邢盼盼 吴文华 杜 鹏 韩凤梅 陈 勇. 马钱子碱与甘草次酸、甘草苷配伍后对大鼠肝脏CYP450的影响(英文)J. 药学学报, 2011,46(5): 573-580.
引用本文: 邢盼盼 吴文华 杜 鹏 韩凤梅 陈 勇. 马钱子碱与甘草次酸、甘草苷配伍后对大鼠肝脏CYP450的影响(英文)J. 药学学报, 2011,46(5): 573-580.
GENG Fen-Fen, Tun-Wen-Hua, Du- Feng, Han-Feng-Mei, Chen- Yong. Effects of brucine combined with glycyrrhetinic acid or liquiritin on rat hepatic cytochrome P450 activities in vivoJ. 药学学报, 2011,46(5): 573-580.
Citation: GENG Fen-Fen, Tun-Wen-Hua, Du- Feng, Han-Feng-Mei, Chen- Yong. Effects of brucine combined with glycyrrhetinic acid or liquiritin on rat hepatic cytochrome P450 activities in vivoJ. 药学学报, 2011,46(5): 573-580.

马钱子碱与甘草次酸、甘草苷配伍后对大鼠肝脏CYP450的影响(英文)

Effects of brucine combined with glycyrrhetinic acid or liquiritin on rat hepatic cytochrome P450 activities in vivo

  • 摘要:

    马钱子碱每日低、中、高 (3, 1560 mg·kg−1) 剂量以及高剂量马钱子碱和甘草次酸 (每日25 mg·kg−1)甘草苷 (每日20 mg·kg−1) 配伍, 分别对Wistar大鼠连续灌胃给药7天后, 检测不同给药组对CYP3ACYP1A2CYP2E1CYP2C的酶活性和mRNA表达的影响。与对照组相比, 高剂量马钱子碱使CYP3A活性下降24.5%, CYP2C的活性下降34.6%, 而使CYP2E1的活性提高了146.1%。另一方面, 与高剂量组相比, 甘草次酸配伍组使CYP2E1的活性降低了51.4%, CYP1A2的活性降低了33.5%; 甘草苷配伍组使CYP2E1的活性降低了41.1%, CYP2C的活性降低了37.7%。实验结果表明, 马钱子碱和甘草次酸、甘草苷配伍后, 可以在一定程度上影响上述CYP450酶的mRNA表达和酶活性。因此推测配伍后甘草苷对马钱子碱所致CYP450酶异常变化的拮抗作用, 以及甘草次酸对CYP2E1CYP1A2活性的抑制作用, 可能是甘草降低马钱子毒性的重要机制之一。

     

    Abstract:

    The activities of four CYP450 enzymes (CYP3A, 1A2, 2E1 and 2C) and the mRNA expression levels of CYP1A2, 2E1, 2C11 and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg·kg−1 per day) and the high dose of BR combined with glycyrrhetinic acid (GA, 25 mg·kg−1 per day) or liquiritin (LQ, 20 mg·kg−1 per day) for 7 consecutive days.  Compared with the control, brucine caused 24.5% and 34.6% decrease of CYP3A-associated testosterone 6β-hydroxylation (6βTesto-OH) and CYP2C-associated tolbutamide hydroxylation (Tol-OH), respectively, and 146.1% increase of CYP2E1-associated para-nitrophenol hydroxylation (PNP-OH) at the high dose level.  On the other hand, (BR+GA) caused 51.4% and 33.5% decrease, respectively, of CYP2E1-associated PNP-OH and CYP1A2-associated ethoxyresoru?n-O-de-ethylation (EROD) as compared with the high dose of BR group.  Meanwhile, (BR+LQ) caused 41.1% decrease of CYP2E1-associated PNP-OH and 37.7% increase of CYP2C- associated Tol-OH.  The results indicated that the co-administration of BR with GA or LQ had effect on mRNA expression and activities of the CYP450 enzymes mentioned above to some extent, and the in vivo antagonism of LQ on BR-induced CYPs adverse effects and the in vivo inhibitory action of GA on CYP2E1 and 1A2 might play an important role in the detoxification of Radix Glycyrrhizae against Strychnos nux-vomica L.

     

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