Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.
Psychopharmacology (Berl). 2021 Jul;238(7):1991-2009. doi: 10.1007/s00213-021-05826-7. Epub 2021 Mar 27.
Intracerebroventricular (ICV) streptozotocin (STZ) mimics sporadic Alzheimer's disease (SAD) characterized by tau pathology and neurodegeneration arising from oxidative stress, mitochondrial dysfunction, and insulin resistance. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid having antioxidant property interlinked with mitochondrial functioning and insulin actions.
To evaluate the neuroprotective and cognitive enhancement properties of 7,8-DHF in an ICV-STZ rat model of SAD.
ICV-STZ (3 mg/kg) was injected into male Wistar rats. Cognitive functions were evaluated by Morris water maze (MWM) and novel object recognition (NOR). 7,8-DHF (5 mg/kg, 10 mg/kg, and 20 mg/kg) and rivastigmine (2 mg/kg) were given orally for 21 days. Reduced glutathione (GSH), catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX), lipid peroxidation (LPO), protein carbonylation (PCO), and nitrite assays were performed. Mitochondrial enzyme complex I, II, III, and IV, and acetylcholinesterase (AchE) activities were determined. ELISA for the insulin-degrading enzyme (IDE) and p-tau was done. Histopathology was investigated by hematoxylin and eosin staining.
7,8-DHF treatment attenuated ICV-STZ-induced cognitive deficit in MWM and NOR. Moreover, in the cortex and hippocampus regions of the brain, GSH, catalase, SOD, GPX, LPO, PCO, and nitrite levels were reversed. Mitochondrial enzyme complex I, II, III, and IV, and acetylcholinesterase (AchE) activities were also normalized. IDE and p-tau protein were found to be significantly altered. 7,8-DHF provided protection from neuronal cell death examined in histopathology.
Conclusively, 7,8-DHF was found to be neuroprotective in the ICV-STZ rat model by ameliorating oxidative stress, mitochondrial dysfunction, and insulin resistance, thereby improving cognitive functions evident with the behavioral results.
脑室内（ICV）链脲佐菌素（STZ）模拟散发性阿尔茨海默病（SAD），其特征是tau 病理学和神经退行性变，由氧化应激、线粒体功能障碍和胰岛素抵抗引起。7,8-二羟基黄酮（7,8-DHF）是一种具有抗氧化特性的黄酮类化合物，与线粒体功能和胰岛素作用相关联。
评估 7,8-DHF 在 SAD 的 ICV-STZ 大鼠模型中的神经保护和认知增强特性。
雄性 Wistar 大鼠脑室内注射 STZ（3mg/kg）。通过 Morris 水迷宫（MWM）和新物体识别（NOR）评估认知功能。7,8-DHF（5mg/kg、10mg/kg 和 20mg/kg）和利伐斯的明（2mg/kg）经口给予 21 天。测定还原型谷胱甘肽（GSH）、过氧化氢酶、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPX）、脂质过氧化（LPO）、蛋白羰基化（PCO）和亚硝酸盐测定。测定线粒体酶复合物 I、II、III 和 IV 以及乙酰胆碱酯酶（AchE）活性。通过 ELISA 测定胰岛素降解酶（IDE）和 p-tau。通过苏木精和伊红染色进行组织病理学检查。
7,8-DHF 治疗可减轻 ICV-STZ 诱导的 MWM 和 NOR 认知障碍。此外，在大脑皮层和海马区，GSH、过氧化氢酶、SOD、GPX、LPO、PCO 和亚硝酸盐水平得到逆转。线粒体酶复合物 I、II、III 和 IV 以及乙酰胆碱酯酶（AchE）活性也得到了正常化。IDE 和 p-tau 蛋白也发生了显著改变。组织病理学检查发现，7,8-DHF 可提供神经元细胞死亡保护。
总之，7,8-DHF 通过改善氧化应激、线粒体功能障碍和胰岛素抵抗，在 ICV-STZ 大鼠模型中具有神经保护作用，从而改善认知功能，这与行为结果一致。
