Wang Caixia, Ren Huilin, Wang Zhen, Min Ruixue, Chen Xiaoli, Ma Yanli, Zhang Xiaofeng
Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation, Nanyang Institute of Technology, Nanyang, Henan, China.
Neurogastroenterol Motil. 2025 Apr 28:e70065. doi: 10.1111/nmo.70065.
As a medicine-food fruit, Amomum tsao-ko has been reported to be beneficial for the management of diabetes. However, its effects and mechanisms in the cognitive impairment caused by diabetes remain unclear. This study aimed to investigate the influences of A. tsao-ko on cognitive impairment in type 2 diabetes mellitus (T2DM) mice and associated mechanisms.
A. tsao-ko was characterized using UHPLC-Q-Orbitrap-MS/MS. T2DM mice induced by a high-fat diet combined with streptozotocin were treated with ethanol extract of A. tsao-ko (EEAT) for 8 weeks. The cognitive function was evaluated by the Morris water maze (MWM) test, open field test (OFT), and novel object recognition test (NORT). Hippocampus and colon tissues were used for histopathology, biochemical assays, or protein expression analysis. Additionally, fecal samples were subjected to 16S rRNA gene sequencing and short-chain fatty acids (SCFAs) detection.
The findings demonstrated that EEAT significantly reversed glucose metabolism disorders and cognitive deficits in T2DM mice. It promoted the protein expression of the CREB/BDNF/TrkB pathway and reduced hippocampal inflammatory responses, thereby improving neuronal damage. It inhibited the loss of colonic tight junction proteins, decreased the levels of inflammatory factors in the colon, and also reshaped the gut microbiota and increased SCFAs. Notably, Spearman's correlation analysis indicated that the Lachnospiraceae NK4A136 group, Ruminococcaceae UCG-014, Lactobacillus, Blautia, and Lachnoclostridium were obviously correlated (positive or negative) with glucose homeostasis indexes, behavioral indexes, tissue inflammatory factors, and SCFAs.
The regulating effects of Amomum tsao-ko on gut microbiota, SCFAs, and the CREB/BDNF/TrkB pathway may be potential mechanisms for alleviating cognitive impairment in diabetes, which provides a potential option to treat diabetic cognitive impairment.
作为一种药食两用水果，草果已被报道对糖尿病的管理有益。然而，其在糖尿病所致认知障碍中的作用及机制仍不清楚。本研究旨在探讨草果对2型糖尿病（T2DM）小鼠认知障碍的影响及其相关机制。
采用超高效液相色谱-四极杆-轨道阱串联质谱（UHPLC-Q-Orbitrap-MS/MS）对草果进行表征。用高脂饮食联合链脲佐菌素诱导的T2DM小鼠，用草果乙醇提取物（EEAT）治疗8周。通过莫里斯水迷宫（MWM）试验、旷场试验（OFT）和新物体识别试验（NORT）评估认知功能。海马和结肠组织用于组织病理学、生化分析或蛋白质表达分析。此外，对粪便样本进行16S rRNA基因测序和短链脂肪酸（SCFAs）检测。
研究结果表明，EEAT显著逆转了T2DM小鼠的糖代谢紊乱和认知缺陷。它促进了CREB/BDNF/TrkB通路的蛋白表达，减轻了海马炎症反应，从而改善了神经元损伤。它抑制了结肠紧密连接蛋白的丢失，降低了结肠中炎症因子的水平，还重塑了肠道微生物群并增加了SCFAs。值得注意的是，Spearman相关性分析表明，毛螺菌科NK4A136组、瘤胃球菌科UCG-014、乳酸杆菌属、布劳特氏菌属和粪球菌属与糖稳态指标、行为指标、组织炎症因子和SCFAs明显相关（正相关或负相关）。
草果对肠道微生物群、SCFAs和CREB/BDNF/TrkB通路的调节作用可能是减轻糖尿病认知障碍的潜在机制，为治疗糖尿病认知障碍提供了一个潜在选择。
