract on erythromycin induced hepatotoxicity. PAFMJ. 2022;72(1):235–9.
   Google Scholar
• Castelo-Branco C, Del Pino M. Hepatotoxicity during low-dose flutamide treatment for hirsutism. Gynecol Endocrinol. 2009;25(7):419–22. doi:10.1080/09513590902730754.
   PubMed Web of Science ®Google Scholar
• Leong RW, Gearry RB, Sparrow MP. Thiopurine hepatotoxicity in inflammatory bowel disease: the role for adding allopurinol. Expert Opin Drug Saf. 2008;7(5):607–16. doi:10.1517/14740338.7.5.607.
   PubMed Web of Science ®Google Scholar
• Gupta A, Kumar R, Ganguly R, Singh AK, Kumar Rana H, Pandey AK. Antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica and its bioactive component ellagic acid against diclofenac induced oxidative stress and hepatotoxicity. Toxicol Rep. 2021;8:44–52. doi:10.1016/j.toxrep.2020.12.010.
   PubMed Web of Science ®Google Scholar
• Patocka J, Wu Q, Nepovimova E, Kuca K . Phenytoin—An anti-seizure drug: overview of its chemistry, pharmacology and toxicology. Food Chem Toxicol. 2020;142:111393. doi:10.1016/j.fct.2020.111393.
   PubMed Web of Science ®Google Scholar
• Bai Z, Jia K, Chen G, Liao X, Cao Z, Zhao Y, Zhang C, Lu H. Carbamazepine induces hepatotoxicity in zebrafish by inhibition of the Wnt/β-catenin signaling pathway. Environ Pollut. 2021;276:116688. doi:10.1016/j.envpol.2021.116688.
   PubMed Web of Science ®Google Scholar
• Ahmad MH, Fatima M, Hossain M, Mondal AC. Evaluation of naproxen-induced oxidative stress, hepatotoxicity and in-vivo genotoxicity in male Wistar rats. J Pharmaceut Anal. 2018;8(6):400–6. doi:10.1016/j.jpha.2018.04.002.
   PubMed Web of Science ®Google Scholar
• Iqbal MO, Manzoor M, Mumtaz A, Riaz R, Arshad S, Khan IA, Javaid U, Manzoor Z, Munawar SH, Andleeb S, et al. Evaluation of the hepatoprotective activity of hydroalcoholic extract of Alhagi camelorum against valproic acid-induced hepatotoxicity in rats. Biomed Pharmacother. 2022;150:112953. doi:10.1016/j.biopha.2022.112953.
   PubMed Web of Science ®Google Scholar
• Slim R, Salem CB, Hmouda H, Bouraoui K . Hepatotoxicity of alpha-methyldopa in pregnancy. J Clin Pharm Ther. 2010;35(3):361–3. [DOI doi:10.1111/j.1365-2710.2009.01078.x.
   PubMed Web of Science ®Google Scholar
• Altay D, Pamukçu Ö, Baykan A, Üzüm K, Arslan D. Aspirin-induced hepatotoxicity and anemia in children with acute rheumatic fever. Turk J Pediatr. 2021;63(2):193–9. doi:10.24953/turkjped.2021.02.002.
   PubMed Web of Science ®Google Scholar
• Akindele AJ, Oludadepo GO, Amagon KI, Singh D, Osiagwu DD. Protective effect of carvedilol alone and coadministered with diltiazem and prednisolone on doxorubicin and 5‐fluorouracil‐induced hepatotoxicity and nephrotoxicity in rats. Pharmacol Res Perspect. 2018;6(1):e00381. doi:10.1002/prp2.381.
   PubMed Web of Science ®Google Scholar
• Bhardwaj M, Bhardwaj NJ, Cueto K, Killeen TC. Hydralazine-induced liver injury: a review and discussion. BMJ Case Rep. 2021;14(8):e243278. doi:10.1136/bcr-2021-243278.
   PubMedGoogle Scholar
• Luk T, Edwards BD, Bates D, Evernden C, Edwards J. Nitrofurantoin-induced liver failure: a fatal yet forgotten complication. Can Fam Physician. 2021;67(5):342–4. doi:10.46747/cfp.6705342.
   PubMed Web of Science ®Google Scholar
• Popp T, Balszuweit F, Schmidt A, Eyer F, Thiermann H, Steinritz D. Assessment of α-amanitin toxicity and effects of silibinin and penicillin in different in vitro models. Toxicol Vitro. 2020;67:104921. doi:10.1016/j.tiv.2020.104921.
   PubMed Web of Science ®Google Scholar
• Zou W, Devi SS, Sparkenbaugh E, Younis HS, Roth RA, Ganey PE. Hepatotoxic interaction of sulindac with lipopolysaccharide: role of the hemostatic system. Toxicol Sci. 2009;108(1):184–93. doi:10.1093/toxsci/kfn259.
   PubMed Web of Science ®Google Scholar
• Ekere OU, Ogunka-Nnoka CU, Monago-Ighorodje CC. Hepatotoxicity and nephrotoxicity studies of ethanol extracts of Annona muricata leaves and Fagara zanthoxyloide roots on zidovudine-induced Wistar rats. JALSI. 2019;4(1):1–53. doi:10.9734/jalsi/2019/v21i330106.
   Google Scholar
• Thompson M, Jaiswal Y, Wang I, Williams L. Hepatotoxicity: treatment, causes, and applications of medicinal plants as therapeutic agents. J Phytopharmacol. 2017;6(3):186–93. doi:10.31254/phyto.2017.6308.
   Google Scholar
• Joshi BC, Prakash A, Kalia AN. Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl4 challenged rats. Toxicol Rep. 2015;2:1101–10. doi:10.1016/j.toxrep.2015.07.020.
   PubMedGoogle Scholar