随着人口老龄化的加剧，认知障碍已成为全球公共卫生重大挑战。高脂饮食（High-Fat Diet, HFD）作为现代生活常见的不良饮食模式，已被证实与认知功能障碍及多种神经退行性疾病密切相关。然而，目前针对HFD诱导的认知障碍仍缺乏安全、有效的天然干预策略。

近年来，茶饮类功能性食品在代谢性疾病与神经退行性病变的防治中展现出良好前景。藤茶（Nekemias grossedentata），作为我国南方传统的茶饮植物，富含多种黄酮类活性成分。前期研究已证明其在抗肥胖、调节肠道菌群等方面具有多种生物活性，但其在HFD相关认知障碍中的干预作用及潜在机制尚不明确。本研究基于HFD诱导的肥胖型认知障碍小鼠模型，结合多组学技术，探究藤茶水提物及其主要成分双氢杨梅素的改善作用及潜在机制。主要研究内容与结果如下：

1. 藤茶化学成分的系统解析

结合日常饮用方式，本研究以藤茶水提物为研究对象，采用非靶向代谢组学结合靶向定量分析技术，首次全面解析藤茶水提物化学组成，共鉴定出2465种化合物，其中黄酮类占比最高（629种，总黄酮含量高达527.9 ± 20.7 mg/g）。靶向分析进一步明确双氢杨梅素（Dihydromyricetin, DHM）为藤茶中最主要的核心成分，含量为3.44 ± 1.30 mg/g，显著高于其他黄酮类成分。

2. 藤茶改善HFD小鼠认知障碍的药效评价

连续14周高脂饮食喂养成功建立小鼠认知障碍模型，藤茶水提物可显著改善HFD诱导的糖脂代谢紊乱，表现为抑制脂质积累、降低血糖水平以及增强葡萄糖与胰岛素耐受性。认知行为学实验（新物体识别实验和Morris水迷宫实验）和海马组织H＆E染色病理学分析结果表明，藤茶可显著提升小鼠的学习记忆能力，并有效缓解海马神经元损伤，首次明确藤茶可显著改善HFD相关认知障碍

3. 基于多组学的藤茶作用机制研究

结合WB、IF、IHC、RT-qPCR、ELISA等分子生物学、宏基因组及代谢组学技术进一步探讨藤茶水提物的作用机制。结果显示，藤茶通过调节关键菌种丰度（如上调Porphyromonas loveana、Parabacteroides faecis、Gordonibacter pamelaeae等有益菌种，下调Eggerthella lenta、Olsenella uli等有害菌种），有效逆转HFD诱导的肠道菌群失调，降低肠道炎症介质白三烯的合成，恢复抗炎代谢物短链脂肪酸（SCFAs）的水平，修复肠黏膜屏障功能，减少炎症因子外溢，从而抑制全身性炎症反应。进一步分析表明，藤茶通过“微生物-肠-脑轴”机制减轻了模型小鼠海马区的炎症反应。一方面抑制神经炎症破坏神经突触结构，另一方面通过维持SIRT1正常表达改善外周代谢紊乱所引发的大脑胰岛素信号通路异常，保护神经元突触功能。

综上所述，本研究首次明确藤茶水提物可显著改善HFD小鼠的认知功能障碍。其主要机制涉及肠道微生态重塑、代谢产物谱优化，及神经炎症抑制。本研究从“微生物-肠-脑轴”视角揭示了藤茶干预HFD相关认知障碍的潜在机制，不仅为藤茶开发为功能性食品提供了理论依据，也为天然活性成分在代谢性与神经功能障碍中的应用探索提供了新思路。

With the accelerating pace of global population aging, cognitive impairment has become a major public health challenge worldwide. High-fat diet (HFD), a prevalent unhealthy dietary pattern in modern lifestyles, has been strongly associated with cognitive dysfunction and various neurodegenerative diseases. However, safe, and effective natural intervention strategies for HFD-induced cognitive impairment remain lacking.

In recent years, tea-based functional foods have shown promising potential in the prevention and treatment of metabolic disorders and neurodegenerative diseases. Nekemias grossedentata, commonly known as vine tea and traditionally consumed in southern China, is rich in flavonoid compounds. Previous studies have demonstrated its various bioactivities, including anti-obesity effects and modulation of gut microbiota. However, its potential role and underlying mechanisms in alleviating HFD-related cognitive impairment have not been fully elucidated. In this study, based on an HFD-induced obese mouse model with cognitive dysfunction, we employed multi-omics approaches to investigate the therapeutic effects and potential mechanisms of vine tea water extract and its major component, dihydromyricetin (DHM). The main contents and findings are as follows:

1. Systematic characterization of the chemical composition of vine tea

Based on common consumption practices, the water extract of vine tea was selected as the study material. Using a combination of untargeted metabolomics and targeted quantitative analysis, we comprehensively profiled the chemical constituents of the extract for the first time. A total of 2,465 compounds were identified, among which flavonoids accounted for the largest proportion (629 species), with a total flavonoid content of 527.9 ± 20.7 mg/g. Targeted analysis further identified DHM as the primary flavonoid in vine tea, with a content of 3.44 ± 1.30 mg/g—significantly higher than other flavonoid components.

2. Evaluation of the efficacy of vine tea in improving HFD-induced cognitive impairment

A mouse model of cognitive dysfunction was successfully established after 14 weeks of HFD feeding. Vine tea water extract significantly improved HFD-induced glucose and lipid metabolic disorders, as evidenced by reduced lipid accumulation, lowered blood glucose levels, and enhanced glucose and insulin tolerance. Behavioral tests (novel object recognition and Morris water maze) and histological analysis of the hippocampus demonstrated that vine tea markedly enhanced learning and memory abilities and alleviated neuronal damage in the hippocampus, providing the first evidence that vine tea effectively mitigates HFD-related cognitive impairment.

3. Mechanistic study of vine tea based on multi-omics analysis

Using molecular biology, metagenomics, and metabolomics approaches, the underlying mechanisms of vine tea extract were further explored. Results showed that vine tea modulated gut microbiota composition by increasing beneficial bacteria (e.g., Porphyromonas loveana, Parabacteroides faecis, Gordonibacter pamelaeae) and reducing harmful ones (e.g., Eggerthella lenta, Olsenella uli), thereby reversing HFD-induced gut dysbiosis. This modulation led to reduced synthesis of pro-inflammatory leukotrienes, restoration of anti-inflammatory short-chain fatty acids (SCFAs), improved intestinal barrier integrity, and reduced systemic inflammatory spillover. Further analysis suggested that vine tea alleviated hippocampal inflammation through the "microbiota–gut–brain axis." On one hand, it suppressed neuroinflammation-mediated synaptic damage; on the other, it activated SIRT1 to improve insulin signaling disrupted by peripheral metabolic disorders, thus preserving neuronal synaptic function.

This study provides the first clear evidence that vine tea water extract significantly improves HFD-induced cognitive dysfunction. The primary mechanisms involve remodeling of the gut microbiota, optimization of metabolic profiles, and suppression of neuroinflammation. From the perspective of the “microbiota–gut–brain axis,” this research elucidates the potential mechanisms of vine tea in ameliorating HFD-related cognitive impairment, offering a theoretical basis for the development of vine tea as a functional food and shedding new light on the application of natural bioactive compounds in metabolic and neurological disorders.