Banxia Shumi Decoction Alleviates PCPA-Induced Insomnia and Regulates ADAM10 Expression via Melatonin Signaling in Rats
Abstract
Background: Insomnia is a pathological sleep disorder marked by persistent sleep-onset difficulties. This study explored the therapeutic effects and underlying mechanism of Banxia Shumi Decoction (BXSMD) in treating insomnia.
Methods: This study used network pharmacology to predict the core targets and signaling pathways of BXSMD in insomnia intervention. A rat insomnia model was constructed via 4-Chloro-DL-phenylalanine (PCPA) to assess BXSMD's behavioral impacts. ELISA, qRT-PCR, Western blot, and IHC were applied to detect the expression of 5-hydroxytryptamine (5-HT), melatonin (MT), MT1/MT2 receptors, and related factors (CLOCK, PER1, CaMKII, p-CREB/CREB, GABARAP, mGLuR1, ADAM10) in the rat suprachiasmatic nucleus (SCN), hippocampus, and serum. The non-selective melatonin receptor antagonist luzindole was administered to explore its influence on BXSMD-regulated expression of the above molecules.
Results: Compared with the model group, the BXSMD group showed shortened sleep latency and prolonged sleep duration. BXSMD significantly elevated 5-HT, MT, and MT1/MT2 levels. BXSMD upregulated the mRNA and protein expression of downstream effector molecules including CLOCK, PER1, CaMKII, and GABARAP, downregulated mGLuR1 expression, and increased the expression of ADAM10. Notably, CREB mRNA expression remained unchanged, while BXSMD significantly increased the p-CREB/CREB protein ratio. The regulatory effects of BXSMD on all altered molecules were significantly reversed by…
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