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阿魏和欧洲接骨木及其潜在活性分离物在糖尿病性神经病理性疼痛小鼠模型中的急性和亚慢性体内效应。

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.

作者信息

Raafat K, El-Lakany A

机构信息

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Beirut Arab University (BAU), 115020, Beirut, Lebanon.

出版信息

BMC Complement Altern Med. 2015 Jul 30;15:257. doi: 10.1186/s12906-015-0780-7.

DOI:10.1186/s12906-015-0780-7
PMID:26220172
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4518631/
Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

糖尿病(DM)在全球范围内的患病率正在迅速上升,并伴有微血管和大血管并发症。糖尿病神经病变(DN)是DM的常见并发症,目前仅有少数几种获批疗法,疗效有限且有多种副作用。草药在全球范围内被用作一种有效的替代药物。本研究旨在研究赫莫阿魏(Ferula hermonis Boiss.)乙酸乙酯提取物(阿魏)和黑接骨木(Sambucus nigra L.)水提取物(接骨木)及其潜在活性分离物;在四氧嘧啶诱导的糖尿病小鼠模型中,对急性(6小时)和亚慢性(8天)血糖稳态、体内抗氧化潜力以及DN改善情况的影响。

方法

通过每48小时注射一次新鲜制备的四氧嘧啶,剂量为180 mg/kg,共注射三次,实验性诱导糖尿病。利用甩尾、热板潜伏期(评估热痛觉过敏)和von Frey细丝试验(评估触觉异常性疼痛),对DN进行较长时间(8周)的评估。

结果

通过生物导向分级分离和反相高效液相色谱浸泡法,从阿魏中分离出的最具活性的分离物是阿魏宁,从接骨木中分离出的是山奈酚。与作为阳性对照的格列本脲(GB)和曲马多(TRA)相比,测试化合物的最高剂量表现出显著的降血糖和抗伤害感受活性。阿魏宁观察到最佳的急性降血糖效果(比GB有效1.4倍)。接骨木表现出最佳的亚慢性降血糖效果(比GB有效2.6倍),并且在单次给药后对触觉异常性疼痛的疗效最佳,但改善热痛觉过敏需要重复给药。

结论

阿魏、接骨木及其活性分离物在改善糖尿病和长期糖尿病引起的并发症方面显示出显著效果,且没有现有疗法的使用限制副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/8e7780952c15/12906_2015_780_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/9319c6b3a47d/12906_2015_780_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/0a9b8e0e400c/12906_2015_780_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/47a6bb99fbd4/12906_2015_780_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/56e92df8a088/12906_2015_780_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/01705df06b26/12906_2015_780_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/8e7780952c15/12906_2015_780_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/9319c6b3a47d/12906_2015_780_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/0a9b8e0e400c/12906_2015_780_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/47a6bb99fbd4/12906_2015_780_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/56e92df8a088/12906_2015_780_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/01705df06b26/12906_2015_780_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e99/4518631/8e7780952c15/12906_2015_780_Fig6_HTML.jpg

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