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image of Astragalus Injection Modulates the Pharmacokinetics of Doxorubicin and CYP450 Enzymes

Abstract

Background

Doxorubicin (DOX) is a widely used anthracycline antibiotic for the treatment of breast cancer, liver cancer, lymphoma, and other malignant tumors. However, its clinical application is limited by the side effects and drug resistance. Astragalus injection has been combined with DOX in the treatment of cancer, which improves the curative effect and reduces drug resistance. This study investigated the interaction between DOX and Astragalus injection and elucidated the potential mechanism.

Methods

The pharmacokinetics of DOX injection (7 mg/kg, intraperitoneal injection) with or without Astragalus injection (4.25 mL/kg/day for 14 days, intraperitoneal injection) were investigated in plasma from male Sprague-Dawley rats ( = 6) by UPLC-MS/MS. The group without the Astragalus injection was set as the control group. Additionally, the effects of Astragalus injection on CYP450 enzyme activities were assessed using a rat liver microsome incubation system with cocktail probe drugs.

Results

Astragalus injection significantly increased the C (2090.01 ± 99.60 5262.77 ± 111.15 ng/mL) and AUC (1190.23 ± 104.43 . 3777.27 ± 130.55 μg/L × h) and prolonged the t (0.09 ± 0.02 . 0.14 ± 0.04 h) of DOX. Astragalus injection significantly inhibited the activity of CYP1A2, CYP2C9, CYP2E1, and CYP3A4, and enhanced the activity of CYP2D1 with a metabolic elimination rate of 30.11 ± 2.67% 19.66 ± 3.41%, 35.95 ± 2.57% 23.26 ± 3.57%, 13.43 ± 2.56% 9.06 ± 2.51%, 47.90 ± 6.30% 25.87 ± 2.55%, 17.62 ± 1.49% 24.12 ± 2.91%, respectively ( < 0.05).

Conclusion

The co-administration of DOX and Astragalus injection alters the systemic exposure of DOX by affecting the metabolism of DOX and the activity of CYP450 enzymes. These findings highlight the importance of drug-drug interactions when combining Astragalus injection with DOX and provide a basis for optimizing combination therapies to address DOX resistance and toxicity.

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2025-06-04
2025-08-16
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References

  1. Shafei A. El-Bakly W. Sobhy A. Wagdy O. Reda A. Aboelenin O. Marzouk A. Habak E.K. Mostafa R. Ali M.A. Ellithy M. A review on the efficacy and toxicity of different doxorubicin nanoparticles for targeted therapy in metastatic breast cancer. Biomed. Pharmacother. 2017 95 1209 1218 10.1016/j.biopha.2017.09.059 28931213
    [Google Scholar]
  2. Yu J. Wang C. Kong Q. Wu X. Lu J.J. Chen X. Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products. Phytomedicine 2018 40 125 139 10.1016/j.phymed.2018.01.009 29496165
    [Google Scholar]
  3. Wang N. Wei R.B. Li Q.P. Yang X. Chen X.M. Protective effects of astragaloside in rats with adriamycin nephropathy and underlying mechanism. Chin. J. Nat. Med. 2016 14 4 270 277 10.1016/S1875‑5364(16)30027‑9 27114314
    [Google Scholar]
  4. Pugazhendhi A. Edison T.N.J.I. Velmurugan B.K. Jacob J.A. Karuppusamy I. Toxicity of Doxorubicin (Dox) to different experimental organ systems. Life Sci. 2018 200 26 30 10.1016/j.lfs.2018.03.023 29534993
