Chaihu-Jia-Longgu-Muli Decoction Alleviates Radiation-Induced Insomnia Via Suppressing NF-κB/MAPK Signaling Pathways

Background Insomnia is a common and burdensome sleep disorder, especially in cancer patients undergoing radiotherapy. Although Chaihu Jia Longgu Muli Decoction (CLMD) has been implicated in neuroinflammatory regulation, its role in radiation-induced sleep disruption remains unknown. This study investigates the neuroprotective effects of CLMD against radiation-induced neuronal injury and its molecular basis. Methods SH-SY5Y cells were exposed to 4 Gy X-ray irradiation to establish an in vitro radiation injury model. Cellular functions (viability and apoptosis), oxidative stress markers (ROS, MDA, GSH, TAS), inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10), and NF-κB/ERK signaling pathway proteins were assessed using standard biochemical and molecular biology techniques. Result X-ray radiation markedly elevated the relative levels of p-p65/p65 and p-ERK/ERK (P < 0.001 for 4 Gy). This irradiation increased reactive oxygen species and malondialdehyde levels alongside decreased glutathione and total antioxidant status (all P < 0.001). At the same time, there was an increase in the levels of IL-1β, IL-6, and TNF-α, while IL-10 showed a decrease (all P < 0.001). CLMD treatment (25, 50, and 75 mg/L) suppressed radiation-induced NF-κB (p-p65) and ERK MAPK activation, reduced oxidative stress and inflammatory responses, restored cell viability, and inhibited apoptosis in a dose-dependent manner (all P < 0.001). The protective effects of the highest CLMD dose (75 mg/L) were comparable to those of the positive control daridorexant (10 μM). Conclusion CLMD mitigates neuronal injury induced by radiation through the inhibition of the NF-κB (p-p65) and ERK MAPK signaling pathway, leading to a reduction in oxidative stress and inflammatory responses. These findings providing mechanistic support for its potential role in managing insomnia and other neuropsychiatric disorders of radiotherapy, while acknowledging that behavioral sleep outcomes were not directly assessed in this study. The application of CLMD in clinical practice will require further validation through animal studies and clinical trials.