Shoja Maryam, Mehri Soghra, Amin Bahareh, Askari Vahid Reza, Hosseinzadeh Hossein
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
J Pharmacopuncture. 2018 Dec;21(4):277-283. doi: 10.3831/KPI.2018.21.031. Epub 2018 Dec 31.
Ethanol withdrawal following its chronic use is a serious outcome and challenging to treatment. The chronic use of ethanol induces a progressive neuroplasticity in different reigns of brain. In this study we evaluated the effects of aqueous extract of L. (saffron) and its active compound, crocin, on the withdrawal behavior induced after repeated administration of ethanol, in two regimens of prophylactic (administration of drugs concomitant with the induction of dependence) and treatment (administration of drugs during the period of ethanol withdrawal) in mice which received ethanol.
Ethanol dependence was induced by oral administration of 10% v/v ethanol (2 g/kg) for 7 days. The aqueous extracts of saffron (40, 80 and 160) and crocin (10, 20 and 40 mg/kg) were administered to mice in two regimens of prophylactic (along with ethanol) and treatment (during withdrawal period). Diazepam (1 mg/kg) was used as a positive control. Six hours after discontinuation of the ethanol, seizure was evaluated by the sub-convulsive dose of pentyleneltetrazole (PTZ) (30 mg/kg). The open field test and Rota rod test were used for evaluation of locomotor activity and motor incoordination, respectively.
Both extracts and crocin increased the number of crossed lined in the open field test. PTZ kindling seizure was inhibited in animals received extract (80 and 160 mg/kg) in both regimens. Motor incoordination was only improved following administration of crocin.
The aqueous extract of saffron and crocin can be considered as safe agents and reliable alternative to diazepam in management of ethanol withdrawal syndrome.
长期使用乙醇后戒断是一个严重后果且治疗具有挑战性。长期使用乙醇会在大脑的不同区域诱导渐进性神经可塑性。在本研究中,我们评估了藏红花水提取物及其活性化合物西红花苷对乙醇反复给药后诱导的戒断行为的影响,在接受乙醇的小鼠中采用两种方案,即预防性(与诱导依赖性同时给药)和治疗性(在乙醇戒断期间给药)。
通过口服10% v/v乙醇(2 g/kg)持续7天诱导乙醇依赖性。将藏红花水提取物(40、80和160)和西红花苷(10、20和40 mg/kg)以预防性(与乙醇一起)和治疗性(在戒断期)两种方案给予小鼠。地西泮(1 mg/kg)用作阳性对照。乙醇停用6小时后,通过亚惊厥剂量的戊四氮(PTZ)(30 mg/kg)评估惊厥。旷场试验和转棒试验分别用于评估运动活动和运动不协调。
提取物和西红花苷均增加了旷场试验中穿过的格子数。在两种方案中,接受提取物(80和160 mg/kg)的动物中PTZ点燃惊厥均受到抑制。仅在给予西红花苷后运动不协调得到改善。
藏红花水提取物和西红花苷可被视为安全药物,是地西泮治疗乙醇戒断综合征的可靠替代药物。