Macroautophagy, a sole pathway for dysfunctional organelles or aggregated proteins turnover, has been implicated in the early development of Alzheimer’s disease (AD). Previous studies have found that reversal of autophagy dysfunction in APP transgenic mice ameliorates amyloid pathologies. Icariin (ICA), the main component from traditional Chinese herb Epimedium brevicornu Maxim., can reduce accumulations of amyloid-β (Aβ) peptide in vivo and in vitro, but the mechanism remains unclear. Here, we explored the effects of ICA on autophagy-lysosomal pathway in intracerebroventricular (icv) injection of human Aβ_1–42 peptide rats. We demonstrated that feeding the rats with ICA (30 mg/kg, 60 mg/kg and 90 mg/kg rat, per os) for 4 weeks rescued the Aβ_1–42-induced spatial memory impairments, reduced endogenous rat Aβ₄₂ tested by ELISA and decreased Aβ accumulation using 6E10 antibody. Furthermore, Aβ_1–42 induced strong autophagy response, however ICA decreased the levels of microtubule-associated protein 1 light chain 3 (LC3) II/LC3I, Beclin1, Cathepsin D (Cat D) and brain lysosomal Cathepsin D activity. We also observed that ICA enhanced the phosphorylation of protein kinase B (PKB/AKT) and p70 ribosomal protein S6 kinase (p70S6K). In addition, ICA arrested Aβ_1–42-induced cells loss, mitochondrias damage, nuclear membranes unclear and abundant nucleas chromatin agglutinates in hippocampus, lessened the expression of Cleaved-caspase-3, brain oxidative stress, astroglial activation. These findings suggest that ICA can ameliorate amyloid pathologies with improving autophagy-lysosome function and Chinese materia medica may be potential for AD treatment.

巨噬细胞吞噬是细胞器功能失调或蛋白质聚集失调的唯一途径，它与阿尔茨海默氏病（AD）的早期发展有关。先前的研究发现，APP转基因小鼠中自噬功能的逆转改善了淀粉样蛋白的病状。Icariin（ICA）是中草药淫羊Epi（Epimedium brevicornu Maxim ）的主要成分，在体内和体外均可减少淀粉样β（Aβ）肽的积累，但机理尚不清楚。在这里，我们探讨了ICA对脑室内（icv）注射人_Aβ1–42肽大鼠的自噬溶酶体途径的影响。我们证明用ICA（30 mg / kg，60 mg / kg和90 mg / kg大鼠，每个os）喂养大鼠4周可以挽救_Aβ1–42诱导的空间记忆障碍，通过ELISA检测的内源性大鼠_Aβ42减少和使用6E10抗体的Aβ积累减少 此外，_Aβ1–42诱导了强烈的自噬反应，但是ICA降低了微管相关蛋白1轻链3（LC3）II / LC3I，Beclin1，组织蛋白酶D（Cat D）和脑溶酶体组织蛋白酶D的水平。我们还观察到ICA增强了蛋白激酶B（PKB / AKT）和p70核糖体蛋白S6激酶（p70S6K）的磷酸化。此外，ICA逮捕了_Aβ1–42诱导的海马细胞丢失，线粒体损伤，核膜不清楚和核染色质凝集物丰富，减少了Cleaved-caspase-3的表达，脑部氧化应激，星形胶质细胞活化。这些发现表明，ICA可以改善淀粉样蛋白的病状，改善自噬溶酶体的功能，而中药可能具有AD治疗的潜力。