Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
BMC Complement Med Ther. 2022 Nov 8;22(1):288. doi: 10.1186/s12906-022-03765-0.
Recent investigations suggested that anticancer agents may inhibit the progression of Alzheimer's disease (AD) pathology. Conyza dioscoridis (L.) was demonstrated to have anticancer, antioxidant, anti-inflammatory and antidiabetic effects. This study was carried out to investigate the efficacy of polyphenols from Conyza dioscoridis (L.) extract (PCDE) on AD.
Impacts of 3 doses of PCDE and donepezil, a reference drug, on the features of Alzheimer's disease in two animal models were investigated.
PCDE ameliorated the memory and learning impairment shown in rats following a single dose of scopolamine (scopolamine model) or 17 weeks of high-fat/high-fructose(HF/Hfr) diet coupled with a single dose of streptozotocin, (25 mg/kg) (T2D model). They reduced significantly the high hippocampal cholinesterase activity in the two models of rats. Administration of PCDE for 8 weeks in the T2D model showed a significant reduction in hippocampal GSK-3β, caspase-3 activity and increase in the inhibited glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). A significant reduction of HOMA-insulin resistance and serum hypercholesterolemia was observed. The Tau hyperphosphorylation and Aβ 1-42 generation in the hippocampal of T2D rats were significantly decreased by PCDE. Modulation of the oxidative stress markers, (rise in GH and SOD; decrease in MDA levels) and a significant reduction of TNF-α and IL-1β in the hippocampus of T2D rats treated by PCDE extract were important findings in this study. The highest dose tested was 4% of the highest safe dose.
Our study suggests that PCDE is multi-targeting agent with multiple beneficial activities in combating features of AD. This study may provide a novel therapeutic strategy for AD treatment that warrants clinical studies.
最近的研究表明，抗癌药物可能抑制阿尔茨海默病（AD）病理的进展。鬼针草（L.）已被证明具有抗癌、抗氧化、抗炎和抗糖尿病作用。本研究旨在探讨鬼针草（L.）提取物中的多酚（PCDE）对 AD 的疗效。
研究了 3 种剂量的 PCDE 和多奈哌齐（一种参考药物）对两种动物模型中 AD 特征的影响。
PCDE 改善了单次腹腔注射东莨菪碱（东莨菪碱模型）或 17 周高脂/高果糖（HF/Hfr）饮食联合单次链脲佐菌素（25mg/kg）（T2D 模型）后大鼠的记忆和学习障碍。它们显著降低了两种大鼠模型中海马胆碱酯酶活性的升高。在 T2D 模型中，PCDE 给药 8 周可显著降低海马 GSK-3β、caspase-3 活性，并增加抑制性谷氨酸受体表达（AMPA GluR1 亚基和 NMDA 受体亚基 NR1、NR2A、NR2B）。观察到胰岛素抵抗和血清高胆固醇血症显著降低。T2D 大鼠海马 Tau 过度磷酸化和 Aβ 1-42 生成明显减少。PCDE 显著调节氧化应激标志物（GH 和 SOD 升高；MDA 水平降低）和 T2D 大鼠海马 TNF-α和 IL-1β减少。测试的最高剂量是最高安全剂量的 4%。
我们的研究表明，PCDE 是一种多靶点药物，具有多种有益的活性，可对抗 AD 的特征。本研究为 AD 治疗提供了一种新的治疗策略，值得临床研究。
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