Tao Xue, Zhang Rong, Wang Liguo, Li Xiaoling, Gong Weijun
Department of Research, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
The Second Clinical Medical College, Yunnan University of Chinese Medicine, Yunnan, China.
J Alzheimers Dis. 2023;92(1):195-208. doi: 10.3233/JAD-220904.
Alzheimer's disease (AD) disturbs many patients and family. However, little progress has been made in finding effective treatments. Given AD is a multifactorial disease, luteolin and exercise combination therapy may be more effective than monotherapy.
To explore the therapeutic effect and underlying mechanisms of luteolin and exercise combination therapy in AD treatment.
This study utilized a validated mouse model of AD by bilateral injection of amyloid-β (Aβ)1-42 oligomers into the CA1 region of the hippocampus. By combining with animal behavioral test, thioflavin T detection, immunofluorescence and western blot test, the cognitive-enhancing effects of luteolin and exercise combination therapy and the underlying mechanisms were investigated.
Luteolin (100 mg/kg/d) combined with exercise could significantly improve the performance of AD model mice in novel object recognition test, and the improvement was greater than that of monotherapy. Further experiments showed that luteolin and exercise alone or in combination could reverse the increase of Aβ content, the activation of astrocytes and microglia, and the decrease of the level of autophagy in hippocampus and cortex in AD model induced by Aβ1-42 oligomers. While the combination therapy involved more intact hippocampal and cortical areas, with greater degree of changes.
Luteolin and exercise combination therapy prevented Aβ1-42 oligomers-induced cognitive impairment, possibly by decreasing neuroinflammation and enhancing autophagy. The luteolin and exercise combination therapy may be a useful therapeutic option for preventing and/or delaying the progression of memory dysfunction of AD.
阿尔茨海默病（AD）困扰着许多患者及其家庭。然而，在寻找有效治疗方法方面进展甚微。鉴于AD是一种多因素疾病，木犀草素与运动联合疗法可能比单一疗法更有效。
探讨木犀草素与运动联合疗法在AD治疗中的疗效及潜在机制。
本研究通过向海马体CA1区双侧注射淀粉样β蛋白（Aβ）1-42寡聚体建立了经过验证的AD小鼠模型。通过结合动物行为测试、硫黄素T检测、免疫荧光和蛋白质印迹试验，研究木犀草素与运动联合疗法的认知增强作用及其潜在机制。
木犀草素（100mg/kg/d）与运动联合可显著提高AD模型小鼠在新物体识别测试中的表现，且改善程度大于单一疗法。进一步实验表明，单独或联合使用木犀草素和运动均可逆转Aβ1-42寡聚体诱导的AD模型中海马体和皮质中Aβ含量的增加、星形胶质细胞和小胶质细胞的激活以及自噬水平的降低。联合疗法涉及的海马体和皮质区域更完整，变化程度更大。
木犀草素与运动联合疗法可预防Aβ1-42寡聚体诱导的认知障碍，可能是通过减轻神经炎症和增强自噬实现的。木犀草素与运动联合疗法可能是预防和/或延缓AD记忆功能障碍进展的一种有效治疗选择。
