PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, 71491, Saudi Arabia.
Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt.
Curr Alzheimer Res. 2024;21(4):276-288. doi: 10.2174/0115672050333388240801043509.
Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.
We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.
阿尔茨海默病(AD)影响全球约 5000 万人,预计到 2050 年将增加两倍。牛蒡子苷是牛蒡属植物中的一种木脂素。牛蒡子苷具有抗增殖、抗氧化和抗脂肪生成作用。
通过评估 TLR4、NLRP3、STAT3、TGF-β、cyclin D1 和 CDK2 的表达,探讨牛蒡子苷对 AD 大鼠的潜在治疗作用。
通过腹腔注射每天 70mg/kg 的氯化铝,6 周诱导 AD。AD 诱导后,部分大鼠通过灌胃每天给予 25mg/kg 的牛蒡子苷治疗 3 周。此外,为了检查脑组织结构,用苏木精/伊红和抗 TLR4 抗体对海马切片进行染色。分析收集的样品中 TLR4、NLRP3、STAT3、TGF-β、cyclin D1 和 CDK2 的基因表达和蛋白水平。
在行为测试中,牛蒡子苷治疗的大鼠行为有显著改善。苏木精/伊红染色的微图像显示,牛蒡子苷有助于改善海马结构的完整性和凝聚力,AD 先前已损害了这些结构。此外,牛蒡子苷降低了 TLR4、NLRP3、STAT3、TGF-β、cyclin D1 和 CDK2 的表达。
牛蒡子苷可增强 AD 大鼠的行为和海马结构。这是通过降低 TLR4 和 NLRP3 的表达来实现的,从而抑制了炎症小体途径。此外,牛蒡子苷通过调节 STAT3 和 TGF-β 可改善组织纤维化。最后,它可以阻断细胞周期蛋白 cyclin D1 和 CDK2。