Ghias Mehreen, Shoaib Mohammad, Ali Shah Syed Wadood, Umar Muhammad Naveed, Ullah Shakir, Ali Niaz, Shah Ismail, Ullah Shafi
Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa, Pakistan.
Department of Chemistry, University of Malakand, Khyber Pakhtunkhwa, Pakistan.
Pak J Pharm Sci. 2019 Sep;32(5(Supplementary)):2325-2332.
The synthesized flavonoid derivatives (flavonols and flavones) were subjected for in-vitro anticholinesterase evaluation followed by assessment of in-vivo memory enhancing effects using animal models. The ex-vivo analysis of brain was carried out and portions were subjected foe estimation of biochemical parameters that includes AChE, ACh, SOD and CAT level. Among tested flavonoids, the para substituted chloro containing flavonol (OF2) and flavone (F2) revealed a considerable in-vitro AChE and BuChE % inhibition with an IC values. It was observed from the in-vivo results that OF1-OF3 at 12.5 mg/kg b.w has significance over F1-F3 in ameliorating the memory in scopolamine induced amnesic mice in passive avoidance step through and novel object recognitions test. Scopolamine elevated significantly the AChE level, decreased the contents of ACh, SOD and CAT in the brain in amnesic model. The flavonoid derivatives showed significant effects on these changes by decreasing the ex-vivo AChE contents, enhancing the level of ACh, SOD and CAT suggesting their possible role as cholinesterase and antioxidant. These findings suggest that synthetic flavonols and flavones may serve as potential candidates for developing safer and effective nootropic agents.
对合成的黄酮类衍生物（黄酮醇和黄酮）进行体外抗胆碱酯酶评估，随后使用动物模型评估其体内记忆增强作用。对大脑进行离体分析，并对部分样本进行生化参数估计，这些参数包括乙酰胆碱酯酶（AChE）、乙酰胆碱（ACh）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平。在测试的黄酮类化合物中，对位取代含氯的黄酮醇（OF2）和黄酮（F2）在体外对AChE和丁酰胆碱酯酶（BuChE）有相当程度的抑制作用，且有IC值。从体内结果观察到，在东莨菪碱诱导的被动回避和新物体识别试验的记忆障碍小鼠中，12.5mg/kg体重的OF1 - OF3在改善记忆方面比F1 - F3更具显著性。在记忆障碍模型中，东莨菪碱显著提高了大脑中AChE水平，降低了ACh、SOD和CAT的含量。黄酮类衍生物通过降低离体AChE含量、提高ACh、SOD和CAT水平，对这些变化显示出显著影响，表明它们可能作为胆碱酯酶和抗氧化剂发挥作用。这些发现表明，合成黄酮醇和黄酮可能成为开发更安全有效的益智药物的潜在候选物。
