The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
Comb Chem High Throughput Screen. 2024;27(17):2565-2582. doi: 10.2174/0113862073255849231030114405.
Diabetic cognitive dysfunction (DCD) is emerging as a chronic complication of diabetes that is gaining increasing international recognition. The traditional Chinese medicine (TCM) formulation, Tangzhiqing decoction (TZQ), has shown the capacity to modulate the memory function of mice with DCD by ameliorating insulin resistance. Nevertheless, the precise mechanism underlying the effects of TZQ remains elusive.
The chemical constituents of TZQ were screened using TCMSP databases, and DCDassociated disease targets were retrieved from various databases. Subsequently, core targets were identified through network topology analysis. The core targets underwent analysis using Gene Ontology (GO) functional annotations and enrichment in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Models were established through high-fat and high-glucose diet feeding along with intraperitoneal injection of streptozotocin (STZ). TZQ and metformin were administered at varying doses over 8 weeks. The Morris water maze was employed to evaluate the cognitive capabilities of each rat group, while indicators of oxidative stress and insulin were assessed in mice. Neuronal apoptosis in distinct groups of mice's hippocampi was detected using TdT-mediated dUTP Nick-End Labeling (TUNEL), and western blot (WB) analysis was conducted to assess the expression of apoptosis- and autophagy-related proteins, including Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, LC3, p62, and Lamp2, within the hippocampus.
TZQ exhibited the capacity to modulate neuronal autophagy, ameliorate endoplasmic reticulum stress, apoptosis, inflammation, and oxidative stress, as well as to regulate synaptic plasticity and conduction. TZQ mitigated cognitive dysfunction in mice, while also regulating hippocampal inflammation and apoptosis. Additionally, it influenced the protein expression of autophagy-related factors such as Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, and LC3. Notably, this modulation significantly reduced neuronal apoptosis in the hippocampus and curbed excessive autophagy.
TZQ demonstrated a substantial reduction in neuronal apoptosis within the hippocampus and effectively suppressed excessive autophagy.
糖尿病认知功能障碍（DCD）是糖尿病的一种慢性并发症，正逐渐受到国际关注。中药方剂糖脂清（TZQ）通过改善胰岛素抵抗，显示出调节 DCD 小鼠记忆功能的能力。然而，TZQ 作用的确切机制仍不清楚。
利用 TCMSP 数据库筛选 TZQ 的化学成分，从各种数据库中检索与 DCD 相关的疾病靶点。然后，通过网络拓扑分析确定核心靶点。对核心靶点进行基因本体（GO）功能注释和京都基因与基因组百科全书（KEGG）通路富集分析。通过高脂高糖饮食喂养和腹腔注射链脲佐菌素（STZ）建立模型。用不同剂量的 TZQ 和二甲双胍治疗 8 周。采用 Morris 水迷宫评估各组大鼠的认知能力，检测各组小鼠的氧化应激和胰岛素指标。用末端转移酶介导的 dUTP 缺口末端标记（TUNEL）检测不同组小鼠海马神经元凋亡情况，用 Western blot 分析检测海马凋亡和自噬相关蛋白（Bax、Bcl2、Caspase3、Caspase8、Beclin1、ATG7、LC3、p62、Lamp2）的表达。
TZQ 可调节神经元自噬，改善内质网应激、凋亡、炎症和氧化应激，调节突触可塑性和传导。TZQ 减轻了小鼠的认知功能障碍，同时调节了海马的炎症和凋亡。此外，它还影响了自噬相关因子（如 Bax、Bcl2、Caspase3、Caspase8、Beclin1、ATG7 和 LC3）的蛋白表达。值得注意的是，这种调节显著减少了海马神经元凋亡，抑制了过度自噬。
TZQ 可减少海马神经元凋亡，有效抑制过度自噬。
