基于生物信息学和网络药理学的霍山大叶黄茶治疗糖尿病认知功能障碍机制研究

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-07 DOI:10.1016/j.phymed.2025.156923

Rui Li , Qi Lou , Yu Zhu , Min Si , Xiaoyu Zhu , Huiyu Jia , Haoran Yang , Tingting Ji , Dongrui Xu , Wulin Yang , Shengyong Luo , Yijun Wang

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引用次数: 0

摘要

糖尿病认知功能障碍（DCD）是糖尿病的一种常见并发症，以进行性认知功能下降为特征。目前的药物干预对这种疾病的治疗效果有限。从山茶叶中提取的霍山大叶黄茶（HLYT）具有调节血糖和增强认知的双重药理作用，提示其具有预防和治疗DCD的潜力。目的阐明HLYT对DCD的调控作用，并探讨其机制。研究设计本研究包括一个全面的多阶段调查。网络药理学分析确定了HLYT对DCD的关键靶基因。分子对接筛选枢纽靶基因，并通过分子动力学（MD）模拟进一步验证。高效液相色谱法（HPLC）定量测定了HLYT的有效成分，确定了动物实验剂量。采用高脂饲料喂养并注射链脲佐菌素（STZ）建立大鼠DCD模型。随后，大鼠灌胃给予HLYT干预。然后通过相关动物实验验证该干预的结果。结果利用网络药理学和分子对接相结合的方法，确定了5个关键靶基因（Adora2a、Mapk8、Stat3、Vcam1、Edn1）是HLYT在DCD发病中的主要分子靶点。HLYT中的槲皮素、山奈酚、咖啡因、可可碱和EGCG与这些靶点表现出显著的结合亲和力。动物实验结果表明，HLYT能减轻DCD大鼠的神经元损伤和认知功能障碍，降低血清和脑组织中IL-6和IL-1β的水平。此外，它还能抑制Adora2a、Mapk8、Stat3、Vcam1、Edn1 mRNA的表达，以及Stat3、Adora2a、JNK1、ET1、Vcam1蛋白的表达。结论hlyt通过调节Adora2a、Mapk8、Stat3、Vcam1和Edn1基因对大鼠DCD有显著的保护作用，提示其在治疗DCD方面具有显著的临床潜力。

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Mechanism of Huoshan large-leaf yellow tea in treatment of diabetic cognitive dysfunction based on bioinformatics and network pharmacology

Background

Diabetic cognitive dysfunction (DCD) is a prevalent complication of diabetes, characterized by progressive cognitive decline. Current pharmacological interventions have limited therapeutic efficacy in managing this condition. Huoshan large - leaf yellow tea (HLYT), derived from Camellia sinensis leaves, has demonstrated dual pharmacological properties in both glycemic regulation and cognitive enhancement, suggesting its potential as a preventive and therapeutic agent for DCD.

Purpose

The main purpose of this study was to clarify the regulatory effect of HLYT on DCD and explore its underlying mechanisms.

Study design

The research encompassed a comprehensive multi-phase investigation. Network pharmacological analysis identified HLYT's key target genes for DCD. Molecular docking screened hub target genes, which were further verified by molecular dynamic (MD) simulations. High-performance liquid chromatography (HPLC) quantified HLYT's active components for setting animal experiment dosages. A DCD model was established in rats by feeding them a high - fat diet and injecting streptozotocin (STZ). Subsequently, HLYT was administered to the rats via intragastric gavage for intervention. The results of this intervention were then verified through relevant animal experiments.

Results

Utilizing an integrated approach of network pharmacology and molecular docking, five pivotal target genes (Adora2a, Mapk8, Stat3, Vcam1, Edn1) were identified as the primary molecular targets of HLYT in DCD pathogenesis. Quercetin, kaempferol, caffeine, theobromine, and EGCG in HLYT exhibited significant binding affinities with these targets. The results of animal experiment have shown that HLYT can alleviate neuronal damage and cognitive dysfunction, reduce the levels of IL-6 and IL-1β in the serum and brain tissue in DCD rats. Furthermore, it can also inhibit the expression of Adora2a, Mapk8, Stat3, Vcam1, and Edn1 mRNA as well as the expression of STAT3, ADORA2A, JNK1, ET1, and VCAM1 proteins.

Conclusion

HLYT has a significant protective effect on DCD in rats by regulating Adora2a, Mapk8, Stat3, Vcam1, and Edn1 genes, suggesting that it has remarkable clinical potential in the treatment of DCD.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.