Bergaptol Alleviates LPS-Induced Neuroinflammation, Neurological Damage and Cognitive Impairment via Regulating the JAK2/STAT3/p65 Pathway

Jianbing Wu,1,* Jie Zhang,1,* Qiangli Xie,2 Xiaohuan He,3 Zhangchao Guo,1 Bo Zheng,4 Sisong Wang,5 Qiumei Yang,6 Chunfu Du1 1Department of Neurosurgery, Ya’an People’s Hospital, Ya’an, 625000, People’s Republic of China; 2Department of Cardiovascular Medicine, Chengdu Qingbaijiang District People’s Hospital, Chengdu, 610300, People’s Republic of China; 3Department of the Fifth Dispatched Outpatient, The General Hospital of Western Theater Command, Chengdu, 610083, People’s Republic of China; 4Department of Neurology, Ya’an People’s Hospital, Ya’an, 625000, People’s Republic of China; 5Department of Neurosurgery, the Chengdu 363 Affiliated Hospital of Southwest Medical University, Chengdu, 610041, People’s Republic of China; 6Department of Geriatrics, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunfu Du, Department of Neurosurgery, Ya’an People’s Hospital, 358 Chenghou Road, Ya’an, Sichuan, 625000, People’s Republic of China, Tel +86-835-2862065, Email 1012036559@qq.comPurpose: Neuroinflammation is considered a critical pathological process in various central nervous system (CNS) diseases and is closely related to neuronal death and dysfunction. Bergaptol is a natural 5-hydroxyfurocoumarin found in lemon, bergamot and other plants. Some studies have confirmed its anti-cancer, anti-inflammatory and anti-atherogenic functions, indicating that it may have significant medicinal value. In this study, we investigated the potential effect of Bergaptol in vitro and in vivo neuroinflammatory models.Methods: Mice were injected with LPS (40 μg/kg) into the hippocampal CA1 region and then injected intraperitoneally with Bergaptol (10, 20 and 40 mg/kg) once a day for two weeks. In addition, to verify the effect of Bergaptol on BV2 cells, Bergaptol with different concentrations (5, 10 and 20 μg/mL) was firstly incubated for 1 hour, then LPS with a concentration of 1 μg/mL was added and incubated for 23 hours.Results: Bergaptol treatment significantly improved the cognitive impairment induced by LPS. In addition, Bergaptol significantly inhibited the reduction of dendritic spines and the mRNA level of inflammatory factors (TNF-α, IL-6 and IL-1β) in hippocampal induced by LPS. In vitro, Bergaptol inhibited the production of TNF-α, IL-6 and IL-1β from LPS-treated BV-2 cells. In addition, Bergaptol treatment significantly reduced the phosphorylation levels of JAK2, STAT3 and p65 in LPS-stimulated BV-2 cells.Conclusion: In conclusion, our results suggest that Bergaptol alleviates LPS-induced neuroinflammation, neurological damage and cognitive impairment by regulating the JAK2/STAT3/P65 pathway, suggesting that Bergaptol is a promising neuroprotective agent.Keywords: Bergaptol, neuroinflammation, LPS, JAK2/STAT3/p65