    [Google Scholar]
  5. Chang H.L. Kuo Y.H. Wu L.H. Chang C.M. Cheng K.J. Tyan Y.C. Lee C.H. The extracts of Astragalus membranaceus overcome tumor immune tolerance by inhibition of tumor programmed cell death protein ligand-1 expression. Int. J. Med. Sci. 2020 17 7 939 945 10.7150/ijms.42978 32308547
    [Google Scholar]
  6. Fu J. Wang Z. Huang L. Zheng S. Wang D. Chen S. Zhang H. Yang S. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother. Res. 2014 28 9 1275 1283 10.1002/ptr.5188 25087616
    [Google Scholar]
  7. D’Avino D. Cerqua I. Ullah H. Spinelli M. Matteo D.R. Granato E. Capasso R. Maruccio L. Ialenti A. Daglia M. Roviezzo F. Rossi A. Beneficial Effects of Astragalus membranaceus (Fisch.) Bunge Extract in Controlling Inflammatory Response and Preventing Asthma Features. Int. J. Mol. Sci. 2023 24 13 10954 10.3390/ijms241310954 37446131
    [Google Scholar]
  8. Zhang X. Liang T. Yang W. Zhang L. Wu S. Yan C. Li Q. Astragalus membranaceus injection suppresses production of interleukin-6 by activating autophagy through the AMPK-mTOR pathway in lipopolysaccharide-stimulated macrophages. Oxid. Med. Cell. Longev. 2020 2020 1364147 32724488
    [Google Scholar]
  9. Guo J. Zhao N. Jin P. Yin Y. Effect of Astragalus injection on inflammatory mediators in patients with viral myocarditis: A systematic review and meta-analysis. Phytomedicine 2022 107 154436 10.1016/j.phymed.2022.154436 36115170
    [Google Scholar]
  10. Khan H.M. Raza S.M. Anjum A.A. Ali M.A. Antiviral, embryo toxic and cytotoxic activities of Astragalus membranaceus root extracts. Pak. J. Pharm. Sci. 2019 32 1 137 142 30772802
    [Google Scholar]
  11. Li S. Sun Y. Huang J. Wang B. Gong Y. Fang Y. Liu Y. Wang S. Guo Y. Wang H. Xu Z. Guo Y. Anti-tumor effects and mechanisms of Astragalus membranaceus (AM) and its specific immunopotentiation: Status and prospect. J. Ethnopharmacol. 2020 258 112797 10.1016/j.jep.2020.112797 32243990
    [Google Scholar]
  12. Cho W.C.S. Leung K.N. In vitro and in vivo anti-tumor effects of Astragalus membranaceus. Cancer Lett. 2007 252 1 43 54 10.1016/j.canlet.2006.12.001 17223259
    [Google Scholar]
  13. Sheik A. Kim K. Varaprasad G.L. Lee H. Kim S. Kim E. Shin J.Y. Oh S.Y. Huh Y.S. The anti-cancerous activity of adaptogenic herb Astragalus membranaceus. Phytomedicine 2021 91 153698 10.1016/j.phymed.2021.153698 34479785
    [Google Scholar]
  14. Fu S. Zhang J. Menniti-Ippolito F. Gao X. Galeotti F. Massari M. Hu L. Zhang B. Ferrelli R. Fauci A. Huangqi injection (a traditional Chinese patent medicine) for chronic heart failure: A systematic review. PLoS One 2011 6 5 e19604 10.1371/journal.pone.0019604
    [Google Scholar]
  15. Cao A. He H. Wang Q. Li L. An Y. Zhou X. Evidence of Astragalus injection combined platinum-based chemotherapy in advanced nonsmall cell lung cancer patients. Medicine 2019 98 11 e14798 10.1097/MD.0000000000014798 30882655
    [Google Scholar]
