Mona H Haron, Olivia Dale, Katherine Martin, Bharathi Avula, Amar G Chittiboyina, Ikhlas A Khan, Bill J Gurley, Shabana I Khan
{"title":"根据 PXR 和 AhR 对 CYP3A4 和 CYP1A2 的影响,评估美国市场上常用植物药的草药-药物相互作用潜力。","authors":"Mona H Haron, Olivia Dale, Katherine Martin, Bharathi Avula, Amar G Chittiboyina, Ikhlas A Khan, Bill J Gurley, Shabana I Khan","doi":"10.1080/19390211.2022.2110351","DOIUrl":null,"url":null,"abstract":"<p><p>In this study, hydroethanolic extracts of 30 top-selling botanicals (herbs) commonly used as ingredients of herbal dietary supplements in the US were screened for their potential to activate the human pregnane X receptor (hPXR) and human aryl hydrocarbon receptor (hAhR) and to increase the activities of hPXR- and hAhR-regulated drug metabolizing cytochrome P450 enzymes (i.e., CYP3A4 and CYP1A2, respectively). Of the 30 botanicals tested, 21 induced PXR and 29 induced AhR transcriptional activities. Out of the 21 botanicals that induced hPXR transcriptional activity, 14 yielded >50% induction in CYP3A4 activity at concentrations ranging from 6 to 60 µg/mL and 16 out of the 29 botanicals that activated hAhR yielded >50% induction in CYP1A2 activity at concentrations ranging from 3 to 30 µg/mL. Moreover, eight botanicals (<i>G. gummi-gutta</i> [garcinia], Hemp [low and high CBD content], <i>H. perforatum</i> [St. John's wort], <i>M. vulgare</i> [horehound], <i>M. oleifera</i> [moringa], <i>O. vulgare</i> [oregano], <i>P. johimbe</i> [yohimbe] and <i>W. somnifera</i> [ashwagandha]) yielded >50% induction in both CYP3A4 and CYP1A2 activity. Herbal products are mixtures of phytoconstituents, any of which could modulate drug metabolism. Our data reveals that several top-selling botanicals may pose herb-drug interaction (HDI) risks <i>via</i> CYP450 induction. While <i>in vitro</i> experiments can provide useful guidance in assessing a botanical's HDI potential, their clinical relevance needs to be investigated <i>in vivo</i>. Botanicals whose effects on hPXR/CYP3A4, and hAhR/CYP1A2 activity were most pronounced will be slated for further clinical investigation.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2.\",\"authors\":\"Mona H Haron, Olivia Dale, Katherine Martin, Bharathi Avula, Amar G Chittiboyina, Ikhlas A Khan, Bill J Gurley, Shabana I Khan\",\"doi\":\"10.1080/19390211.2022.2110351\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In this study, hydroethanolic extracts of 30 top-selling botanicals (herbs) commonly used as ingredients of herbal dietary supplements in the US were screened for their potential to activate the human pregnane X receptor (hPXR) and human aryl hydrocarbon receptor (hAhR) and to increase the activities of hPXR- and hAhR-regulated drug metabolizing cytochrome P450 enzymes (i.e., CYP3A4 and CYP1A2, respectively). Of the 30 botanicals tested, 21 induced PXR and 29 induced AhR transcriptional activities. Out of the 21 botanicals that induced hPXR transcriptional activity, 14 yielded >50% induction in CYP3A4 activity at concentrations ranging from 6 to 60 µg/mL and 16 out of the 29 botanicals that activated hAhR yielded >50% induction in CYP1A2 activity at concentrations ranging from 3 to 30 µg/mL. Moreover, eight botanicals (<i>G. gummi-gutta</i> [garcinia], Hemp [low and high CBD content], <i>H. perforatum</i> [St. John's wort], <i>M. vulgare</i> [horehound], <i>M. oleifera</i> [moringa], <i>O. vulgare</i> [oregano], <i>P. johimbe</i> [yohimbe] and <i>W. somnifera</i> [ashwagandha]) yielded >50% induction in both CYP3A4 and CYP1A2 activity. Herbal products are mixtures of phytoconstituents, any of which could modulate drug metabolism. Our data reveals that several top-selling botanicals may pose herb-drug interaction (HDI) risks <i>via</i> CYP450 induction. While <i>in vitro</i> experiments can provide useful guidance in assessing a botanical's HDI potential, their clinical relevance needs to be investigated <i>in vivo</i>. Botanicals whose effects on hPXR/CYP3A4, and hAhR/CYP1A2 activity were most pronounced will be slated for further clinical investigation.</p>\",\"PeriodicalId\":15646,\"journal\":{\"name\":\"Journal of Dietary Supplements\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Dietary Supplements\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/19390211.2022.2110351\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/8/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Dietary Supplements","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/19390211.2022.2110351","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/8/26 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2.
In this study, hydroethanolic extracts of 30 top-selling botanicals (herbs) commonly used as ingredients of herbal dietary supplements in the US were screened for their potential to activate the human pregnane X receptor (hPXR) and human aryl hydrocarbon receptor (hAhR) and to increase the activities of hPXR- and hAhR-regulated drug metabolizing cytochrome P450 enzymes (i.e., CYP3A4 and CYP1A2, respectively). Of the 30 botanicals tested, 21 induced PXR and 29 induced AhR transcriptional activities. Out of the 21 botanicals that induced hPXR transcriptional activity, 14 yielded >50% induction in CYP3A4 activity at concentrations ranging from 6 to 60 µg/mL and 16 out of the 29 botanicals that activated hAhR yielded >50% induction in CYP1A2 activity at concentrations ranging from 3 to 30 µg/mL. Moreover, eight botanicals (G. gummi-gutta [garcinia], Hemp [low and high CBD content], H. perforatum [St. John's wort], M. vulgare [horehound], M. oleifera [moringa], O. vulgare [oregano], P. johimbe [yohimbe] and W. somnifera [ashwagandha]) yielded >50% induction in both CYP3A4 and CYP1A2 activity. Herbal products are mixtures of phytoconstituents, any of which could modulate drug metabolism. Our data reveals that several top-selling botanicals may pose herb-drug interaction (HDI) risks via CYP450 induction. While in vitro experiments can provide useful guidance in assessing a botanical's HDI potential, their clinical relevance needs to be investigated in vivo. Botanicals whose effects on hPXR/CYP3A4, and hAhR/CYP1A2 activity were most pronounced will be slated for further clinical investigation.
期刊介绍:
The Journal of Dietary Supplements (formerly the Journal of Nutraceuticals, Functional & Medical Foods) has been retitled to reflect the bold departure from a traditional scientific journal presentation to a leading voice for anyone with a stake in dietary supplements. The journal addresses important issues that meet the broad range of interests from researchers, regulators, marketers, educators, and health professionals from academic, governmental, industry, healthcare, public health, and consumer education sectors. This vital tool not only presents scientific information but interprets it - helping you more readily pass it on to your students, patients, clients, or company.