Effect of Linguizhugan decoction on neuroinflammation and expression disorder of the amyloid β‑related transporters RAGE and LRP‑1 in a rat model of Alzheimer's disease

苓桂术甘汤对阿尔茨海默病大鼠神经炎症及淀粉样β蛋白相关转运体RAGE、LRP-1表达紊乱的影响

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作者:Qianfeng Hu, Beibei Yu, Qinlei Chen, Yi Wang, Yun Ling, Songxian Sun, Yinlong Shi, Chunxiang Zhou

Abstract

Linguizhugan decoction (LGZG), a notable prescription in Traditional Chinese Medicine, is a classical formula for the treatment of Alzheimer's disease (AD), inflammatory injury and fluid retention. The present study aimed to investigate the neuroprotective effect of LGZG on an amyloid β (Aβ)‑induced AD rat model. Sprague‑Dawley rats were administered with Aβ1‑42 to induce AD and inflammatory responses, and subsequently with LGZG (4.8, 2.4 or 1.2 g/kg), donepezil (2 mg/kg) or distilled water for 30 consecutive days. Learning and memory behaviors were evaluated via Morris water maze test. The neuronal impairment of AD rats was observed via hematoxylin‑eosin staining. The levels of pro‑inflammatory cytokines, and Aβ in the brain tissue were detected with ELISA kits. Protein expression levels of mitogen‑activated protein kinase and nuclear factor‑κB signalling were measured by western blot analysis. The expression of lipoprotein receptor‑related protein‑1 (LRP‑1) and receptor for advanced glycation endproducts (RAGE) in the brain were detected by western blot analysis, reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry analysis. LGZG was demonstrated to significantly improve learning and memory ability, and ameliorate neuroinflammation in AD rats. LGZG increased the levels of LRP‑1 and decreased the levels of RAGE. Furthermore, the present results demonstrated that LGZG treatment significantly inhibited MAPK and NF‑κB signalling, and reduced the production of pro‑inflammatory cytokines and Aβ accumulation in AD rats. LGZG exhibited a potential protective effect on Aβ1‑42‑induced AD by regulating Aβ transportation, and inhibiting RAGE/MAPK and NF‑κB signalling. These results suggest that LGZG may be considered for the treatment of AD.

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