Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Chin J Physiol. 2023 Jul-Aug;66(4):209-219. doi: 10.4103/cjop.CJOP-D-23-00006.
Sericin (Ser) is a natural neuroactive macromolecule with diverse pharmacological properties, and our previous findings have shown its neuroprotective potentials. This study aimed to investigate the therapeutic potential of Ser on cognitive dysfunction induced by transient global cerebral ischemia/reperfusion (tGI/R) and its mechanism of action. The tGI/R was induced in BALB/c mice by bilateral occlusion of the common carotid arteries for two 5 min followed by a 10-min reperfusion period. After 24 h, mice were treated with normal saline or different doses of Ser (100, 200, and 300 mg/kg) for 10 days. Cognitive performances were assessed using the Barnes maze and social interaction tasks. Oxidative stress markers including superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) as well as pro-inflammatory cytokines (interleukin (IL)-6 and tumor necrosis factor-alpha) and anti-inflammatory cytokine (IL-10) were assessed in the hippocampus. Markers of apoptosis (pro- and cleaved caspase-9 and 3, Bax, and Bcl-2) were assessed by Western blotting. Besides, transferase-mediated dUTP nick end-labeling assay was used to detect apoptotic cell death. We show here that Ser administration improved tGI/R-induced cognitive deficits, enhanced the activity of SOD and GPx, increased TAC levels, while reduced MDA levels. Notably, Ser decreased neuronal apoptotic cell death in the hippocampal dentate gyrus (DG) region, accompanied by suppression of neuroinflammation, downregulation of pro-apoptotic proteins (caspase-9, caspases-3, and Bax), and upregulation of anti-apoptotic protein, Bcl-2. Taken together, Ser administration protected hippocampal neurons from apoptotic cell death by impeding oxidative stress and inflammatory responses and, in turn, improved cognitive function in the tGI/R mice.
丝胶（Ser）是一种具有多种药理学特性的天然神经活性大分子，我们之前的研究结果表明其具有神经保护潜力。本研究旨在探讨 Ser 对短暂性全脑缺血/再灌注（tGI/R）诱导的认知功能障碍的治疗潜力及其作用机制。通过双侧阻断颈总动脉 5 分钟，再进行 10 分钟再灌注，在 BALB/c 小鼠中诱导 tGI/R。24 小时后，小鼠用生理盐水或不同剂量的 Ser（100、200 和 300 mg/kg）治疗 10 天。使用 Barnes 迷宫和社交互动任务评估认知表现。在海马体中评估氧化应激标志物，包括超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、总抗氧化能力（TAC）和丙二醛（MDA）以及促炎细胞因子（白细胞介素（IL）-6 和肿瘤坏死因子-α）和抗炎细胞因子（IL-10）。通过 Western blot 评估凋亡标志物（pro 和 cleaved caspase-9 和 3、Bax 和 Bcl-2）。此外，使用转移酶介导的 dUTP 缺口末端标记法检测细胞凋亡。我们在这里表明，Ser 给药改善了 tGI/R 诱导的认知障碍，提高了 SOD 和 GPx 的活性，增加了 TAC 水平，同时降低了 MDA 水平。值得注意的是，Ser 减少了海马齿状回（DG）区神经元的凋亡细胞死亡，同时抑制了神经炎症，下调了促凋亡蛋白（caspase-9、caspases-3 和 Bax），并上调了抗凋亡蛋白 Bcl-2。总之，Ser 通过阻止氧化应激和炎症反应来保护海马神经元免受凋亡细胞死亡，并改善 tGI/R 小鼠的认知功能。
