Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may gi...
Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.
Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.
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제안 방법
Although there have been studies that investigated the modulatory effects of several ginsenosides on CYP activities, there are not enough reports to compare the effects of individual ginsenosides on CYP enzyme inhibition in HLMs. In this study, we investigated the inhibitory effects of 12 ginsenosides on seven CYP isoforms in HLMs using cassette assay/ LC-MS/MS.
In this study, we used liquid chromatography-triple quadrupole mass spectrometer system in MRM mode to determine the activities of seven CYPs in HLMs simultaneously, using cocktail substrates. The cocktail probes consisted of selective seven substrates for each CYP; phenacetin for CYP1A2, coumarin for CYP2A6, bupropion for CYP2B6, diclofenac for CYP2C9, omeprazole for CYP2C19, dextromethorphan for CYP2D6, and midazolam for CYP3A4 .
In this study, we used liquid chromatography-triple quadrupole mass spectrometer system in MRM mode to determine the activities of seven CYPs in HLMs simultaneously, using cocktail substrates. The cocktail probes consisted of selective seven substrates for each CYP; phenacetin for CYP1A2, coumarin for CYP2A6, bupropion for CYP2B6, diclofenac for CYP2C9, omeprazole for CYP2C19, dextromethorphan for CYP2D6, and midazolam for CYP3A4 . After incubation, the amount of generated metabolites was determined by area ratio (metabolite/IS area) to quantify the activity of CYP isoforms.
대상 데이터
The LC system consisted of a G1312A binary pump (Cohesion Technologies, CA, USA), G1322A degasser, 1100 series COLCOM (Agilent, USA), and 1100 series auto-sampler. A Kinetex® C18 column (2.
The ginsenosides Rb1, Rb2, Rc, Rd, F2, K, Rg3, F1, Rg1, Rh1, Rf, and Re were obtained from Ambo Institute (Daejeon, South Korea; Figure 1). Pooled HLMs (mixed gender) were purchased from Sekisui XenoTech, LLC.
성능/효과
In conclusion, we investigated the inhibitory effects of 12 purified ginsenosides on the activities of seven CYPs using LC-MS/MS. Although several ginsenosides showed inhibitory effects on CYP enzymes in HLMs, it cannot be linked to herb-drug interaction in vivo owing to the low bioavailability of ginsenosides.
15,18 Moreover, ginsenoside F2 is the precursor component of compound K generated from ginsenosides Rb1 and Rd.3 In this study, ginsenoside F2 showed strong inhibitory effects, while Rb2, Rd, Rg3, F1, and compound K showed weak inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation.
참고문헌 (23)
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