  16. McCulloch M. See C. Shu X. Broffman M. Kramer A. Fan W. Gao J. Lieb W. Shieh K. Colford J.M. Jr Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: Meta-analysis of randomized trials. J. Clin. Oncol. 2006 24 3 419 430 10.1200/JCO.2005.03.6392 16421421
    [Google Scholar]
  17. Sun S. Liu L. Song H. Li H. Pharmacokinetic study on the co-administration of abemaciclib and astragaloside IV in rats. Pharm. Biol. 2022 60 1 1944 1948 10.1080/13880209.2022.2125539 36226863
    [Google Scholar]
  18. Li Y.J. Lei Y.H. Yao N. Wang C.R. Hu N. Ye W.C. Zhang D.M. Chen Z.S. Autophagy and multidrug resistance in cancer. Chin. J. Cancer 2017 36 1 52 10.1186/s40880‑017‑0219‑2 28646911
    [Google Scholar]
  19. Xie T. Li Y. Li S.L. Luo H.F. Astragaloside IV enhances cisplatin chemosensitivity in human colorectal cancer via regulating NOTCH3. Oncol. Res. 2016 24 6 447 453 10.3727/096504016X14685034103590 28281965
    [Google Scholar]
  20. Qu X. Gao H. Zhai J. Sun J. Tao L. Zhang Y. Song Y. Hu T. Astragaloside IV enhances cisplatin chemosensitivity in hepatocellular carcinoma by suppressing MRP2. Eur. J. Pharm. Sci. 2020 148 105325 10.1016/j.ejps.2020.105325 32259679
    [Google Scholar]
  21. Liang Y. Chen B. Liang D. Quan X. Gu R. Meng Z. Gan H. Wu Z. Sun Y. Liu S. Dou G. Pharmacological effects of astragaloside IV: A review. Molecules 2023 28 16 6118 10.3390/molecules28166118 37630371
    [Google Scholar]
  22. Zheng Y. Dai Y. Liu W. Wang N. Cai Y. Wang S. Zhang F. Liu P. Chen Q. Wang Z. Astragaloside IV enhances taxol chemosensitivity of breast cancer via caveolin‐1‐targeting oxidant damage. J. Cell. Physiol. 2019 234 4 4277 4290 10.1002/jcp.27196 30146689
    [Google Scholar]
  23. Zhou R. Guo T. Li J. Research progress on the antitumor effects of astragaloside IV. Eur. J. Pharmacol. 2023 938 175449 10.1016/j.ejphar.2022.175449 36473596
    [Google Scholar]
  24. Xiu W. Zhang Y. Tang D. Lee S.H. Zeng R. Ye T. Li H. Lu Y. Qin C. Yang Y. Yan X. Wang X. Hu X. Chu M. Sun Z. Xu W. Inhibition of EREG/ErbB/ERK by Astragaloside IV reversed taxol-resistance of non-small cell lung cancer through attenuation of stemness via TGFβ and Hedgehog signal pathway. Cell Oncol. 2024 47 6 2201 2215 10.1007/s13402‑024‑00999‑7 39373858
    [Google Scholar]
  25. Zhang Y. Zhou Q. Ding X. Wang H. Tan G. HILIC-MS-based metabolomics reveal that Astragalus polysaccharide alleviates doxorubicin-induced cardiomyopathy by regulating sphingolipid and glycerophospholipid homeostasis. J. Pharm. Biomed. Anal. 2021 203 114177 10.1016/j.jpba.2021.114177 34198197
    [Google Scholar]
  26. Wang D. Cui Q. Yang Y.J. Liu A.Q. Zhang G. Yu J.C. Application of dendritic cells in tumor immunotherapy and progress in the mechanism of anti-tumor effect of Astragalus polysaccharide (APS) modulating dendritic cells: A review. Biomed. Pharmacother. 2022 155 113541 10.1016/j.biopha.2022.113541 36127221
    [Google Scholar]
  27. Li W. Hu X. Wang S. Jiao Z. Sun T. Liu T. Song K. Characterization and anti-tumor bioactivity of astragalus polysaccharides by immunomodulation. Int. J. Biol. Macromol. 2020 145 985 997 10.1016/j.ijbiomac.2019.09.189 31669273
    [Google Scholar]
