{"title":"人肝脏微粒体中 CYP2C9、2D6 和 3A4 的 Physcion 抑制作用。","authors":"Lu Liu, Sen Sun, Xiaohua Li","doi":"10.1080/13880209.2024.2314089","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>The effect of the active ingredients in traditional Chinese medicines on the activity of cytochrome P450 enzymes (CYP450s) is a critical factor that should be considered in TCM prescriptions. Physcion, the major active ingredient of <i>Rheum</i> spp. (Polygonaceae), possesses wide pharmacological activities.</p><p><strong>Objectives: </strong>The effect of physcion on CYP450 activity was investigated to provide a theoretical basis for use.</p><p><strong>Materials and methods: </strong>The experiments were conducted in pooled human liver microsomes (HLMs). The activity of CYP450 isoforms was evaluated with corresponding substrates and probe reactions. Blank HLMs were set as negative controls, and typical inhibitors were employed as positive controls. The inhibition model was fitted with Lineweaver Burk plots. The concentration (0, 2.5, 5, 10, 25, 50 and 100 μM physcion) and time-dependent (0, 5, 10, 15 and 30 min) effects of physcion were also assessed.</p><p><strong>Results: </strong>Physcion suppressed CYP2C9, 2D6 and 3A4 in a concentration-dependent manner with IC<sub>50</sub> values of 7.44, 17.84 and 13.50 μM, respectively. The inhibition of CYP2C9 and 2D6 was competitive with the <i>K<sub>i</sub></i> values of 3.69 and 8.66 μM, respectively. The inhibition of CYP3A4 was non-competitive with a <i>K<sub>i</sub></i> value of 6.70 μM. Additionally, only the inhibition of CYP3A4 was time-dependent with the <i>K<sub>I</sub></i> and <i>K<sub>inact</sub></i> parameters of 3.10 μM<sup>-1</sup> and 0.049 min<sup>-1</sup>, respectively.</p><p><strong>Conclusions: </strong>The inhibition of CYP450s by physcion should be considered in its clinical prescription, and the study design can be employed to evaluate the interaction of CYP450s with other herbs.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"207-213"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868446/pdf/","citationCount":"0","resultStr":"{\"title\":\"Physcion inhibition of CYP2C9, 2D6 and 3A4 in human liver microsomes.\",\"authors\":\"Lu Liu, Sen Sun, Xiaohua Li\",\"doi\":\"10.1080/13880209.2024.2314089\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>The effect of the active ingredients in traditional Chinese medicines on the activity of cytochrome P450 enzymes (CYP450s) is a critical factor that should be considered in TCM prescriptions. Physcion, the major active ingredient of <i>Rheum</i> spp. (Polygonaceae), possesses wide pharmacological activities.</p><p><strong>Objectives: </strong>The effect of physcion on CYP450 activity was investigated to provide a theoretical basis for use.</p><p><strong>Materials and methods: </strong>The experiments were conducted in pooled human liver microsomes (HLMs). The activity of CYP450 isoforms was evaluated with corresponding substrates and probe reactions. Blank HLMs were set as negative controls, and typical inhibitors were employed as positive controls. The inhibition model was fitted with Lineweaver Burk plots. The concentration (0, 2.5, 5, 10, 25, 50 and 100 μM physcion) and time-dependent (0, 5, 10, 15 and 30 min) effects of physcion were also assessed.</p><p><strong>Results: </strong>Physcion suppressed CYP2C9, 2D6 and 3A4 in a concentration-dependent manner with IC<sub>50</sub> values of 7.44, 17.84 and 13.50 μM, respectively. The inhibition of CYP2C9 and 2D6 was competitive with the <i>K<sub>i</sub></i> values of 3.69 and 8.66 μM, respectively. The inhibition of CYP3A4 was non-competitive with a <i>K<sub>i</sub></i> value of 6.70 μM. Additionally, only the inhibition of CYP3A4 was time-dependent with the <i>K<sub>I</sub></i> and <i>K<sub>inact</sub></i> parameters of 3.10 μM<sup>-1</sup> and 0.049 min<sup>-1</sup>, respectively.</p><p><strong>Conclusions: </strong>The inhibition of CYP450s by physcion should be considered in its clinical prescription, and the study design can be employed to evaluate the interaction of CYP450s with other herbs.</p>\",\"PeriodicalId\":19942,\"journal\":{\"name\":\"Pharmaceutical Biology\",\"volume\":\"62 1\",\"pages\":\"207-213\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868446/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13880209.2024.2314089\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13880209.2024.2314089","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/14 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Physcion inhibition of CYP2C9, 2D6 and 3A4 in human liver microsomes.
Context: The effect of the active ingredients in traditional Chinese medicines on the activity of cytochrome P450 enzymes (CYP450s) is a critical factor that should be considered in TCM prescriptions. Physcion, the major active ingredient of Rheum spp. (Polygonaceae), possesses wide pharmacological activities.
Objectives: The effect of physcion on CYP450 activity was investigated to provide a theoretical basis for use.
Materials and methods: The experiments were conducted in pooled human liver microsomes (HLMs). The activity of CYP450 isoforms was evaluated with corresponding substrates and probe reactions. Blank HLMs were set as negative controls, and typical inhibitors were employed as positive controls. The inhibition model was fitted with Lineweaver Burk plots. The concentration (0, 2.5, 5, 10, 25, 50 and 100 μM physcion) and time-dependent (0, 5, 10, 15 and 30 min) effects of physcion were also assessed.
Results: Physcion suppressed CYP2C9, 2D6 and 3A4 in a concentration-dependent manner with IC50 values of 7.44, 17.84 and 13.50 μM, respectively. The inhibition of CYP2C9 and 2D6 was competitive with the Ki values of 3.69 and 8.66 μM, respectively. The inhibition of CYP3A4 was non-competitive with a Ki value of 6.70 μM. Additionally, only the inhibition of CYP3A4 was time-dependent with the KI and Kinact parameters of 3.10 μM-1 and 0.049 min-1, respectively.
Conclusions: The inhibition of CYP450s by physcion should be considered in its clinical prescription, and the study design can be employed to evaluate the interaction of CYP450s with other herbs.
期刊介绍：
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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