Efficacy and mechanisms of action of Shangxia Liangji formula in the treatment of insomnia

Abstract

Aims: Shangxia Liangji formula (SXLJF) is a traditional Chinese medicine formula used clinically for the treatment of insomnia. However, the exact mechanism of SXLJF remains unclear.

Methods and Results: A mouse insomnia model was established by intraperitoneal injection of p-chlorophenylalanine. Control, model, low/medium/high-dose SXLJF (9.26, 18.72, and 37.44 g/kg/day), and diazepam (2 mg/kg) groups were treated with designated reagents for 7 days. Behavioral changes were assessed via open field and pentobarbital-induced sleep tests. Hippocampal histopathology was evaluated using HE, Nissl, and TUNEL staining. Levels of serotonin (5-HT), 5-HIAA, dopamine (DA), norepinephrine (NE), IL-1β, IL-6, and TNF-α were measured using ELISA. RT-qPCR and immunofluorescence were used to analyze glial fibrillary acidic protein (GFAP), neuronal nuclei (NeuN), and brain-derived neurotrophic factor (BDNF) expression. Behavioral tests showed that SXLJF reduced mouse total distance traveled, average velocity, central distance, and sleep latency but increased sleep duration. It also attenuated expression of IL-1β, IL-6, and TNF-α, modulated levels of the monoamine neurotransmitters 5-HT, 5-HIAA, NE, and DA, upregulated NeuN and BDNF expression, downregulated GFAP expression, inhibited astrocyte activation, and mitigated neuronal apoptosis.

Conclusion: The mechanism underlying SXLJF’s anti-insomnia effect may be related to the regulation of monoamine neurotransmitters, inhibition of astrocyte activation and inflammatory factors, and suppression of neuronal apoptosis.

Keywords

apoptosis / astrocyte / inflammatory factors / insomnia / neuron / neurotransmitter / Shangxia Liangji formula

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