Zhong Junjie, Wang Zhifu, Xie Qiang, Li Tianwen, Chen Kezhu, Zhu Tongming, Tang Qisheng, Shen Chao, Zhu Jianhong
Fudan University Huashan Hospital, Dept. of Neurosurgery, State Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College-Fudan University. 12 Urumqi Zhong Road, Shanghai 200040, China.
Fudan University Huashan Hospital, Dept. of Neurosurgery, State Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College-Fudan University. 12 Urumqi Zhong Road, Shanghai 200040, China.
Int Immunopharmacol. 2020 Jun;83:106491. doi: 10.1016/j.intimp.2020.106491. Epub 2020 Apr 9.
Oxidative stress acts as the major causative factor for various age-associated neurodegenerative diseases, triggering cognitive and memory impairments. In the present study, the underlying neuroprotective mechanism governing how shikonin acts against D-galactose (D-gal)-induced memory impairment, neuroinflammation and neuron damage was examined. The results revealed that chronic administration of D-gal [150 mg/kg intraperitoneally (i.p.)] in mice caused cognitive and memory impairments, as determined by Morris water-maze test. Shikonin treatment, however, alleviated D-gal-induced memory impairment and reversed the D-gal-induced neural damage and apoptosis. Furthermore, western blotting and the results of morphological analysis revealed that shikonin treatments markedly reduced D-gal induced neuroinflammation through inhibition of astrocytosis as determined by glial fibrillary acidic protein (GFAP) detection, and downregulating other inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Moreover, shikonin treatment led to inhibition of the activation of nuclear factor-κB (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs), preventing neurodegeneration. Hence, taken together, the results of the present study suggested that shikonin attenuated D-gal-induced memory impairment, neuroinflammation and neurodegeneration, possibly via the NF-κB/mitogen-activated protein kinase (MAPK) pathway. Our data suggest that shikonin could be a promising, endogenous and compatible antioxidant candidate for age-associated neurodegenerative diseases, including Alzheimer's disease.
氧化应激是多种与年龄相关的神经退行性疾病的主要致病因素，可引发认知和记忆障碍。在本研究中，我们研究了紫草素针对D-半乳糖（D-gal）诱导的记忆障碍、神经炎症和神经元损伤的潜在神经保护机制。结果显示，通过莫里斯水迷宫试验测定，小鼠腹腔注射（i.p.）150 mg/kg D-半乳糖可导致认知和记忆障碍。然而，紫草素治疗可减轻D-半乳糖诱导的记忆障碍，并逆转D-半乳糖诱导的神经损伤和细胞凋亡。此外，蛋白质免疫印迹法和形态学分析结果显示，通过检测胶质纤维酸性蛋白（GFAP）确定，紫草素治疗可通过抑制星形胶质细胞增生显著减轻D-半乳糖诱导的神经炎症，并下调其他炎症介质，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和IL-6。此外，紫草素治疗可抑制核因子-κB（NF-κB）的激活和丝裂原活化蛋白激酶（MAPK）的磷酸化，从而预防神经退行性变。因此，本研究结果表明，紫草素可能通过NF-κB/丝裂原活化蛋白激酶（MAPK）途径减轻D-半乳糖诱导的记忆障碍、神经炎症和神经退行性变。我们的数据表明，紫草素可能是一种有前景的、内源性且兼容性良好的抗氧化剂，可用于治疗包括阿尔茨海默病在内的与年龄相关的神经退行性疾病。
