School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Tianjin 300193, Nankai District, China.
BMC Complement Altern Med. 2014 Aug 18;14:306. doi: 10.1186/1472-6882-14-306.
Yanhusuo (Corydalis yanhusuo W.T. Wang; YHS), is a well-known traditional Chinese herbal medicine, has been used in China for treating pain including chest pain, epigastric pain, and dysmenorrhea. Its alkaloid ingredients including tetrahydropalmatine are reported to inhibit cytochromes P450 (CYPs) activity in vitro. The present study is aimed to assess the potential of total alkaloid extract (TAE) from YHS to effect the activity and mRNA levels of five cytochromes P450 (CYPs) in rat.
Rats were administered TAE from YHS (0, 6, 30, and 150 mg/kg, daily) for 14 days, alanine aminotransferase (ALT) levels in serum were assayed, and hematoxylin and eosin-stained sections of the liver were prepared for light microscopy. The effects of TAE on five CYPs activity and mRNA levels were quantitated by cocktail probe drugs using a rapid chromatography/tandem mass spectrometry (LC-MS/MS) method and reverse transcription-polymerase chain reaction (RT-PCR), respectively.
In general, serum ALT levels showed no significant changes, and the histopathology appeared largely normal compared with that in the control rats. At 30 and 150 mg/kg TAE dosages, an increase in liver CYP2E1 and CYP3A1 enzyme activity were observed. Moreover, the mRNA levels of CYP2E1 and CYP3A1 in the rat liver, lung, and intestine were significantly up-regulated with TAE from 6 and 30 mg/kg, respectively. Furthermore, treatment with TAE (150 mg/kg) enhanced the activities and the mRNA levels of CYP1A2 and CYP2C11 in rats. However, the activity or mRNA level of CYP2D1 remained unchanged.
These results suggest that TAE-induced CYPs activity in the rat liver results from the elevated mRNA levels of CYPs. Co-administration of prescriptions containing YHS should consider a potential herb (drug)-drug interaction mediated by the induction of CYP2E1 and CYP3A1 enzymes.
延胡索（Corydalis yanhusuo W.T. Wang；YHS）是一种著名的中药，在中国一直被用于治疗胸痛、上腹疼痛和痛经等疼痛。其生物碱成分包括延胡索乙素被报道可在体外抑制细胞色素 P450（CYPs）的活性。本研究旨在评估延胡索总生物碱提取物（TAE）对大鼠 5 种细胞色素 P450（CYPs）活性和 mRNA 水平的潜在影响。
大鼠给予延胡索总生物碱提取物（YHS）（0、6、30 和 150 mg/kg，每日）14 天，检测血清丙氨酸氨基转移酶（ALT）水平，并用苏木精-伊红染色法制备肝组织切片，进行光镜检查。采用快速色谱/串联质谱（LC-MS/MS）法和逆转录-聚合酶链反应（RT-PCR）法分别定量检测 TAE 对 5 种 CYP 活性和 mRNA 水平的影响。
一般来说，血清 ALT 水平无明显变化，与对照组大鼠相比，组织病理学变化基本正常。在 30 和 150 mg/kg TAE 剂量下，观察到肝 CYP2E1 和 CYP3A1 酶活性增加。此外，从 6 和 30 mg/kg 开始，大鼠肝、肺和肠中 CYP2E1 和 CYP3A1 的 mRNA 水平显著上调。此外，用 TAE（150 mg/kg）处理可增强大鼠 CYP1A2 和 CYP2C11 的活性和 mRNA 水平。然而，CYP2D1 的活性或 mRNA 水平保持不变。
这些结果表明，TAE 诱导大鼠肝 CYP 活性是由于 CYP 升高所致。含 YHS 的方剂联合用药时，应考虑 CYP2E1 和 CYP3A1 酶诱导引起的潜在药物相互作用。
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