Hu Nanzhi, Wang Kaiyue, Ge Xing, Zhang Xin, Zheng Xiaojie, Sun Shifang
Department of Geriatrics, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Ningbo Cadre Health Center, Ningbo, China.
Front Pharmacol. 2025 Jun 26;16:1562775. doi: 10.3389/fphar.2025.1562775. eCollection 2025.
As we get older, we experience a variety of symptoms such as memory and cognitive decline in learning. In the process of aging, neuroinflammatory response is one of the main reasons for the occurrence of cognitive dysfunction. flower flavonoids (DOFF) can effectively regulate the structure of intestinal microbiota, antioxidant and anti-inflammatory functions.
DOFF samples were extracted by water extraction assisted ultrasonic ethanol method. The DOFF composition was determined by LC-MS/MS method. An aging mouse model was established using D-galactose (D-gal) induced mice. 16S rDNA sequencing was used to analyze intestinal flora, hematoxylin/eosin staining (H&E) and immunohistochemical staining were used to analyze colonic and hippocampal tissue damage and related proteins, and ElISA was used to determine related inflammatory factors. The Y-maze experiment was used to test the cognitive ability of mice, the expression of related synaptic protein was detected by WB, and Iba-1 was labeled by immunofluorescence to study the effects of DOFF on inflammatory response and cognitive function by regulating intestinal microbiota.
The results showed that DOFF intervention could regulate the relative abundance of intestinal flora in D-gal mice, including the relative abundance of , down-regulate the ratio of up-regulate the expression of ZO-1, and improve the colonic tissue injury. In addition, by inhibiting the production of MDA, increasing the activity of SOD, CAT and POD, inhibiting the expression of pro-inflammatory factors TNF-α, IL-6 and IL-1β, inhibiting the activation of microglia, and effectively improving the oxidative stress damage and inflammation caused by aging. By increasing the expression of related synaptic proteins, upregulation of BDNF levels improves synaptic plasticity and alleviates cognitive dysfunction.
DOFF can improve cognitive dysfunction by regulating intestinal microbiota composition, enhancing intestinal barrier integrity in D-GAL-induced aging mice, improving neuroinflammation, and alleviating hippocampal neuron damage.
随着年龄的增长,我们会经历各种症状,如学习中的记忆力和认知能力下降。在衰老过程中,神经炎症反应是认知功能障碍发生的主要原因之一。花黄酮(DOFF)能有效调节肠道微生物群的结构、抗氧化和抗炎功能。
采用水提取辅助超声乙醇法提取DOFF样品。采用LC-MS/MS法测定DOFF的成分。用D-半乳糖(D-gal)诱导小鼠建立衰老小鼠模型。采用16S rDNA测序分析肠道菌群,苏木精/伊红染色(H&E)和免疫组化染色分析结肠和海马组织损伤及相关蛋白,采用酶联免疫吸附测定法(ElISA)测定相关炎症因子。采用Y迷宫实验检测小鼠的认知能力,通过蛋白质免疫印迹法(WB)检测相关突触蛋白的表达,通过免疫荧光法标记离子钙结合衔接分子-1(Iba-1),研究DOFF通过调节肠道微生物群对炎症反应和认知功能的影响。
结果表明,DOFF干预可调节D-gal小鼠肠道菌群的相对丰度,包括[具体菌群名称1]的相对丰度,下调[具体菌群名称2]的比例,上调闭锁小带蛋白1(ZO-1)的表达,并改善结肠组织损伤。此外,通过抑制丙二醛(MDA)的产生,增加超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和过氧化物酶(POD)的活性,抑制促炎因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)的表达,抑制小胶质细胞的激活,有效改善衰老引起的氧化应激损伤和炎症。通过增加相关突触蛋白的表达,上调脑源性神经营养因子(BDNF)水平,改善突触可塑性,减轻认知功能障碍。
DOFF可通过调节肠道微生物群组成、增强D-GAL诱导的衰老小鼠肠道屏障完整性、改善神经炎症和减轻海马神经元损伤来改善认知功能障碍。