Chlorogenic acid improves SPS-induced PTSD-like behaviors in rats by regulating the crosstalk between Nrf2 and NF-κB...

Post-traumatic stress disorder (PTSD) is a long-term delayed mental disorder caused by sudden, threatening or catastrophic life events. Chlorogenic acid (CGA) is a polyphenolic acid rich in Eucommia ulmoides and other plants with potential neuroprotective effects, effectively enhances learning and memory, and exerts a beneficial impact on improving mood and attention. However, the effects and mechanisms of CGA on PTSD-like behaviors remain uncertain. This study is to explore the effects and mechanisms of CGA on PTSD by using network pharmacology analysis, molecular docking and experimental validation, and try to provide new strategies for the treatment of PTSD. The results indicated that 9 core targets with a strong binding affinity with CGA were screened out, and they were mainly enriched in apoptosis, inflammation, and oxidative stress. The followed vivo experiments indicated that CGA could alleviate single prolonged stress (SPS)-induced PTSD-like behaviors, and improve hippocampal pathological damage, apoptosis and synaptic plasticity through antioxidant and anti-inflammatory effects by regulating Nrf2 and NF-κB pathways. Thus, CGA may inhibit hippocampal neuronal apoptosis, reduce neuroinflammatory and oxdiative stress response, and enhance hippocampal synaptic plasticity through regulating the crosstalk between Nrf2 and NF-κB signaling pathway, thereby improving SPS-induced PTSD-like behaviors.