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四种线性呋喃香豆素(佛手柑内酯、花椒毒素、欧前胡素和花椒毒素)在小鼠最大电休克诱导的癫痫发作模型中的抗惊厥作用:比较研究。

Anticonvulsant effects of four linear furanocoumarins, bergapten, imperatorin, oxypeucedanin, and xanthotoxin, in the mouse maximal electroshock-induced seizure model: a comparative study.

机构信息

Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, PL 20-950 Lublin, Poland.

出版信息

Pharmacol Rep. 2010 Nov-Dec;62(6):1231-6. doi: 10.1016/s1734-1140(10)70387-x.

Abstract

The aim of this study was to determine and compare the anticonvulsant activities of four natural furanocoumarins [bergapten (5-methoxypsoralen), imperatorin (8-isopentenyloxypsoralen), oxypeucedanin (5-epoxy-isopentenyloxypsoralen) and xanthotoxin (8-methoxypsoralen)] in the maximal electroshock-induced seizure test in mice. The anticonvulsant effects of bergapten, imperatorin, oxypeucedanin, and xanthotoxin were evaluated at 15, 30, 60 and 120 min after their systemic (intraperitoneal) administration. Tonic hind limb extension (seizure activity) was evoked in adult albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. The time courses of protection by bergapten, imperatorin, oxypeucedanin and xanthotoxin against maximal electroshock-induced seizures revealed that 300 mg/kg imperatorin and xanthotoxin (C-8 substituted derivatives of psoralen) exerted strong anticonvulsant activity, whereas 300 mg/kg bergapten and oxypeucedanin (C-5 substituted derivatives of psoralen) did not produce any anticonvulsant activity in this model. In conclusion, imperatorin and xanthotoxin protected the animals against maximal electroshock-induced seizures, whereas bergapten and oxypeucedanin, despite their chemical and structural similarities to xanthotoxin and imperatorin, exerted no anticonvulsant activity in this seizure test.

摘要

本研究旨在确定并比较四种天然呋喃香豆素(补骨脂素(5-甲氧基补骨脂素)、异戊烯氧基补骨脂素(8-异戊烯氧基补骨脂素)、氧化补骨脂素(5-环氧异戊烯氧基补骨脂素)和花椒毒素(8-甲氧基补骨脂素))在最大电休克致惊厥试验中抗惊厥活性。在全身(腹腔内)给药后 15、30、60 和 120 分钟评估补骨脂素、异戊烯氧基补骨脂素、氧化补骨脂素和花椒毒素的抗惊厥作用。通过耳电极施加正弦波(25 mA、500 V、50 Hz、0.2 s 刺激持续时间)电流,诱发成年白化瑞士小鼠强直性后肢伸展(惊厥活动)。补骨脂素、异戊烯氧基补骨脂素、氧化补骨脂素和花椒毒素对最大电休克致惊厥的保护时间过程表明,300mg/kg 异戊烯氧基补骨脂素和花椒毒素(补骨脂素的 C-8 取代衍生物)具有很强的抗惊厥活性,而 300mg/kg 补骨脂素和氧化补骨脂素(补骨脂素的 C-5 取代衍生物)在该模型中没有产生任何抗惊厥活性。总之,异戊烯氧基补骨脂素和花椒毒素保护动物免受最大电休克引起的惊厥,而补骨脂素和氧化补骨脂素,尽管它们在化学和结构上与花椒毒素和异戊烯氧基补骨脂素相似,但在该惊厥试验中没有表现出抗惊厥活性。

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