Impacts of Kampo medicine on induction of CYP3A4 and ABCB1 in gastrointestinal cell model LS180

الموضوعات : مجله گیاهان دارویی

Kana Hashimoto ¹ , Daichi Enomoto ² , Shion Ohsawa ³ , Saki Aoki ⁴ , Kai Tanaka ⁵ , Runa Yamauchi ⁶ , Yuko Nakayama ⁷ , Kohji Takara ⁸

1 - Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan;
2 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan;
3 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan;
4 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan;
5 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan;
6 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan;
7 - Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University; Himeji, Japan;
8 - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University, Kobe, Japan;

تاريخ الإرسال : 23 الأربعاء , شعبان, 1444 تاريخ التأكيد : 04 الخميس , ذو الحجة, 1444 تاريخ الإصدار : 04 الخميس , ذو الحجة, 1444

الکلمات المفتاحية: Cyp3a4, Kampo medicine, ABCB1, LS180 cell,

ملخص المقالة :

Background & Aim: The clinical use of some Kampo medicines has increased rapidly, and opportunities to be used concomitantly with Western medicines more frequently. Although the inhibition of cytochrome P450(CYP)-mediated drug metabolism and ABCB1-mediated transport by Kampo medicine has been reported, little information is available regarding the induction of CYP enzymes or P-glycoprotein—which is encoded by the highly polymorphic ATP-binding cassette transporter B1 (ABCB1) gene—by Kampo medicine. This study aimed to evaluate the induction of CYP enzymes and ABCB1 using Kampo medicines.Experimental: Four Kampo medicines, namely Saireito, Shosaikoto, Goreisan, and Daikenchuto, were selected. The induction of CYP3A4 and ABCB1mRNA expressionwas evaluated in human-derived colon adenocarcinoma LS180 cells, which are an established model for investigating gene induction mediated by the pregnane X receptor.Results: Exposure to Saireito caused a dose-dependent increase in CYP3A4 mRNA expression. A significant increase in CYP3A4 mRNA expression was also observed with Goreisan and Daikenchuto, but not with Shosaikoto. Exposure to Saireito, Shosaikoto, and Goreisan significantly upregulated the expression of ABCB1 mRNA in a dose-dependent manner, but exposure to Daikenchuto had no such effect. These results indicate the differing induction effects of Kampo medicines and the distinct profiles of CYP3A4 and ABCB1, suggesting the upregulation of CYP3A4 or ABCB1 expression by Kampo medicines in enterocytes.Recommended applications/industries: Collectively, our results show that Kampo medicines can potentially induce the expression of CYP enzymes and ABCB1, and provide useful clinical information on the safety and efficacy of the combined use of Kampo and Western medicines.

المصادر:

Brandin, H.,Viitanen, E., Myrberg, O. and Arvidsson, A.K. 2007. Effects of herbal medicinal products and food supplements on induction of CYP1A2, CYP3A4 and MDR1 in the human colon carcinoma cell line LS180. Phytotherapy Research, 21: 239-244.
Ernst, E. 2004. Are herbal medicines effective? International Journal of Clinical Pharmacology and Therapeutics, 42: 157-159.
Fugh-Berman, A. 2000. Herb-drug interactions. Lancet, 355: 134-138.
Hyuga, S., Shiraishi, M., Hori, A., Hyuga, M. and Hanawa, T. 2012. Effects of Kampo medicines on MDR-1-mediated multidrug resistance in human hepatocellular carcinoma HuH-7/PTX cells. Biological and Pharmaceutical Bulletin, 35: 1729-1739.
Ito, K., Satoh, T., Watanabe, Y., Ikarashi, N., Asano, T., Morita, T. and Sugiyama, K. 2008. Effects of Kampo medicines on CYP and P-gp activity in vitro. Biological and Pharmaceutical Bulletin, 31: 893-896.
Iwanaga, K., Hayashi, M., Hamahata, Y., Miyazaki, M., Shibano, M., Taniguchi, M., Baba, K. and Kakemi, M. 2010. Furanocoumarin derivatives in Kampo extract medicines inhibit cytochrome P450 3A4 and P-glycoprotein. Drug Metabolism & Disposition, 38: 1286-1294.
Iwata, H., Tezuka, Y., Kadota, S., Hiratsuka, A. and Watabe, T. 2004a. Metabolism-dependent inhibition of CYP3A4 and CYP2D6 by extracts from 26 herbal medicines. Journal of Traditional Medicines, 21: 281-286.
Iwata, H., Tezuka, Y., Usia, T., Kadota, S., Hiratsuka, A. and Watabe, T. 2004b. Inhibition of human liver microsomal CYP3A4 and CYP2D6 by extracts from 78 herbal medicines. Journal of Traditional Medicines, 21:42-50.
Kitada, N., Takara, K., Minegaki, T., Itoh, C., Tsujimoto, M., Sakaeda, T. and Yokoyama, T. 2008. Factors affecting sensitivity to antitumor platinum derivatives of human colorectal tumor cell lines. Cancer Chemotherapy and Pharmacology, 62: 577-584.
Matsumoto, T.,Kaifuchi, N., Mizuhara, Y., Warabi, E. and Watanabe, J. 2018. Use of a Caco-2 permeability assay to evaluate the effects of several Kampo medicines on the drug transporter P-glycoprotein. Journal of Natural Medicines, 72: 897-904.
Minegaki, T., Takara, K., Hamaguchi, R., Tsujimoto, M. and Nishiguchi, K. 2013. Factors affecting the sensitivity of human-derived esophageal carcinoma cell lines to 5-fluorouracil and cisplatin. Oncology Letters, 5: 427-434.
Motoo, Y., Seki, T. andTsutani, K. 2011. Traditional Japanese medicine, Kampo: its history and current status. Chinese Journal of Integrative Medicine, 17: 85-87.
Nicolussi, S., Drewe, J., Butterweck, V., Meyer, Z.and Schwabedissen, H.E. 2020. Clinical relevance of St. John's wort drug interactions revisited. British Journal of Pharmacology, 177: 1212-1226.
Okada, N., Murakami, A., Urushizaki, S., Matsuda, M., Kawazoe, K. and Ishizawa, K. 2017. Extracts of immature orange (Aurantii fructus immaturus) and citrus unshiu peel (Citrius unshiu pericarpium) induce P-glycoprotein and cytochrome P450 3A4 expression via upregulation of pregnane X receptor. Frontiers in Pharmacology, 8: 84-89.
Pal, S.K. and Shukla, Y. 2003. Herbal medicine: Current status and the future. Asian Pacific Journal of Cancer Prevention, 4: 281-288.
Satoh, T., Watanabe, Y., Ikarashi, N., Ito, K. and Sugiyama, K. 2009. Effects of Kampo medicines on P-glycoprotein. Biological and Pharmaceutical Bulletin, 32: 2018-2021.
Takara, K., Horibe, S., Obata, Y., Yoshikawa, E., Ohnishi, N. and Yokoyama, T. 2005. Effects of 19 herbal extracts on the sensitivity to paclitaxel or 5-fluorouracil in HeLa cells. Biological and Pharmaceutical Bulletin, 28: 138-142.
Takara, K., Takagi, K., Tsujimoto, M., Ohnishi, N. and Yokoyama, T. 2003. Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and simultaneously down-regulates steroid xenobiotic receptor mRNA. Biochemical and Biophysical Research Communications, 306: 116-120.
Takiyama, M., Matsumoto, T., Kaifuchi, N., Mizuhara, Y., Warabi, E., Ohbuchi, K. and Mizoguchi, K. 2022. In vitro assessment of the inhibitory effect of goreisan extract and its ingredients on the P-glycoprotein drug transporter and cytochrome P-450 metabolic enzymes. Xenobiotica, 52: 511-519.
Terasawa, K. 2004. Evidence-based reconstruction of Kampo medicine: Part II-The concept of Sho. Evidence-Based Complementary and Alternative Medicine, 1: 119-123.
Watanabe, K., Matsuura, K., Gao, P., Hottenbacher, L., Tokunaga, H., Nishimura, K., Imazu, Y., Reissenweber, H. and Witt, C.M. 2011. Traditional Japanese Kampo medicine: Clinical research between modernity and traditional medicine-The state of research and methodological suggestions for the future. Evidence-Based Complementary and Alternative Medicine, 2011: 513842.
Weiss, J., Theile, D., Spalwisz, A., Burhenne, J., Riedel, K.D. and Haefeli, W.E. 2013. Influence of sildenafil and tadalafil on the enzyme- and transporter-inducing effects of bosentan and ambrisentan in LS180 cells. Biochemical Pharmacology, 85: 265-273.