  28. Li Q. Zhang C. Xu G. Shang X. Nan X. Li Y. Liu J. Hong Y. Wang Q. Peng G. Astragalus polysaccharide ameliorates CD8+ T cell dysfunction through STAT3/Gal-3/LAG3 pathway in inflammation‐induced colorectal cancer. Biomed. Pharmacother. 2024 171 116172 10.1016/j.biopha.2024.116172 38278025
    [Google Scholar]
  29. Lin J. Fang L. Li H. Li Z. Lyu L. Wang H. Xiao J. Astragaloside IV alleviates doxorubicin induced cardiomyopathy by inhibiting NADPH oxidase derived oxidative stress. Eur. J. Pharmacol. 2019 859 172490 10.1016/j.ejphar.2019.172490 31229536
    [Google Scholar]
  30. Tang Q. Zhang M. Hong Z. Chen Y. Wang P. Wang J. Wang Z. Fang R. Jin M. Effects of astragalus injection on different stages of early hepatocarcinogenesis in a two-stage hepatocarcinogenesis model using rats. J. Toxicol. Pathol. 2019 32 3 155 164 10.1293/tox.2019‑0006 31402807
    [Google Scholar]
  31. Zeng R. Li H. Jia L. Lee S.H. Jiang R. Zhang Y. Hu X. Ye T. Wang X. Yan X. Lu Y. Sun Z. Xu J. Xu W. Association of CYP24A1 with survival and drug resistance in clinical cancer patients: A meta-analysis. BMC Cancer 2022 22 1 1317 10.1186/s12885‑022‑10369‑x 36527000
    [Google Scholar]
  32. Mokhosoev I.M. Astakhov D.V. Terentiev A.A. Moldogazieva N.T. Human Cytochrome P450 Cancer-Related Metabolic Activities and Gene Polymorphisms: A Review. Cells 2024 13 23 1958 10.3390/cells13231958 39682707
    [Google Scholar]
  33. Szeląg-Pieniek S. Oswald S. Post M. Łapczuk-Romańska J. Droździk M. Kurzawski M. Hepatic drug-metabolizing enzymes and drug transporters in Wilson’s disease patients with liver failure. Pharmacol. Rep. 2021 73 5 1427 1438 10.1007/s43440‑021‑00290‑8 34117631
    [Google Scholar]
  34. Almazroo O.A. Miah M.K. Venkataramanan R. Drug metabolism in the liver. Clin. Liver Dis. 2017 21 1 1 20 10.1016/j.cld.2016.08.001 27842765
    [Google Scholar]
  35. Amacher D.E. The primary role of hepatic metabolism in idiosyncratic drug-induced liver injury. Expert Opin. Drug Metab. Toxicol. 2012 8 3 335 347 10.1517/17425255.2012.658041 22288564
    [Google Scholar]
  36. Kulsharova G. Kurmangaliyeva A. Liver microphysiological platforms for drug metabolism applications. Cell Prolif. 2021 54 9 e13099 10.1111/cpr.13099 34291515
    [Google Scholar]
  37. Meng Q. Cheng Y. Zhou C. Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp. Pharm. Biol. 2021 59 1 1549 1553 10.1080/13880209.2021.1999988 34757861
    [Google Scholar]
  38. Lam P.Y. Kutchukian P. Anand R. Imbriglio J. Andrews C. Padilla H. Vohra A. Lane S. Parker D.L. Jr Taracido C.I. Johns D.G. Beerens M. MacRae C.A. Caldwell J.P. Sorota S. Asnani A. Peterson R.T. Cyp1 inhibition prevents doxorubicin‐induced cardiomyopathy in a zebrafish heart‐failure model. ChemBioChem 2020 21 13 1905 1910 10.1002/cbic.201900741 32003101
    [Google Scholar]
  39. Dhulkifle H. Therachiyil L. Hasan M.H. Sayed T.S. Younis S.M. Korashy H.M. Yalcin H.C. Maayah Z.H. Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity. Mol. Biol. Rep. 2024 51 1 859 10.1007/s11033‑024‑09803‑z 39066934
    [Google Scholar]
  40. Sun B. Yang Y. He M. Jin Y. Cao X. Du X. Yang R. Hepatoprotective role of berberine on doxorubicin induced hepatotoxicity - involvement of cyp. Curr. Drug Metab. 2020 21 7 541 547 10.2174/1389200221666200620203648 32586251
