دورية أكاديمية

Involvement of NF-κB in the reversal of CYP3A down-regulation induced by sea buckthorn in BCG-induced rats.

التفاصيل البيبلوغرافية
العنوان: Involvement of NF-κB in the reversal of CYP3A down-regulation induced by sea buckthorn in BCG-induced rats.
المؤلفون: Fengting Liu, Tao Wang, Xiaoxia Li, Jinxue Jia, Qin Lin, Yongzhi Xue
المصدر: PLoS ONE, Vol 15, Iss 9, p e0238810 (2020)
بيانات النشر: Public Library of Science (PLoS), 2020.
سنة النشر: 2020
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Previous studies reported that sea buckthorn (Hippophae rhamnoides L., Elaeagnaceae, HRP) exhibits hepatoprotective effects via its anti-inflammatory and antioxidant properties as well as its inhibitory effects on collagen synthesis. However, it is unclear whether this hepatoprotective effect is also achieved by regulating liver drug metabolism enzyme pathways. Herein, we examined the regulatory effect of HRP on cytochrome P450 3A (CYP3A) in rats with immune liver injury, and explored the molecular mechanism of its hepatoprotective effect. Rat models of immunological liver injury were induced by intravenous injections of Bacillus Calmette-Guerin (BCG; 125 mg kg-1; 2 wks). Specific protein levels were detected by ELISA or western blot, and CYP3A mRNA expression was detected by RT-PCR. High-performance liquid chromatography (HPLC) detected relative changes in CYP3A metabolic activity based on the rates of 1-hydroxylation of the probe drug midazolam (MDZ). BCG pretreatment (125 mg kg-1) significantly down-regulated liver CYP3A protein expression compared with the control, metabolic activity, and transcription levels while up-regulating liver NF-κB, IL-1β, TNF-α and iNOS. HRP intervention (ED50: 78 mg kg-1) moderately reversed NF-κB, inflammatory cytokines, and iNOS activation in a dose-dependent manner (P < 0.05), and suppressed CYP3A down-regulation (P < 0.05); thereby partially alleviating liver injury. During immune liver injury, HRP may reverse CYP3A down-regulation by inhibiting NF-κB signal transduction, and protect liver function, which involves regulation of enzymes transcriptionally, translationally and post-translationally. The discovery that NF-κB is a molecular target of HRP may initiate the development and optimization of a clinical therapeutic approach to mitigate hepatitis B and other immunity-related liver diseases.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0238810
URL الوصول: https://doaj.org/article/1e7fd1a35c404f2d82bd161ca6746268
رقم الأكسشن: edsdoj.1e7fd1a35c404f2d82bd161ca6746268
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0238810