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

Abstract

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&#xa0;<&#xa0;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-1&#x3b2;, TNF-&#x3b1;, 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.