    [Google Scholar]
  41. Kaur G. Gupta S.K. Singh P. Ali V. Kumar V. Verma M. Drug-metabolizing enzymes: Role in drug resistance in cancer. Clin. Transl. Oncol. 2020 22 10 1667 1680 10.1007/s12094‑020‑02325‑7 32170639
    [Google Scholar]
  42. Asnani A. Zheng B. Liu Y. Wang Y. Chen H.H. Vohra A. Chi A. Cornella-Taracido I. Wang H. Johns D.G. Sosnovik D.E. Peterson R.T. Highly potent visnagin derivatives inhibit Cyp1 and prevent doxorubicin cardiotoxicity. JCI Insight 2018 3 1 e96753 10.1172/jci.insight.96753 29321375
    [Google Scholar]
  43. Arnold W.R. Das A. An emerging pathway of doxorubicin cardiotoxicity mediated through CYP2J2. Biochemistry 2018 57 16 2294 2296 10.1021/acs.biochem.8b00337 29629756
    [Google Scholar]
  44. Santos D.K.F. Materón E.M. Oliveira O.N. Jr Influence of cytochrome P450 3A4 and membrane lipid composition on doxorubicin activity. Colloids Surf. B Biointerfaces 2022 220 112886 10.1016/j.colsurfb.2022.112886 36183636
    [Google Scholar]
  45. Grant M.K.O. Abdelgawad I.Y. Lewis C.A. Zordoky B.N. Sexual dimorphism in doxorubicin-induced systemic inflammation: Implications for hepatic cytochrome p450 regulation. Int. J. Mol. Sci. 2020 21 4 1279 10.3390/ijms21041279 32074957
    [Google Scholar]
  46. Kabe Y. Nakane T. Koike I. Yamamoto T. Sugiura Y. Harada E. Sugase K. Shimamura T. Ohmura M. Muraoka K. Yamamoto A. Uchida T. Iwata S. Yamaguchi Y. Krayukhina E. Noda M. Handa H. Ishimori K. Uchiyama S. Kobayashi T. Suematsu M. Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance. Nat. Commun. 2016 7 1 11030 10.1038/ncomms11030 26988023
    [Google Scholar]
  47. Rosic G. Cancer signaling, cell/gene therapy, diagnosis and role of nanobiomaterials. 2024 9 Special Issue 11 34 10.62476/abes9s11
    [Google Scholar]
  48. Khalilov R. Bakishzade A. Nasibova A. Future prospects of biomaterials in nanomedicine. Adv. Biol. Earth Sci. 2023 8 Special Issu 5 10 10.62476/abes.9s5
    [Google Scholar]
  49. Huseynov E. Khalilov R. Mohamed A.J. Novel nanomaterials for hepatobiliary diseases treatment and future perspectives. Adv. Biol. Earth Sci. 2024 9 Special Issue 81 91 10.62476/abes9s81
    [Google Scholar]
  50. Rodrigo L. Gil F. Hernandez A.F. Lopez O. Pla A. Identification of paraoxonase 3 in rat liver microsomes: Purification and biochemical properties. Biochem. J. 2003 376 1 261 268 10.1042/bj20030732 12946270
    [Google Scholar]
  51. Li L. Shi H. Hua X. Wang M. Wang H. Intrinsic clearance and metabolism pathway of fosthiazate in rat and cock liver microsomes: From chiral assessment view. J. Agric. Food Chem. 2021 69 43 12654 12660 10.1021/acs.jafc.1c05217 34695356
    [Google Scholar]
  52. Price R.J. Scott M.P. Cantrill C. Higgins L.G. Moreau M. Yoon M. Clewell H.J. Creek M.R. Osimitz T.G. Houston J.B. Lake B.G. Kinetics of metabolism of deltamethrin and cis - and trans -permethrin in vitro. Studies using rat and human liver microsomes, isolated rat hepatocytes and rat liver cytosol. Xenobiotica 2021 51 1 40 50 10.1080/00498254.2020.1807075 32757971
    [Google Scholar]
