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Mechanism of Herbal Pairs Modulating Endogenous Melatonin to Ameliorate Sleep Disorders: Data Mining, Network Pharmacology and Meta-Analysis

Zhenwei Zhai, Jingyi Dai, Fanjing Kong, Zhishan Zhu, Jie Cai, Danni Xie, Sha Huang, Tao Jiang et al.

Combinatorial chemistry & high throughput screening, 2025

1 citation

Abstract

INTRODUCTION

Sleep disorders (SD) affect approximately 25% of the global population. Traditional Chinese Medicine (TCM) formulas have been shown to alleviate SD by modulating endogenous melatonin. This study used data mining, network pharmacology, and meta-analysis to identify key herbal pairs from TCM formulas and the mechanism of action.

METHODS

Literature was retrieved from PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data Information Site, China Science and Technology Journal Database, and SinoMed. R was used for frequency and association rule analysis, SPSS for clustering, and Cytoscape, STRING, Gene Ontology, and KEGG enrichment analyses were utilized to explore targets, protein-protein interactions, and pathways. A meta-analysis using the Metan command was performed to assess the optimal herbal pairs for SD treatment.

RESULTS

Data mining identified 77 commonly used herbs, revealing four advantageous herbal pairs: PAEONIAE RADIX ALBA (PRA)-BUPLEURI RADIX (BR), COPTIDIS RHIZOMA (CR)- CINNAMOMI CORTEX (CC), PORIA (PA)-BUPLEURI RADIX (BR), and ZIZIPHI SPINOSAE SEMEN (ZSS)-MARGARITIFERA CONCHA (MC). Network pharmacology showed that (PRA-BR)-SD, (PA-BR)-SD, (CR-CC)-SD, and (ZSS-MC)-SD targeted CACNA1D, GRIN2A, AGT, and ATP1A1 via prion diseases, nicotine addiction, neuroactive ligand-receptor interaction, and cardiac muscle contraction pathways, respectively.

DISCUSSION

Research shows that CACNA1D could regulate Ca²⁷ inward flow, avoid mitochondrial…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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