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Effects of Korean traditional herbal formula for common cold on the activities of human CYP450 isozymes

  • Jin, Seong Eun (Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine) ;
  • Ha, Hyekyung (Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine) ;
  • Jeong, Soo-Jin (Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine) ;
  • Shin, Hyeun-Kyoo (Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine)
  • Received : 2014.04.02
  • Accepted : 2014.06.23
  • Published : 2014.06.30

Abstract

Objectives: Most drug interactions are attributed to the inhibition or induction of the activity of cytochrome P450s (CYP450). Although the regulation of CYP450s by drugs has been widely reported, there have been few studies on influence of traditional herbal formulas on the drug-metabolizing enzymes. Because herbal formulas have been used traditionally to treat various diseases and because herb-drug interactions are crucial factors determining therapeutic efficacies, a systematic evaluation of the effects of herbal formulas is important. Methods: The effects of Galgeun-tang (GGT, gegen tang), Gumiganghwal-tang (GMGHT, jiuweiqianghuo tang), Insampaedok-san (ISPDS, renshenbaidu powder), Samsoeum (SSE, shensu drink), Socheongryong-tang (SCRT, xiaoqinglong-tang) and Sosiho-tang (SSHT, xiaochaihu tang) that are traditional herbal formulas used to treat common cold, on drug-metabolizing enzymes were evaluated through an in vitro CYP3A4, CYP2D6, CYP2C19 and CYP2E1 inhibition assay to assess its interaction potential with synthetic drugs. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results: These six herbal formulas inhibited the activities of CYP3A4, 2C19, 2D6 and 2E1, in a concentration-dependent manner. Among the six herbal formulas, GGT critically inhibited CYP2C19, CYP2D6 and CYP2E1. GMGHT also inhibited CYP2D6 and CYP2E1 to a greater extent than the other CYP450 isozymes. Additionally, SSE and SSHT may change the effects of medicines that depend primarily on the CYP2C19 and CYP2E1 pathways. On the other hand, ISPDS and SCRT were not inhibited CYP3A4, CYP2C19, CYP2D6 and CYP2E1-mediated metabolism. Conclusions: These findings provide useful information regarding the safety and effectiveness of herbal formulas.