  53. Kielkopf C.L. Bauer W. Urbatsch I.L. Bradford assay for determining protein concentration. Cold Spring Harb. Protoc. 2020 2020 4 pdb.prot102269 10.1101/pdb.prot102269 32238597
    [Google Scholar]
  54. Kielkopf C.L. Bauer W. Urbatsch I.L. Methods for measuring the concentrations of proteins. Cold Spring Harb. Protoc. 2020 2020 4 pdb.top102277 10.1101/pdb.top102277 32238598
    [Google Scholar]
  55. Wu S.A. Shen C. Wei X. Zhang X. Wang S. Chen X. Torres M. Lu Y. Lin L.L. Wang H.H. Hunter A.H. Fang D. Sun S. Ivanova M.I. Lin Y. Qi L. The mechanisms to dispose of misfolded proteins in the endoplasmic reticulum of adipocytes. Nat. Commun. 2023 14 1 3132 10.1038/s41467‑023‑38690‑4 37253728
    [Google Scholar]
  56. He Z.H. Shao L.Q. Xuan L.Y. Wang C.G. Wei C.X. Wang Y. Zhao M. [Effect of Astragalus injection on cardiomyocyte apoptosis, endoplasmic reticulum stress and expression of connexin in cardiomyopathy rats induced by adriamycin]. Chung Kuo Ying Yung Sheng Li Hsueh Tsa Chih 2018 34 2 159 163 29926682
    [Google Scholar]
  57. Clar J. Gri B. Calderaro J. Birling M.C. Hérault Y. Smit G.P.A. Mithieux G. Rajas F. Targeted deletion of kidney glucose-6 phosphatase leads to nephropathy. Kidney Int. 2014 86 4 747 756 10.1038/ki.2014.102 24717294
    [Google Scholar]
  58. Luo Z. Liu Y. Zhao Z. Yan X. Wang D. Liu Q. Effects of Astragalus injection and Salvia Miltiorrhiza injection on serum inflammatory markers in patients with stable coronary heart disease: A randomized controlled trial protocol. Trials 2020 21 1 267 10.1186/s13063‑020‑4109‑6 32178701
    [Google Scholar]
  59. Liu K. Wan G. Jiang R. Zou L. Wan D. Zhu H. Feng S. Astragalus injection ameliorates lipopolysaccharide-induced cognitive decline via relieving acute neuroinflammation and BBB damage and upregulating the BDNF-CREB pathway in mice. Pharm. Biol. 2022 60 1 825 839 10.1080/13880209.2022.2062005 35587259
    [Google Scholar]
  60. Sun Y. He M. Sun Y. Wei J. 4-O-galloylalbiflorin inhibits the activity of CYP3A, 2C9, and 2D in human liver microsomes. Xenobiotica 2021 51 8 871 876 10.1080/00498254.2021.1936688 34082641
    [Google Scholar]
  61. Schneider D. Bier D. Bauer A. Neumaier B. Holschbach M. Influence of incubation conditions on microsomal metabolism of xanthine-derived A1 adenosine receptor ligands. J. Pharmacol. Toxicol. Methods 2019 95 16 26 10.1016/j.vascn.2018.11.005 30476620
    [Google Scholar]
  62. Zhu L.J. Sun S.S. Hu Y.X. Liu Y.F. Metabolism studies of paeoniflorin in rat liver microsomes by ultra-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). R. Soc. Open Sci. 2018 5 10 180759 10.1098/rsos.180759 30473826
    [Google Scholar]
  63. Hakkola J. Hukkanen J. Turpeinen M. Pelkonen O. Inhibition and induction of CYP enzymes in humans: An update. Arch. Toxicol. 2020 94 11 3671 3722 10.1007/s00204‑020‑02936‑7 33111191
    [Google Scholar]
  64. Saiz-Rodríguez M. Ochoa D. Belmonte C. Román M. Vieira de Lara D. Zubiaur P. Koller D. Mejía G. Abad-Santos F. Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics. J. Psychopharmacol. 2019 33 4 522 531 10.1177/0269881119827959 30789308
    [Google Scholar]
