Tian Yue, Jing Guangchan, Yin Ruiying, Ma Mei, Cao Weiwei, Zhang Mengren
Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Beijing HFK Bioscience Co., LTD, Beijing 102200, China.
Brain Res. 2025 Feb 15;1849:149365. doi: 10.1016/j.brainres.2024.149365. Epub 2024 Nov 29.
The increasing prevalence of diabetes and its related cognitive impairments is a significant public health concern. With limited clinical treatment options and an incomplete understanding of the underlying mechanisms, traditional Chinese medicine (TCM) Naofucong is proposed as a potential neuroprotective agent against diabetic cognitive impairment (DCI). This study aims to investigate the therapeutic mechanisms of Naofucong in DCI. We hypothesize that Naofucong may improve cognitive function in diabetic rats by modulating the extracellular regulated protein kinases (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinases (MAPK) signaling pathway, enhancing insulin-degrading enzyme (IDE) expression, reducing amyloid-beta (Aβ) deposition, decreasing phosphorylated Tau (p-Tau) levels, and alleviating oxidative stress. Diabetes was induced in specific-pathogen-free male Sprague-Dawley rats using streptozotocin, and the rats were treated with oral Naofucong for 12 weeks. We assessed cognitive function and measured neuronal damage, oxidative stress injury, and the expression levels of IDE, Aβ, amyloid precursor protein (APP), p-Tau, and components of the ERK/JNK/p38 MAPK pathway. Diabetic rats showed significant declines in cognitive function, neuronal damage, oxidative stress, low IDE expression, Aβ accumulation, high APP expression, abnormal Tau phosphorylation, and overactivation of the ERK/JNK/p38 MAPK pathway. Naofucong treatment significantly reversed these symptoms. Our findings suggest that Naofucong improves cognitive impairment in diabetic rats by inhibiting the ERK/JNK/p38 MAPK pathway, upregulating IDE, reducing Aβ deposition, suppressing APP and p-Tau expression, and alleviating neuronal damage and oxidative stress. This research provides a reference for the clinical prevention and treatment of DCI using TCM Naofucong.
糖尿病及其相关认知障碍的患病率不断上升，这是一个重大的公共卫生问题。由于临床治疗选择有限且对潜在机制的了解不完整，中药脑复聪被提议作为一种针对糖尿病认知障碍（DCI）的潜在神经保护剂。本研究旨在探讨脑复聪治疗DCI的机制。我们假设脑复聪可能通过调节细胞外调节蛋白激酶（ERK）/c-Jun氨基末端激酶（JNK）/p38丝裂原活化蛋白激酶（MAPK）信号通路、增强胰岛素降解酶（IDE）表达、减少β淀粉样蛋白（Aβ）沉积、降低磷酸化Tau（p-Tau）水平以及减轻氧化应激来改善糖尿病大鼠的认知功能。使用链脲佐菌素在特定病原体-free雄性Sprague-Dawley大鼠中诱导糖尿病，并对大鼠口服脑复聪治疗12周。我们评估了认知功能，并测量了神经元损伤、氧化应激损伤以及IDE、Aβ、淀粉样前体蛋白（APP）、p-Tau和ERK/JNK/p38 MAPK通路成分的表达水平。糖尿病大鼠在认知功能、神经元损伤、氧化应激、IDE低表达、Aβ积累、APP高表达、Tau磷酸化异常以及ERK/JNK/p38 MAPK通路过度激活方面表现出显著下降。脑复聪治疗显著逆转了这些症状。我们的研究结果表明，脑复聪通过抑制ERK/JNK/p38 MAPK通路、上调IDE、减少Aβ沉积、抑制APP和p-Tau表达以及减轻神经元损伤和氧化应激来改善糖尿病大鼠的认知障碍。本研究为临床使用中药脑复聪预防和治疗DCI提供了参考。
