• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.143-146
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• 2011

Scutellariae Radix is widely used in the traditional herbal medicine for the treatment of fever, cough, dysentery, hepatitis and hypertension in Korea, China and Japan. In this study, we investigated the effects of 70% ethanolic extract of Scutellariae Radix (SRE) on CYP450-mediated drug metabolism in the in vitro systems using human liver microsomes and hepatocytes. The microsomal incubation assay showed that SRE inhibited the drug metabolism reactions catalyzed by CYP1A2, CYP2C8 and CYP2C9 in a dose-dependent manner. In particular, SRE was shown to strongly inhibit the metabolic activity of CYP1A2 with an $IC_{50}$ value of 4.6 ${\mu}g/mL$. When SRE was evaluated for its effect on the induction of CYP450 enzyme activities in cryopreserved human hepatocytes, SRE did not exhibit any effect.

• Journal of Sasang Constitutional Medicine
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• v.24 no.4
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• pp.84-91
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• 2012

Objectives : The purpose of this study is to investigate the inhibitory or inductive potentials of Yuldahanso-tang (YDT) and Chungsimyonja-tang (CST), herbal formulas for Taeeumin, on cytochrome P450 (CYP450) drug metabolizing enzyme. The mechanisms for the herbal formula-drug interaction has not been well reported in spite of the chance for co-administration with conventional drugs. Methods : To evaluate the interaction potential of YDT-drug or CST-drug, the fluorescence-based enzyme assays on CYP450 isozymes including CYP3A4, CYP2C19, CYP2D6 and CYP2E1 were established in vitro. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results : YDT showed inhibitory effects on CYP2D6 and CYP2E1-mediated metabolism, while it exhibited week inhibition on CYP3A4 and CYP2C19 relatively. CST exerted relatively weak inhibitory effects on the four CYP450 isozymes compared to that of YDT. Conclusions : These results suggest that the herbal formula-drug interaction could be occur when YDT are co-administered with drugs mediated by CYP2D6 or CYP2E1.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.201-206
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• 2015

Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated $IC_{50}$ values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.

• The Korea Journal of Herbology
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• v.33 no.6
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• pp.9-18
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• 2018

Objective : Many patients take antihypertensive drugs as well as herbal medicines at the same time in order to treat other symptoms or to keep their well-being. In this study, interactions between herbal medicines and synthetic antihypertensive drugs were analyzed. Methods : To investigate the interaction between herbal medicines and synthetic antihypertensive drugs, three electronic databases, including OASIS, Mediline and Sciencedirect were searched. Experimental and clinical studies on the interaction between herbal medicines and antihypertensive drugs were independently reviewed and included. Results : Analyzing selected studies, twenty herbs were found to interact with antihypertensive drugs. Herbs found to increase the antihypertensive effect were Panax ginseng, Carthamus tinctorius, Magnolia officinalis, Silybum marianum, Scutellaria baicalensis, Schisandra chinensis, Sophora flavescens, Piper nigrum, Curcuma longa, Ginkgo biloba, Juncus effuses and Hydrastis canadensis. In contrast, Commiphora myrrha, Rhodiola rosea, Hypericum perforatum, Eurycoma longifolia, and Daturae metel were found to inhibit the antihypertensive effect. Stephania tetrandra could increase or decrease the effect depending on the type of antihypertensive drug. Epedria sínica was suspected of pharmacodynamic interaction with antihypertensive drug. Glycyrrhiza uralensis has been reported to have serious side effects in combination with antihypertensive drugs. Conclusion : These results imply that when used in combination with herbal medicines and synthetic antihypertensive drugs, proper doses and herbs which are to avoid need to be informed to the patients. Despite concerns about interactions between herbal medicines and synthetic drugs, related research is very limited. More systematic researches are needed to give information on patient safety as well as to guide clinical practice.

• The Journal of Korean Medicine
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• v.35 no.2
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• pp.47-59
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• 2014

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.

• BMB Reports
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• v.55 no.9
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• pp.417-428
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• 2022

Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.

• Mass Spectrometry Letters
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• v.14 no.3
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• pp.116-119
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• 2023

Gynostemma pentaphyllum (Thunb.) Makino extract, a natural product with a history of traditional use, has gained attention for its potential health benefits. This study aimed to investigate its effects on key cytochrome P450 (CYP) enzymes using LC-MS/MS. Human liver microsomes and cDNA-expressed CYP2C8, CYP2C9, CYP2C19, and CYP3A4 supersomes were employed. Enzyme activity was assessed based on the formation of CYP-specific marker metabolites. The resulting data showed that the extract exhibited inhibitory effects on CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Thus, G. pentaphyllum extract may influence the pharmacokinetics of drugs metabolized by CYP2C8, CYP2C9, CYP2C19, and CYP3A4. These findings emphasize the importance of considering potential herb-drug interactions when incorporating this extract into therapeutic regimens or dietary supplements.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.385.3-386
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• 2002

Current therapeutics for osteoporosis are often associated with adverse effects with long-term use. The purpose of this study was to find out herbal drug interaction and to apply an alternative drug candidate for osteoporosis based on a traditional medicinal herb that may have fewer side effects and less uterine hypertrophy. Effect of 219-H. a mixed herbal extract including Astragali Radix. was investigated on osteoporosis in vitro and in vivo models. (omitted)

• YAKHAK HOEJI
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• v.59 no.2
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• pp.49-54
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• 2015

In the present study we evaluated comparative herb-drug interaction potential of red ginseng total powder, ginsenoside Rg1, and Rb1 by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, red ginseng total powder inhibited significantly activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and testosterone 6-beta hydroxylation by CYP3A4, but the $IC_{50}$ values were higher than $556{\mu}g/ml$. Activities of CYP2B6, CYP2C9, CYP2D6 and CYP3A4 were inhibited by ginsenoside Rb1. Also, activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and testosterone 6-beta hydroxylation by CYP3A4 were inhibited by ginsenoside Rg1. The $IC_{50}$ values of ginsenoside Rb1 and Rg1 were higher than $200{\mu}g/ml$. Based on $IC_{50}$ values against CYP isoforms, ginsenosides-drug interactions by CYP inhibition may be very low in clinical situations.

• Toxicological Research
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• v.32 no.3
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• pp.207-213
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• 2016

Although propolis is one of the most popular functional foods for human health, there have been no comprehensive studies of herb-drug interactions through cytochrome P450 (CYP) inhibition. The purpose of this study was to determine the inhibitory effects of propolis on the activities of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 using pooled human liver microsomes (HLMs). Propolis inhibited CYP1A2, CYP2E1 and CYP2C19 with an $IC_{50}$ value of 6.9, 16.8, and $43.1{\mu}g/mL$, respectively, whereas CYP2A6, 2B6, 2C9, 2D6, and 3A4 were unaffected. Based on half-maximal inhibitory concentration shifts between microsomes incubated with and without nicotinamide adenine dinucleotide phosphate, propolis-induced CYP1A2, CYP2C19, and CYP2E1 inhibition was metabolism-independent. To evaluate the interaction potential between propolis and therapeutic drugs, the effects of propolis on metabolism of duloxetine, a serotonin-norepinephrine reuptake inhibitor, were determined in HLMs. CYP1A2 and CYP2D6 are involved in hydroxylation of duloxetine to 4-hydroxy duloxetine, the major metabolite, which was decreased following propolis addition in HLMs. These results raise the possibility of interactions between propolis and therapeutic drugs metabolized by CYP1A2.