Integrating network pharmacology and multi-omics to explore the mechanism of Callicarpa kwangtungensis Chun in ameliorating Alzheimer's disease pathology in APP/PS1 mice

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2024-11-23 DOI:10.1016/j.jep.2024.119148

Yong-lin Liu , Sha Xu , Xi Xu , Yuan Tang , Jian Shao , Jie Chen , Yi-guang Li

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Abstract

Ethnopharmacological relevance

Callicarpa kwangtungensis Chun (CK) is a traditional herb for the treatment of blood stasis, hemostasis, anti-inflammation, and antidepressant. Previous studies have showen that CK extract has significant anti-neuroinflammatory activity. However, the mechanism by which it treats AD is still unclear.

Aim of study

This study aimed to investigate the effects and mechanisms of CK in ameliorating AD pathology using in vivo and in vitro models, supported by a multi-omics analysis approach.

Materials and methods

The chemical composition of CK was characterized using UPLC-QE Plus-MS/MS. The effects and mechanisms of CK on AD pathology were then investigated using APP/PS1 mice and BV2 and HT22 cell models, with comprehensive insights provided by network pharmacology, transcriptomics, and metabolomics analyses.

Results

This study is the first to report the identification of 146 compounds from CK. CK administration led to significant improvements in cognitive function, reduced amyloid-beta and neurofibrillary tangle formation, and inhibited the activation of microglia and astrocytes in APP/PS1 mice. Comprehensive analyses suggest that CK may modulate the TCA cycle through the PI3K-AKT signaling pathways and inflammation-related MAPK and NF-κB signaling pathways. In vitro studies revealed that CK significantly inhibited LPS-induced inflammation and oxidative stress in BV2 cells, as well as reduced oxidative stress and neuronal apoptosis in HT22 cells.

Conclusion

These findings underscore the potential of CK as a therapeutic agent in alleviating AD pathology. This study offers new insights into CK's mechanisms, suggesting that its therapeutic effects may be achieved through the coordinated reduction of neuroinflammation, oxidative stress, and neuronal apoptosis across multiple pathways, collectively working to counteract AD pathology.

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整合网络药理学和多组学探索春黄芩改善APP/PS1小鼠阿尔茨海默病病理变化的机制

民族药理学意义：Callicarpa kwangtungensis Chun（CK）是一种传统草药，用于治疗血瘀、止血、抗炎和抗抑郁。先前的研究表明，CK 提取物具有显著的抗神经炎活性。然而，其治疗 AD 的机制仍不清楚：本研究旨在利用体内和体外模型，在多组学分析方法的支持下，研究 CK 在改善 AD 病理学方面的作用和机制：采用UPLC-QE Plus-MS/MS对CK的化学成分进行表征。然后利用APP/PS1小鼠、BV2和HT22细胞模型研究了CK对AD病理学的影响和机制，并通过网络药理学、转录组学和代谢组学分析提供了全面的见解：本研究首次报告了从 CK 中鉴定出的 146 种化合物。服用 CK 能明显改善 APP/PS1 小鼠的认知功能，减少淀粉样蛋白-β 和神经纤维缠结的形成，并抑制小胶质细胞和星形胶质细胞的活化。综合分析表明，CK 可通过 PI3K-AKT 信号通路以及与炎症相关的 MAPK 和 NF-κB 信号通路调节 TCA 循环。体外研究显示，CK 能显著抑制 LPS 诱导的 BV2 细胞炎症和氧化应激，并能减少 HT22 细胞的氧化应激和神经元凋亡：这些发现强调了 CK 作为一种治疗药物在缓解 AD 病理学方面的潜力。这项研究为 CK 的作用机制提供了新的见解，表明其治疗效果可能是通过协调减少神经炎症、氧化应激和神经元凋亡等多种途径实现的，从而共同对抗 AD 病理学。

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.