Aminirad Alireza, Mousavi Seyyedeh Elaheh, Fakhraei Nahid, Mousavi Seyyedeh Mahbubeh, Rezayat Seyed Mahdi
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Neurosci Lett. 2017 Jun 9;651:226-231. doi: 10.1016/j.neulet.2017.05.018. Epub 2017 May 10.
A plant alkaloid obtained from Curcuma longa, curcumin possesses anti-oxidant and anti-inflammatory effects. Nanoformulations have been developed for preclinical studies which demonstrate enhanced therapeutic efficacy. Effect of acute intraperitoneal (i.p.) administration of curcumin C3 complex nanoparticles [1,5, 10, 20, 40, 80mg/kg, (i.p.)] 75min prior to PTZ, on clonic seizure thresholds induced by intravenous infusion of pentylenetetrazole (PTZ) 0.5% was investigated in comparison with curcumin (40 and 80mg/kg, i.p.) in male mice. Moreover, to clarify the probable role of NO in the anticonvulsant property of nanocurcumin, non-effective doses of l-arginine (l-Arg), a NO donor; 7-nitroindazole, 7-NI, a preferential neuronal NO synthase inhibitor; L-NAME, a non-selective NO synthase inhibitor and aminoguanidine (AG), a selective inducible NO synthase inhibitor (iNOS), in combination with nanocurcumin (80mg/kg, i.p.), 15-30min before it were employed.
While curcumin did not show any anticonvulsant effect, nanocurcumin revealed dose-dependent anticonvulsant property at the doses 20, 40 and 80mg/kg, P<0.01, P<0.01 and P<0.001, respectively. l-Arg (30 and 60mg/kg) dose-dependently reversed the anticonvulsant effect of the most effective nanocurcumin dose (80mg/kg), P<0.01 and P<0.001, respectively. On the other hand, L-NAME (3 and 10mg/kg, i.p.) markedly potentiated the sub effective dose of nanocurcumin (10mg/kg), P<0.01 and P<0.001, respectively. Similarly, AG (50 and 100mg/kg, i.p.) profoundly augmented the seizure thresholds of nanocurcumin (10mg/kg), P<0.01 and P<0.001, respectively. In addition, 7-NI (10, 30 and 60mg/kg, i.p.) failed to influence the responses.
These data may support excess of NO production following PTZ infusion probably resulting from iNOS source. Consequently, nanocurcumin probably down regulated NO. To conclude, nanocurcumin showed anticonvulsant effect. Furthermore, this effect was reversed following l-arginine as an external NO precursor. However, both the non-selective NOS inhibitor and selective iNOS inhibitor increased the thresholds. It is evident that nanocurcumin may influence the seizure thresholds at least in part through a decrease in NO.
姜黄素是从姜黄中提取的一种植物生物碱，具有抗氧化和抗炎作用。已开发出纳米制剂用于临床前研究，这些研究表明其治疗效果有所增强。在雄性小鼠中，研究了在腹腔注射戊四氮（PTZ）0.5%前75分钟腹腔注射姜黄素C3复合纳米颗粒[1、5、10、20、40、80mg/kg，（腹腔注射）]对静脉输注PTZ诱导的阵挛性惊厥阈值的影响，并与腹腔注射姜黄素（40和80mg/kg）进行比较。此外，为了阐明一氧化氮（NO）在纳米姜黄素抗惊厥特性中的可能作用，使用了无效剂量的NO供体L-精氨酸（L-Arg）；7-硝基吲唑（7-NI），一种选择性神经元型一氧化氮合酶抑制剂；L-硝基精氨酸甲酯（L-NAME），一种非选择性一氧化氮合酶抑制剂；以及氨基胍（AG），一种选择性诱导型一氧化氮合酶抑制剂（iNOS），在纳米姜黄素（80mg/kg，腹腔注射）前15 - 30分钟与纳米姜黄素联合使用。
虽然姜黄素未显示出任何抗惊厥作用，但纳米姜黄素在20、40和80mg/kg剂量下显示出剂量依赖性抗惊厥特性，P分别<0.01、<0.01和<0.001。L-Arg（30和60mg/kg）剂量依赖性地逆转了最有效纳米姜黄素剂量（80mg/kg）的抗惊厥作用，P分别<0.01和<0.001。另一方面，L-NAME（3和10mg/kg，腹腔注射）显著增强了纳米姜黄素的次有效剂量（10mg/kg），P分别<0.01和<0.001。同样，AG（5和10mg/kg，腹腔注射）显著提高了纳米姜黄素（10mg/kg）的惊厥阈值，P分别<0.01和<0.001。此外，7-NI（10、30和60mg/kg，腹腔注射）未能影响反应。
这些数据可能支持PTZ输注后可能由诱导型一氧化氮合酶来源导致的NO产生过量。因此，纳米姜黄素可能下调了NO。总之，纳米姜黄素显示出抗惊厥作用。此外，作为外源性NO前体的L-精氨酸可逆转这种作用。然而，非选择性一氧化氮合酶抑制剂和选择性诱导型一氧化氮合酶抑制剂均提高了惊厥阈值。很明显，纳米姜黄素可能至少部分通过降低NO来影响惊厥阈值。
