陈皮素改善瑞士小鼠的记忆，通过动物行为评估和计算机模拟研究揭示潜在的分子干预作用。

Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies.

作者信息

Al Hasan Md Sakib, Khan Mohd Shahnawaz, Ayub Arusha, Chowdhury Raihan, Mia Emon, Shadin Md, Akbor Md Showkot, Islam Muhammad Torequl, Bhuia Md Shimul

机构信息

Department of Pharmacy, Goapalganj Science and Technology University, Gopalganj, Bangladesh.

Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj, Bangladesh.

出版信息

Brain Behav. 2025 May;15(5):e70516. doi: 10.1002/brb3.70516.

DOI:10.1002/brb3.70516

PMID:40320970

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12050655/

Abstract

INTRODUCTION

Tangeretin (TAN), a polymethoxylated flavone from citrus peels, exhibits neuroprotective, anti-inflammatory, and antioxidant properties. This study aims to evaluate the memory-enhancing effects of TAN in Swiss mice and explore its potential molecular interactions with the D dopamine (DOP) receptor through in vivo behavioral assessments and in silico approaches.

METHODS

Swiss mice were administered TAN (10 and 20 mg/kg), DOP (22 mg/kg), and olanzapine (OLN) (2 mg/kg), alone and in combinations per orally (p.o.), followed by cognitive assessments using marble burying, dust removal, and trained swimming tests. In silico studies included molecular docking against the D receptor (PDB: 6CM4), pharmacokinetics (SwissADME, pkCSM), and toxicity predictions (ProTox-3).

RESULTS

TAN significantly (p < 0.05) improved cognitive functions, including memory, anxiety, and motor coordination, in a dose-dependent manner, with 20 mg/kg showing the most notable effect. The combination of TAN-10 with DOP-22 enhanced these benefits, whereas TAN-10 with OLN-2 reduced cognitive improvements. TAN-treated Swiss mice showed better performance in marble burying, dust removal, and trained swimming tests, indicating enhanced memory, problem-solving, and motor coordination. These results suggest TAN's potential in cognitive enhancement, particularly with DOP-22. No deaths were observed in any treatment group, and all treated animals exhibited normal physiological activity with no signs of acute toxicity. In silico studies revealed that TAN exhibited the strongest binding affinity (BA) (-6.6 kcal/mol) with the D receptor, forming multiple hydrogen bonds (HBs), which indicates its potential mechanism for memory enhancement via dopaminergic modulation. Pharmacokinetic analyses also showed that TAN has favorable ADMET properties, including high gastrointestinal absorption, blood-brain barrier penetration, and low toxicity.

CONCLUSION

These findings highlight TAN's potential as a promising therapeutic candidate for memory-related disorders, warranting further clinical exploration.

摘要

引言

陈皮素（TAN）是一种来自柑橘皮的多甲氧基黄酮，具有神经保护、抗炎和抗氧化特性。本研究旨在评估TAN对瑞士小鼠记忆增强的作用，并通过体内行为评估和计算机模拟方法探索其与D多巴胺（DOP）受体潜在的分子相互作用。

方法

给瑞士小鼠口服给予TAN（10和20mg/kg）、DOP（22mg/kg）和奥氮平（OLN）（2mg/kg），单独给药及联合给药，随后通过埋珠试验、除尘试验和训练游泳试验进行认知评估。计算机模拟研究包括与D受体（PDB：6CM4）的分子对接、药代动力学（SwissADME，pkCSM）和毒性预测（ProTox-3）。

结果

TAN以剂量依赖性方式显著（p<0.05）改善认知功能，包括记忆、焦虑和运动协调，20mg/kg显示出最显著的效果。TAN-10与DOP-22联合使用增强了这些益处，而TAN-10与OLN-2联合使用则降低了认知改善效果。经TAN处理的瑞士小鼠在埋珠试验、除尘试验和训练游泳试验中表现更好，表明记忆、解决问题和运动协调能力增强。这些结果表明TAN在认知增强方面具有潜力，特别是与DOP-22联合使用时。在任何治疗组中均未观察到死亡，所有接受治疗的动物均表现出正常的生理活动，无急性毒性迹象。计算机模拟研究表明，TAN与D受体表现出最强的结合亲和力（BA）（-6.6kcal/mol），形成多个氢键（HBs），这表明其通过多巴胺能调节增强记忆的潜在机制。药代动力学分析还表明，TAN具有良好的ADMET特性，包括高胃肠道吸收、血脑屏障穿透性和低毒性。