Khan Shahab Ali, Haider Ali, Mahmood Wajahat, Roome Talat, Abbas Ghulam
a Department of Pharmacy , COMSATS Institute of Information Technology , Abbottabad , K.P.K. , Pakistan.
b Department of Pathology, Dow International Medical College , Dow University of Health Sciences , Karachi , Pakistan.
Pharm Biol. 2017 Dec;55(1):1817-1823. doi: 10.1080/13880209.2017.1331363.
γ-Linolenic acid (GLA) is an important constituent of anti-ageing supplements.
The current study investigates the anti-ageing effect of GLA in Sprague-Dawley rats.
GLA (0.1, 0.2, 0.4, 2, 10, 20 and 24 μM) was initially evaluated for its effect on the formation of advanced glycation end products (AGEs) in vitro. For in vivo assessment (1, 5 or 15 mg/kg), the rat model of accelerated ageing was developed using d-fructose (1000 mg/kg (i.p.) plus 10% in drinking water for 40 days). Morris water maze was used to evaluate impairment in learning and memory. The blood of treated animals was used to measure glycosylated haemoglobin (HbA1c) levels. The interaction of GLA with active residues of receptor of AGE (RAGE) was analyzed using AutoDock Vina.
Our data showed that GLA inhibited the production of AGEs (IC = 1.12 ± 0.05 μM). However, this effect was more significant at lower tested doses. A similar pattern was also observed in in vivo experiments, where the effect of fructose was reversed by GLA only at lowest tested dose of 1 mg/kg. The HbA1c levels also revealed significant reduction at lower doses (1 and 5 mg/kg). The in silico data exhibited promising interaction of GLA with active residues (Try72, Arg77 and Gln67) of RAGE.
The GLA, at lower doses, possesses therapeutic potential against glycation-induced memory decline.
γ-亚麻酸（GLA）是抗衰老补充剂的重要成分。
本研究调查GLA对斯普拉格-道利大鼠的抗衰老作用。
首先评估GLA（0.1、0.2、0.4、2、10、20和24μM）对体外晚期糖基化终产物（AGEs）形成的影响。对于体内评估（1、5或15mg/kg），使用d-果糖（1000mg/kg（腹腔注射）加饮用水中10%，持续40天）建立加速衰老大鼠模型。采用莫里斯水迷宫评估学习和记忆障碍。用处理过的动物血液测量糖化血红蛋白（HbA1c）水平。使用AutoDock Vina分析GLA与AGE受体（RAGE）活性残基的相互作用。
我们的数据表明，GLA抑制AGEs的产生（IC = 1.12±0.05μM）。然而，在较低测试剂量下这种作用更显著。在体内实验中也观察到类似模式，仅在最低测试剂量1mg/kg时，GLA才逆转了果糖的作用。较低剂量（1和5mg/kg）时HbA1c水平也显著降低。计算机模拟数据显示GLA与RAGE的活性残基（Try72、Arg77和Gln67）有良好的相互作用。
较低剂量的GLA具有对抗糖基化诱导的记忆衰退的治疗潜力。
