From Mechanistic Evidence to Clinical Translation: A Narrative Review of Chinese Herbal Medicine for Insomnia

Abstract: Insomnia is one of the most common sleep disorders and a major public health problem worldwide. Chinese herbal medicine (CHM) is widely used as a complementary and alternative approach for chronic insomnia. Clinical studies have reported preliminary evidence of benefit for Chinese herbal formulas, whereas mechanistic research has examined single herbs, extracts, active constituents, and compound formulas using multi-omics analysis, network pharmacology, molecular prediction, and experimental validation. However, clinical studies are typically small and of inconsistent methodological quality, with limited long-term follow-up, while mechanistic evidence remains fragmented and lacks systematic integration and translational validation. These limitations restrict the development of CHM interventions from experimental evidence to clinically testable interventions for insomnia. This narrative review evaluates existing research across five translational dimensions, namely chemical characterization and preparation quality, exposure and pharmacodynamic evidence, mechanism and target validation, sleep-related clinical endpoints, and safety. It aims to clarify the current state of research on CHM interventions for insomnia and to identify key limitations and priorities for future research. Most available evidence comes from preclinical studies, which suggest that CHM may influence sleep-related processes through γ-aminobutyric acid (GABA) and serotonergic signaling, the hypothalamic-pituitary-adrenal (HPA) axis, neuroinflammation, oxidative stress, apoptosis-autophagy balance, and the brain-gut-microbiota axis. Much of this evidence reflects changes in biochemical markers or pathway activity, while only a few studies directly test target function. Clinical studies provide preliminary evidence of short-term improvements in subjective sleep outcomes. However, clinical translation remains limited by insufficient evidence for objective sleep improvement and long-term efficacy and safety. Future work should carry a few well-characterized interventions through the full evidence chain, prioritizing standardized preparations, exposure and pharmacodynamic assessment, objective sleep endpoints, long-term follow-up, and safety. Keywords: Chinese herbal medicine, insomnia, neurobiological mechanisms, active constituents, herbal formulas, clinical evidence