Hosseinzadeh H, Sadeghnia H R
Faculty of Pharmacy, Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.
Phytomedicine. 2007 Apr;14(4):256-62. doi: 10.1016/j.phymed.2006.03.007. Epub 2006 May 16.
The aim of the present study was to evaluate the effects of safranal, an active constituent of Crocus sativus L. stigmas, on seizures induced by pentylenetetrazol. Intracerebroventricular (i.c.v.) microinjection of safranal (4.84, 9.68 and 24.2 micromol) had no effects on tonic and clonic phases as well as mortality upon seizures induced by PTZ (90mg/kg body wt., i.p.). Peripheral administration of safranal (72.75, 145.5 and 291 mg/kg body wt., i.p.), however, induced a dose-dependent decrease in the incidence of both minimal clonic seizures (MCS) (145.5 mg/kg body wt., p<0.01) and generalized tonic-clonic seizures (GTCS) (145.5 mg/kg body wt., p<0.001) following PTZ administration. Safranal also increased MCS and GTCS latency, significantly. Percent of protection against GTCS was 30%, 100% and 100% and mortality protection percent was 40%, 100% and 100% for the mentioned doses, respectively. Pretreatment with flumazenil (5 nmol, i.c.v.) and naloxone (5.5 nmol, i.c.v. and 2 mg/kg body wt., i.p.), 15 min prior to safranal administration (145.5 mg/kg body wt., i.p.), abolished the protective effect of safranal on MCS. Flumazenil also decreased the effect of safranal on incidence as well as latency of GTCS, significantly. These effects were not, however, significant for naloxone (5.5 nmol, i.c.v. and 2mg/kg body wt., i.p.). Results of this study demonstrated that safranal could exert anticonvulsant activity in the PTZ model and this effect may be mediated, at least partly, through GABA(A)-benzodiazepine receptor complex.
本研究的目的是评估藏红花柱头的活性成分藏红花醛对戊四氮诱导的癫痫发作的影响。脑室内（i.c.v.）微量注射藏红花醛（4.84、9.68和24.2微摩尔）对戊四氮（90毫克/千克体重，腹腔注射）诱导的癫痫发作的强直期、阵挛期以及死亡率均无影响。然而，腹腔注射藏红花醛（72.75、145.5和291毫克/千克体重）可导致戊四氮给药后最小阵挛性发作（MCS）（145.5毫克/千克体重，p<0.01）和全身性强直-阵挛性发作（GTCS）（145.5毫克/千克体重，p<0.001）的发生率呈剂量依赖性降低。藏红花醛还显著延长了MCS和GTCS的潜伏期。上述剂量对GTCS的保护率分别为30%、100%和100%，对死亡率的保护率分别为40%、100%和100%。在腹腔注射藏红花醛（145.5毫克/千克体重）前15分钟，脑室内注射氟马西尼（5纳摩尔）和纳洛酮（5.5纳摩尔，脑室内注射和2毫克/千克体重，腹腔注射）预处理可消除藏红花醛对MCS的保护作用。氟马西尼还显著降低了藏红花醛对GTCS的发生率和潜伏期的影响。然而，对于纳洛酮（5.5纳摩尔，脑室内注射和2毫克/千克体重，腹腔注射），这些影响并不显著。本研究结果表明，藏红花醛在戊四氮模型中可发挥抗惊厥活性，且这种作用可能至少部分通过GABA(A)-苯二氮䓬受体复合物介导。
