Modified Suanzaoren Decoction (MSZRD), an improved traditional Chinese herbal recipe, effectively enhances sleep and regulates circadian rhythm disorders in mice experiencing insomnia.
To evaluate MSZRD's impact, we established an insomnia model in ICR mice with 14 days of multifactorial stimulation and subsequent intraperitoneal injections of a PCPA suspension for two straight days. We then administered three different doses of MSZRD to these mice for 24 days. In addition to measuring the food intake and back temperature, behavioural tests and pentobarbital sodium-induced sleep tests were carried out. We used ELISA kits to measure the levels of Orexin-A, CRH, ACTH, CORT in the serum and 5-HT, DA, and NE, in the hypothalamus. Additionally, GABA and glutamic acid levels were assessed through high-performance liquid chromatography, and 5-HTR1A receptor and orexin receptor 2 antibody expressions were done via Western blotting and immunohistochemical staining. Lastly, we examined the hypothalamus tissue's histological changes through hematoxylin and eosin and Nissl staining.
Observations revealed that MSZRD significantly improved sleep patterns, including latency and duration, mitigated circadian rhythm disruptions, enhanced the content of 5-HT and 5-HTR1A protein, and reduced DA and NE content in the hypothalamus of insomnia mice. Further, the treatment with MSZRD led to increased serum GABA concentration, evident from a decreased Glu/GABA ratio. The levels of HPA axis-related hormones, including CORT, ACTH, and CRH, were also lower. MSZRD led to a remarkable lowering of serum Orexin-A content and hypothalamic OX2R expression in insomnia mice, moreover, it resulted in visible improvements in the hypothalamus's histopathological changes. These revelations suggest MSZRD's potential in relieving insomnia symptoms by regulating Orexin-A expression, balancing HPA axis homeostasis, and modulating neurotransmitter release.
