Dhayabaran Daniel, Florance Ebinezar Jeyaseeli, Nandakumar Krishnadas, Shanmugarathinam Alagarsamy, Puratchikody Ayarivan
J Nat Med. 2014 Apr;68(2):310-5. doi: 10.1007/s11418-013-0798-4.
The heartwood of Cedrus deodara is traditionally used for the treatment of neurological disorders in India. In this study, the compound 3,4-bis(3,4-dimethoxyphenyl) furan-2,5-dione (BDFD) isolated from the ethanolic extract of C. deodara was evaluated for its anticonvulsant activity. The experimental studies were carried out in albino mice (18–22 g) and rats (180–220 g), employing different models of convulsions. The N-methyl-D-aspartic acid (NMDA)-induced lethality test and estimation of brain gamma-aminobutyric acid (GABA) were carried out to investigate the mechanism of action of this compound. BDFD gave dose-dependent protection against pentylenetetrazole (PTZ)-, pilocarpine- and 6-Hz-induced convulsions but it could not inhibit NMDA-induced lethality. Motor incoordination was displayed when the BDFD dose exceeded 400 mg/kg, whereas the therapeutic dose was below 100 mg/kg in the PTZ, pilocarpine and 6-Hz models (39–90 mg/kg). Furthermore, brain GABA estimation revealed that this compound increases the GABA level. BDFD dose levels up to 150 mg/kg did not prevent NMDA-induced lethality, which proves its weak influence on the excitatory neurotransmitter glutamate. The findings of the experiments on various animal models clearly demonstrated that BDFD possesses anticonvulsant activity by enhancing inhibitory GABAminergic neurotransmission.
在印度,喜马拉雅雪松的心材传统上用于治疗神经系统疾病。在本研究中,对从喜马拉雅雪松乙醇提取物中分离出的化合物3,4-双(3,4-二甲氧基苯基)呋喃-2,5-二酮(BDFD)的抗惊厥活性进行了评估。实验研究在白化小鼠(18 - 22克)和大鼠(180 - 220克)身上进行,采用了不同的惊厥模型。进行了N-甲基-D-天冬氨酸(NMDA)诱导的致死性试验以及脑γ-氨基丁酸(GABA)的测定,以研究该化合物的作用机制。BDFD对戊四氮(PTZ)、毛果芸香碱和6赫兹诱导的惊厥具有剂量依赖性保护作用,但不能抑制NMDA诱导的致死性。当BDFD剂量超过400毫克/千克时会出现运动不协调,而在PTZ、毛果芸香碱和6赫兹模型中治疗剂量低于100毫克/千克(39 - 90毫克/千克)。此外,脑GABA测定显示该化合物可提高GABA水平。高达150毫克/千克的BDFD剂量水平不能预防NMDA诱导的致死性,这证明其对兴奋性神经递质谷氨酸的影响较弱。在各种动物模型上的实验结果清楚地表明,BDFD通过增强抑制性GABA能神经传递而具有抗惊厥活性。