Panax ginseng Inhibits Metabolism of Diester Alkaloids by Downregulating CYP3A4 Enzyme Activity via the Pregnane X Receptor
المؤلفون المشاركون
Ma, Zengchun
Gao, Yue
Huang, Guang-yao
Yang, Liang
Wang, Yuguang
Xu, Huanhua
Zhang, Zhaoyan
المصدر
Evidence-Based Complementary and Alternative Medicine
العدد
المجلد 2019، العدد 2019 (31 ديسمبر/كانون الأول 2019)، ص ص. 1-13، 13ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2019-03-21
دولة النشر
مصر
عدد الصفحات
13
التخصصات الرئيسية
الملخص EN
To investigate the effects of P.
ginseng C.A.
Mey (P.
ginseng) on the metabolism of diester alkaloids and explore the potential mechanism.
P.
ginseng was administered orally to rats for 7 days, after which liver microsome samples were prepared and then incubated with diester alkaloids.
Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to determinate the concentration of diester alkaloids to calculate the clearance rate.
The cocktail method was used to evaluate the effects of oral administration of P.
ginseng extracts on the activities of cytochrome P450 (CYP) isoforms in rats through the changes in the pharmacokinetic parameters of the probe drugs.
The protein and gene expression of CYP3A2 and pregnane X receptor (PXR) in rats were evaluated by western blotting and quantitative PCR.
The specific enzyme inhibitor method and human recombinant enzyme method were used to identify the involvement of sub-CYPs in the metabolism of diester alkaloids in human liver microsomes (HLMs).
The clearances of aconitine, mesaconitine, and hypaconitine in the P.
ginseng groups were lower than those of the control group.
The areas under the curve of midazolam were 2.37 ± 1.05, 4.96 ± 0.51, and 6.23 ± 1.30 mg·L−1·h for the low-, medium-, and high-dose P.
ginseng groups, respectively, which were higher than that of the control (2.23 ± 0.64 mg·L−1·h).
The clearances of midazolam for the medium- (1.87 ± 0.16 L·h−1·kg−1) and high-dose (1.60 ± 0.34 L·h−1·kg−1) P.
ginseng groups were lower than that of the control group (4.66 ± 1.43 L·h−1·kg−1).
After exposure to P.
ginseng extracts, the gene and protein expression levels of CYP3A4 and PXR were decreased.
The hepatic metabolism rates of aconitine, mesaconitine, and hypaconitine in HLMs were decreased to 60.37%, 21.67%, and 10.11%, respectively, when incubated with ketoconazole, a specific inhibitor for CYP3A.
The kinetic plots indicated that the KM and Vmax values of CYP3A4 were 10.08 ± 3.26 μM and 0.12 ± 0.01nmol·mg protein−1·min−1 for aconitine, 131.3 ± 99.75 μM and 0.73 ± 0.44 nmol·mg protein−1·min−1 for mesaconitine, and 17.05 ± 9.70 μM and 0.16 ± 0.04 nmol·mg protein−1·min−1 for hypaconitine, respectively.
The in vitro mean intrinsic clearance rates by CYP3A4 were 0.0119, 0.0056, and 0.0091 mL·nmol CYP−1·min−1 for aconitine, mesaconitine, and hypaconitine, respectively.
Therefore we implied that P.
ginseng inhibited the metabolism of diester alkaloids in vitro and decreased the CYP3A4 enzyme activity as well as the gene and protein expression of CYP3A4 and PXR in vivo.
CYP3A4 had a larger effect on diester alkaloid metabolism than the other human CYP isoforms, CYP1A2, CYP2C9, and CYP2E1.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Yang, Liang& Wang, Yuguang& Xu, Huanhua& Huang, Guang-yao& Zhang, Zhaoyan& Ma, Zengchun…[et al.]. 2019. Panax ginseng Inhibits Metabolism of Diester Alkaloids by Downregulating CYP3A4 Enzyme Activity via the Pregnane X Receptor. Evidence-Based Complementary and Alternative Medicine،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1149440
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Yang, Liang…[et al.]. Panax ginseng Inhibits Metabolism of Diester Alkaloids by Downregulating CYP3A4 Enzyme Activity via the Pregnane X Receptor. Evidence-Based Complementary and Alternative Medicine No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1149440
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Yang, Liang& Wang, Yuguang& Xu, Huanhua& Huang, Guang-yao& Zhang, Zhaoyan& Ma, Zengchun…[et al.]. Panax ginseng Inhibits Metabolism of Diester Alkaloids by Downregulating CYP3A4 Enzyme Activity via the Pregnane X Receptor. Evidence-Based Complementary and Alternative Medicine. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1149440
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1149440
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر