Exploring the mechanism of BuNao AnShen Capsules in the treatment of insomnia based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: BuNao AnShen Capsules (BNASC), a Traditional Chinese Medicine (TCM), is widely used to treat insomnia, yet its effective components and targets remain largely unidentified.

AIM OF THE STUDY: The present work thoroughly assessed sedative-hypnotic efficacy of BNASC in managing insomnia and elucidated its associated action mechanism by network pharmacology plus experiments.

MATERIALS AND

METHODS

Network pharmacology and molecular docking identified the effective components and targets of BNASC and their binding affinities. A Para-chlorophenylalanine (PCPA) induced insomnia mouse model was created to evaluate BNASC's sedative-hypnotic effects using the open-field test (OFT) and pentobarbital sodium-induced sleep test (PIST). Enzyme-linked immunosorbent assays measured neurotransmitter levels, inflammatory factors, and oxidative stress. Additionally, BNASC's effect on the GABAA1 receptor was evaluated using the patch-clamp technique.

RESULTS

We identified 100 effective components associated with 184 overlapping drug- and disease-related targets in BNASC. Pharmacological analysis indicated that body weights in the treatment groups increased compared to the model group (P < 0.05). The high-dose BNASC group displayed superior sedative-hypnotic effects compared to the positive control (Ramelteon), evidenced by reduced activity and movement in the OFT, and increased sleep duration in the PIST. BNASC enhanced levels of 5-HT, IL-1β, TNF-α, and SOD activity, while it reduced NE, DA, IL-6, and MDA levels in a dose-dependent manner in the hypothalamus of PCPA-induced insomniac mice. Additionally, combined results from cellular and animal studies indicated that BNASC did not significantly affect GABA in either context.

CONCLUSIONS

This study confirmed the sedative-hypnotic efficacy of BNASC and revealed its underlying mechanisms related to neurotransmitters, inflammatory cytokines, and oxidative stress, providing a theoretical basis for its clinical application.