博斯韦利亚·卡特利·伯德。树脂提取物诱导i期细胞色素P-450酶基因在人肝癌细胞中的表达:体外和硅细胞研究

IF 5.3 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Biologics : Targets & Therapy Pub Date : 2025-05-05 eCollection Date: 2025-01-01 DOI:10.2147/BTT.S491278
Sahar S Alghamdi, Hussah N Albahlal, Raghad Saleh Alajmi, Amani Alsharidah, Aljawharah Almogren, Rasha Suliman, Zeyad I Alehaideb
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引用次数: 0

摘要

简介:博斯韦利亚卡氏树脂(B. carteri)因其具有抗炎、伤口愈合和免疫调节等特性而被广泛认可。本研究考察了其水提取物在Hep G2细胞中调节关键细胞色素P450 (CYP)酶cyp1a2、CYP2B6和cyp3a4表达的能力,强调了药代动力学和毒理学意义。方法:对水提物进行内毒素污染和细胞毒性评价,以确定体外实验的适宜性。采用PCR法定量分析CYP酶基因表达。计算工具包括Protox-II、Swiss ADME和分子对接,用于评估药代动力学、CYP相互作用和生物靶点。竞争性结合试验研究了组成型雄甾受体(CAR)在CYP诱导中的作用。结果表明,几种代谢物,特别是熊去氧胆酸和β -谷甾醇,显示出与CYP酶的潜在相互作用,其中熊去氧胆酸显示出对CYP产生生物效应的可能性最高,并且与组成型雄甾烷受体(CAR)具有很强的结合亲和力。此外,一项受体竞争结合试验表明,CYP 2B6和3A4诱导的主要机制是通过激活CAR受体,尽管还需要进一步的证实研究。讨论:通过CAR受体激活观察到的CYP酶诱导符合USFDA关于CYP研究的指南。然而,熊去氧胆酸的潜在肝毒性和其他代谢物的相关毒性风险强调了谨慎的必要性。这些发现强调了草药相互作用的潜力,特别是与CYP酶代谢的药物。结论:综上所述,布氏杆菌树脂与CYP酶代谢的药物存在相互作用的可能;因此,我们建议消费者、患者和医疗保健提供者谨慎使用它们。虽然我们的发现提供了有价值的见解,但进一步的体内研究对于验证B. carteri对CYP基因表达的调节作用是必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Boswellia carteri Birdw. Resin Extract Induces Phase-I Cytochrome P-450 Enzyme Gene Expressions in Human Hepatocarcinoma (Hep G2) Cells: In vitro and in silico Studies.

Introduction: Boswellia carteri (B. carteri) resin is widely recognized for its anti-inflammatory, wound-healing, and immunomodulatory properties. This study examines the ability of its aqueous extracts to modulate the expression of key cytochrome P450 (CYP) enzymes-CYP1A2, CYP2B6, and CYP3A4-in Hep G2 cells, emphasizing pharmacokinetic and toxicological implications.

Methods: Aqueous extracts were evaluated for endotoxin contamination and cytotoxicity to ensure suitability for in vitro experimentation. PCR analysis was employed to quantify CYP enzyme gene expression. Computational tools, including Protox-II, Swiss ADME, and molecular docking, were used to assess pharmacokinetics, CYP interactions, and biological targets. Competitive binding assays were performed to investigate the involvement of the constitutive androstane receptor (CAR) in CYP induction.

Results: The results suggest that several metabolites, particularly ursodeoxycholic acid and beta-sitosterol, show potential interactions with CYP enzymes, with ursodeoxycholic acid demonstrating the highest probability of biological effects on CYP and a strong binding affinity to the Constitutive Androstane Receptor (CAR). Moreover, a receptor competitive binding assay suggested that the primary mechanism of CYP 2B6 and 3A4 induction is through activation of the CAR receptor although additional confirmatory studies are necessary.

Discussion: The observed CYP enzyme induction through CAR receptor activation aligns with USFDA guidelines for CYP studies. However, the hepatotoxic potential of ursodeoxycholic acid and the associated toxicity risks of other metabolites underscore the need for caution. The findings highlight the potential for herb-drug interactions, particularly with pharmaceuticals metabolized by CYP enzymes.

Conclusion: In conclusion, there is a potential for interactions between B. carteri resins and pharmaceuticals metabolized by CYP enzymes; thus, we advise caution to consumers, patients, and healthcare providers regarding their concomitant use. Although our findings provide valuable insights, further in vivo studies are essential to validate the modulatory effects of B. carteri on CYP gene expression.

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来源期刊
Biologics : Targets & Therapy
Biologics : Targets & Therapy MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
8.30
自引率
0.00%
发文量
22
审稿时长
16 weeks
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