  65. Yu J. Xia X. Dong Y. Gong Z. Li G. Chen G.G. Lai P.B.S. CYP1A2 suppresses hepatocellular carcinoma through antagonizing HGF/MET signaling. Theranostics 2021 11 5 2123 2136 10.7150/thno.49368 33500715
    [Google Scholar]
  66. Holbrook A.M. Pereira J.A. Labiris R. McDonald H. Douketis J.D. Crowther M. Wells P.S. Systematic overview of warfarin and its drug and food interactions. Arch. Intern. Med. 2005 165 10 1095 1106 10.1001/archinte.165.10.1095 15911722
    [Google Scholar]
  67. Boccia S. Miele L. Panic N. Turati F. Arzani D. Cefalo C. Amore R. Bulajic M. Pompili M. Rapaccini G. Gasbarrini A. Vecchia L.C. Grieco A. The effect of CYP, GST, and SULT polymorphisms and their interaction with smoking on the risk of hepatocellular carcinoma. BioMed Res. Int. 2015 2015 1 7 10.1155/2015/179867 25654087
    [Google Scholar]
  68. Gao J. Wang Z. Wang G.J. Zhang H.X. Gao N. Wang J. Wang C.E. Chang Z. Fang Y. Zhang Y.F. Zhou J. Jin H. Qiao H.L. Higher CYP2E1 activity correlates with hepatocarcinogenesis induced by diethylnitrosamine. J. Pharmacol. Exp. Ther. 2018 365 2 398 407 10.1124/jpet.117.245555 29467309
    [Google Scholar]
  69. Yin X. Xiong W. Wang Y. Tang W. Xi W. Qian S. Guo Y. Association of CYP2E1 gene polymorphisms with bladder cancer risk. Medicine 2018 97 39 e11910 10.1097/MD.0000000000011910 30278485
    [Google Scholar]
  70. Guengerich F.P. Cytochrome P450 2E1 and its roles in disease. Chem. Biol. Interact. 2020 322 109056 10.1016/j.cbi.2020.109056 32198084
    [Google Scholar]
  71. Lu Y. Wang Y. He Y. Pan J. Jin Y. Zheng L. Huang Y. Li Y. Liu W. Aidi injection altered the activity of CYP2D4, CYP1A2, CYP2C19, CYP3A2, CYP2E1 and CYP2C11 in normal and diethylnitrosamine-induced hepatocellular carcinoma in rats. J. Ethnopharmacol. 2022 286 114930 10.1016/j.jep.2021.114930 34952190
    [Google Scholar]
  72. Kiani Y.S. Ranaghan K.E. Jabeen I. Mulholland A.J. Molecular dynamics simulation framework to probe the binding hypothesis of CYP3A4 inhibitors. Int. j. Mol. Sci. 2019 20 18 4468 10.3390/ijms20184468 31510073
    [Google Scholar]
  73. Hu Y. Quan Z. Li D. Wang C. Sun Z. Inhibition of CYP3A4 enhances aloe-emodin induced hepatocyte injury. Toxicol. In Vitro 2022 79 105276 10.1016/j.tiv.2021.105276 34875353
    [Google Scholar]
  74. liu Q. Ou-Yang Q.G. Lin Q.M. Lu X.R. Ma Y.Q. Li Y.H. Xu R.A. Lin D. Hu G.X. Cai J.P. Effects of 27 CYP3A4 protein variants on saxagliptin metabolism in vitro. Fundam. Clin. Pharmacol. 2022 36 1 150 159 10.1111/fcp.12693 33961299
    [Google Scholar]
  75. Zanger U.M. Schwab M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther. 2013 138 1 103 141 10.1016/j.pharmthera.2012.12.007 23333322
    [Google Scholar]
  76. Mo S.L. Liu Y.H. Duan W. Wei M. Kanwar J. Zhou S.F. Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Curr. Drug Metab. 2009 10 7 730 753 10.2174/138920009789895534 19702527
    [Google Scholar]
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  • Article Type:
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Keywords: Drug-drug interaction ; drug resistance ; Astragali radix ; metabolism ; CYP1A2 ; CYP3A4
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