Albiflorin Attenuates Mood Disorders Under Neuropathic Pain State By Suppressing The Hippocampal NLRP3 Inflammasome Activation During Chronic Constriction Injury.

BACKGROUND Neuropathic pain (NP) is a multifaceted and ubiquitous disease across the globe. Mood disorders, such as anxiety and depression, are frequently observed in patients suffering from NP. Both NP and comorbid mood disorders seriously impacts the quality of life. Accumulated evidence shows that activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is involved in the neuroinflammatory pathogenesis of NP, anxiety, and depression. However, the role of the NLRP3 inflammasome in the pathological process of anxiety and depression under the NP state has not been fully described. Albiflorin (AF), a monoterpene glycoside, may be a potential regulator of the NLRP3 inflammasome, but it is not clear whether AF relates to NLRP3 inflammasome activation. METHODS We used a systematic pharmacological method to confirm whether the activation of the NLRP3 inflammasome in the hippocampus was involved in the development of NP associated with mood disorders, and whether AF could be an effective treatment for these symptoms. RESULTS The NLRP3 inflammasome contributed to the NP and comorbid anxiety and depression-like behaviors induced by chronic constriction injury of the sciatic nerve, and that AF may relieve these symptoms via inhibition of the NLRP3 inflammasome activity. Moreover, AF enhanced the translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and suppressed NF-κB activity in the hippocampus. CONCLUSIONS AF, as a potential therapeutic agent, might greatly improve the overall symptoms of NP.