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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 48  |  Page : 241-252

Traditional herbal formulas to as treatments for musculoskeletal disorders: Their inhibitory effects on the activities of human microsomal cytochrome p450s and udp-glucuronosyltransferases


K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea

Correspondence Address:
Dr. Hyekyung Ha
K-herb Research Center, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon
Republic of Korea
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1296.192205

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Objective: The aim of this study was to assess the influence of traditional herbal formulas, including Bangpungtongseong-san (BPTSS; Fangfengtongsheng-san, Bofu-tsusho-san ), Ojeok-san (OJS; Wuji-san, Goshaku-san ), and Oyaksungi-san (OYSGS; Wuyaoshungi-san, Uyakujyunki-san ), on the activities of the human cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs), which are drug-metabolizing enzymes. Materials and Methods: The activities of the major human CYP450 isozymes (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were investigated using in vitro fluorescence-based and luminescence-based enzyme assays, respectively. The inhibitory effects of the herbal formulas were characterized, and their IC50values were determined. Results: BPTSS inhibited the activities of CYP1A2, CYP2C19, CYP2E1, and UGT1A1 while it exerted relatively weak inhibition on CYP2B6, CYP2C9, CYP2D6, and CYP3A4. BPTSS also negligibly inhibited the activities of UGT1A4 and UGT2B7, with IC50values in the excess of 1000 μg/mL. OJS and OYSGS inhibited the activity of CYP2D6, whereas they exhibited no inhibition of the UGT1A4 activity at doses <1000 μg/mL. In addition, OJS inhibited the CYP1A2 activity but exerted a relatively weak inhibition on the activities of CYP2C9, CYP2C19, CYP2E1, and CYP3A4. Conversely, OJS negligibly inhibited the activities of CYP2B6, UGT1A1, and UGT2B7 with IC50values in excess of 1000 μg/mL. OYSGS weakly inhibited the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4, and UGT1A1, with a negligible inhibition on the activities of CYP2B6, CYP2C9, and UGT2B7, with IC50values in excess of 1000 μg/mL. Conclusions: These results provide information regarding the safety and effectiveness of BPTSS, OJS, and OYSGS when combined with conventional drugs. Abbreviation used: BPTSS: Bangpungtongseong-san, OJS: Ojeok-san, OYSGS: Oyaksungi-san, CYP450s: cytochrome P450s, UGTs: UDP-glucuronosyltransferases, MSDs: Musculoskeletal disorders, NSAIDs: nonsteroidal anti-inflammatory drugs, EOMCC: 7-ethoxy-methyloxy-3-cyanocoumarin, DBOMF: di(benzyloxymethoxy)fluorescein, BOMCC: 7-benzyloxy-4-trifluoromethylcoumarin, HPLC: High-performance liquid chromatography, PDA: photo diode array, SEM: standard error of the mean, UDPGA: uridine 5'-diphosphoglucuronic acid.


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