Keywords

References

  1. Watkins PB. Drug metabolism by cytochromes P450 in the liver and small bowel. Gastroenterol Clin North Am. 1992;21(3):51126.
  2. Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol. 2007;100(1):2330.
  3. Liu R, Qin M, Hang P, Liu Y, Zhang Z, Liu G. Effects of Panax notoginseng saponins on the activities of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 in rats in vivo. Phytotherapy Res. 2011;26(8):11138.
  4. Seo CS, Huang DS, Lee JK, Ha HK, Chun JM, Um YR, et al. Concentration of heavy metals, residual pesticides and sulfur dioxide of before/after a decoction. Kor J Herbology. 2008;23(4):518.
  5. Kim JH, Shin HK. Analysis of biological experiment on Socheongryong-tang (Xiaoqinglongang). J Korean Oriental Med. 2012;33(3):5473.
  6. Yang TK, Kim YB, Chae BY. An experimental study on the anti-allergic effects, anti-inflammatory action, anti-pyretic action and analgesic action of Galgeun-tang, Gamigalgeun-tang and Geomahwanggalgeun-ang. J Korean Oriental Med Ophthalmol tolaryngol Dermatol. 2002; 15(1):7695.
  7. Moon YH, Go JJ, Park JY. The antiinflammatory and analgesic activities of Gumiganghwaltang. Korean J Pharmacognosy. 1999;30(1):1824.
  8. Shim JY, Kim BW. A study of effects of Insampaedok-san and Kammiinsampaedok san on the analgesia, antipyresis and thioacetamide induced liver damage in rats and mice. Kyung-Hee Univ Orient Med J. 1984;7(1): 32334.
  9. Choi SB, Rhee HK. A study of effects of Samsoeum on the analgesia, antipyresis and $O_{3}$ poisoned lung in rats and mice. Kyung-Hee Univ Orient Med J. 1985;8:13948.
  10. Yamahara J, Yamada T, Kimura H, Sawada T, Fujimura H. Biologically active principles of crude drugs. II. Anti-allergic principles in "Shoseiryu-To" anti-inflammatory properties of paeoniflorin and its derivatives. J Pharmacobiodyn. 1982;5(11):9219.
  11. Woo HJ, Kim DH, Kim BW. A experimental and clinical study on effects of Soshiho-tang. Kyung-Hee Univ Orient Med J. 1990;6(1): 97107.
  12. Lee JA, Ha H, Jung DY, Lee H, Lee JK, Huang DS, et al. Comparative study of 25 herbal formulas on anti-inflammatory effect. J Orient Gynecol. 2010;23(3):10111.
  13. Shin JM, Kim YO, Baek SH. Free radical scavenging activity and kinetic behavior of the Galgeuntang water extract. Kyung-Hee Univ Orient Med J. 2008;8(1):3238.
  14. Wu MS, Yen HR, Chang CW, Peng TY, Heish CF, Chen CJ, et al. Mechanism of action of the suppression of influenza virus replication by Ko-Ken Tang through inhibition of the phosphatidylinositol 3-kinase/Akt signaling pathway and viral RNP nuclear export. J Ethnopharmacol. 2011;134(3):61423.
  15. Jeong HJ, Hong MC, Shin MK, Bae HS. Sochungyong-tang, tradititional Korean medicine, suppresses Th2 lineage development. Korean J Orient Physiol Pathol. 2005;19(2): 3808.
  16. Kim JH, Shin HK. Analysis of biological experiment on Socheongryong-tang. J Korean Orient Med. 2012,33(3):5473.
  17. Lee JW, Jung HJ, Jung SG, Lee HG. The effects of Socheoryong-tang on lymphocytes in BALF of rat. Orient Pharm Exp Med. 2001;17(2): 24253.
  18. Seo CS, Lim JH, Shin HK. Simultaneous determination of albiflorin, cinnamaldehyde, cinnamic acid, daidzin, glycyrrhizin, liquiritin, paeoniflorin and puerarin in Galgeun-tang by HPLC-PDA. J Korean Orient Med. 2010;31(6): 815.
  19. Shin IS, Seo CS, Lee MY, Ha HK, Huh JI, Shin HK. In vitro and in vivo evaluation of the genotoxicity of Gumiganghwal-tang, a traditional herbal prescription. J Ethnopharmacol. 2012; 141(1):3506.
  20. Seo CS, Kim JH, Shin HK. Simultaneous determination of six major constituents of the herbal formula Insampaedok-san using HPLC-PDA. ISRN Anal Chem. 2012; Article ID 609587.
  21. Seo CS, Kim JH, Huang DS, Shin HK. Simultaneous determination of seven compounds in Samsoeum by HPLC-PDA. Korean J Orient Med Prescription. 2010;18(1):95103.
  22. Kim JH, Jeon WY, Lee MY, Seo CS, Lim HS, Shin HK. Inhibitory activity of Socheongryongtang and its constituent components against the production of RANTES, eotaxin, eotaxin-3, and MMP-9 from BEAS2B-cells. Spandidos Publ. 2014 (in press).
  23. Shin IS, Lee MY, Kim Y, Seo CS, Kim JH, Shin HK. Subacute toxicity and stability of Soshihotang, a traditional herbal formula, in Sprague- Dawley rats. BMC Complement & Altern Med. 2012;12:26675.
  24. Goshman L, Roller K. Clinically significant cytochrome P450 drug interactions. J Pharm Soc Wis. 1999;3:2338.
  25. Lee HW, Kim DW, Phapale PB, Lim MS, Park J, Seo JJ, et al. In vitro inhibitory effects of Wen-pi-tang-Hab-Wu- ling-san on human cytochrome P450 isoforms. J Clin Pharm Ther. 2011;36(4):496503.
  26. Xu C, Li CY, Kong AN. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res. 2005;28(3):24968.
  27. Saxena A, Tripathi KP, Roy S, Khan F, Sharma A. Pharmacovigilance: effects of herbal components on human drugs interactions involving cytochrome P450. Bioinformation. 2008;3(5):198204.
  28. Foti RS, Rock DA, Wienkers LC, Wahlstrom JL. Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metabolism Disposition. 2010;38(6):9817.
  29. Guerra MC, Speroni E, Broccoli M, Cangini M, Pasini P, Minghett A, et al. Comparison between chinese medical herb Pueraria lobata crude extract and its main isoflavone puerarin antioxidant properties and effects on rat liver CYP-catalysed drug metabolism. Life Sci. 2000;67(24):29973006.
  30. Wu W, Liu L, Han F, Chen Y. Effect of pseudoephedrine and ephedrine on the activities of cytochrome P450 enzymes in rat liver microsomes. China J Trad Med Pharm. 2011;08.
  31. Wang Y, Ye X, Ma Z, Liang Q, Lu B, Tan H, et al. Induction of cytochrome P450 1A1 expression by ginsenoside Rg1 and Rb1 in HepG2 cells. European J Pharmacol. 2008; 601(13):738.
  32. Takahashi K, Uejima E, Morisaki T, Takahashi K, Kurokawa N, Azuma J. In vitro inhibitory effects of Kampo medicines on metabolic reactions catalyzed by human liver microsomes. J Clin Pharm Ther. 2003;28(4):31927.
  33. Park JH, Park JY, Ju YS. Inhibitory effects of licorice ethanol extracts and glycyrrhizin on Cytochrome P450 drug-metabolizing enzymes in human liver microsomes. Korean J Orient Prev Med Soc. 2003;7(2):6574.
  34. Hou YN, Zhu XY, Cheng GF. Effects of baicalin on liver microsomal cytochrome P450 system. Acta Pharmaceutica Sinica. 2000;35(12):890-2.
  35. Ueng YF, Shyu CC, Lin YL, Park SS, Liao JF, Chen CF. Effects of baicalein and wogonin on drug-metabolizing enzymes in C57BL/6J mice. Life Sci. 2000;67(18):2189-200. https://doi.org/10.1016/S0024-3205(00)00809-2
  36. Li T, Li N, Guo Q, Ji H, Zhao D, Xie S, et al. Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes. Eur J Drug Metab Pharmacokinet. 2011;36(4): 249-56. https://doi.org/10.1007/s13318-011-0050-0
  37. Ueng YF, Chang YL, Oda Y, Park SS, Liao JF, Lin MF, et al. In vitro and in vivo effects of naringin on cytochrome P450-dependent monooxygenase in mouse liver. Life Sci. 1999; 65(24):2591-602. https://doi.org/10.1016/S0024-3205(99)00528-7

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