Acute and subchronic in-vivo effects of Ferula hermonis L. and Sambucus nigra L. and their potential active isolates in a diabetic mouse model of neuropathic pain.

Acute and subchronic in-vivo effects of Ferula hermonis L. and Sambucus nigra L. and their potential active isolates in a diabetic mouse model of neuropathic pain.
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DOI:
10.1186/s12906-015-0780-7
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发表时间:
2015-07-30
影响因子:
--
通讯作者:
El-Lakany A
El-Lakany A
中科院分区:
医学3区
文献类型:
--
作者:
Raafat K;El-Lakany A

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糖尿病(Diabetes mellitus,DM)的患病率在全球范围内迅速上升,并伴有微血管和大血管并发症.糖尿病神经病变(DN)是糖尿病常见的并发症,目前已被批准的治疗方法很少,但疗效有限,副作用多。草药在世界范围内被用作一种有效的替代医学。研究了阿魏的药理活性。乙酸乙酯(阿魏)和接骨木。水(Elder)提取物及其潜在活性分离物;用于急性(6小时)和亚慢性(8天)葡萄糖稳态、体内抗氧化潜力和四氧嘧啶诱导的DM小鼠模型中的DN改善。通过以180 mg/kg的剂量每48 h注射新鲜制备的四氧嘧啶三次来实验性诱导DM。采用甩尾、热板刺激(热痛觉过敏)和von Frey细丝测试(触觉异常性疼痛),对DN进行较长时间(8周)的评估。利用生物导向分离和RP-HPLC浸渍方法,从阿魏中分离出的活性最高的分离物是阿魏素和从接骨木中分离出的山奈酚。与作为阳性对照的格列本脲(GB)和曲马多(TRA)相比,最高剂量的受试化合物具有显著的降血糖和抗伤害活性。观察到最佳的急性降血糖作用是使用ferutinin(比GB有效1.4倍)。Elder在单次给药后显示出最好的亚慢性降血糖作用(比GB有效2.6倍)和对触觉异常性疼痛的最大功效,但需要重复给药以改善热痛觉过敏。在没有现有疗法的使用限制性副作用的情况下,阿魏、接骨木及其活性分离物在改善DM和长期存在的糖尿病诱导的并发症方面显示出显著的结果。
The prevalence of Diabetes mellitus (DM) is escalating rapidly worldwide, and associated with micro- and macrovascular complications. Diabetic neuropathy (DN) is a common complication of DM, and has a few approved therapies with limited efficacy and several side-effects. Herbal medicine is used worldwide as an effective alternative-medicine. The present study aims to investigate the activities of Ferula hermonis Boiss. EtAc (Ferula) and Sambucus nigra L. aqueous (Elder) extracts, and their potential active isolates; for acute (6 h) and subchronic (8 days) glucose homeostasis, in vivo antioxidant potential and DN amelioration in alloxan-induced DM mice model. DM was induced experimentally by injection of freshly prepared alloxan every 48-h for three times at a dose of 180 mg/kg. Utilizing tail-flick, hot-plate latencies (accessing thermal hyperalgesia) and von Frey filaments test (accessing tactile allodynia), DN was evaluated for longer period of time (8 weeks). The most active isolates from Ferula was ferutinin, and Kaempferol from Elder utilizing bio-guided fractionation and RP-HPLC steeping methods. Compared to glibenclamide (GB) and tramadol (TRA), as positive controls, the highest doses of tested compounds exerted remarkable hypoglycemic and antinociceptive activities. The best acute hypoglycemic effect was observed with ferutinin (1.4 folds more effective than GB). Elder has shown the best subchronic hypoglycemic effect (2.6 folds more effective than GB) and the greatest efficacy against tactile allodynia following a single-administration, yet required repeated administration for improvement of thermal hyperalgesia. Without the use-limiting-side-effects of existing therapies, Ferula, Elder and their active isolates have shown significant results in ameliorating DM and long standing diabetes-induced complications.