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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.

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Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy, and shows clinical and genetic heterogeneity. Mutations in C1orf194 encoding a Ca2+ regulator in neurons and Schwann cells have been reported previously by us to cause CMT disease. In here, we further investigated the function and pathogenic mechanism of C1or194 by generating C1orf194 knockout (KO) mice. Homozygous mutants of C1orf194 mice exhibited incomplete embryonic lethality, characterized by differentiation abnormalities and stillbirth on embryonic days 7.5 to 15.5. Heterozygous and surviving homozygous C1orf194 KO mice developed motor and sensory defects at the age of 4 months. Electrophysiologic recordings showed decreased compound muscle action potential and motor nerve conduction velocity in the sciatic nerve of C1orf194-deficient mice as a pathologic feature of dominant intermediate-type CMT. Transmission electron microscopy analysis revealed demyelination and axonal atrophy in the sciatic nerve as well as swelling and loss of mitochondrial matrix and other abnormalities in axons and Schwann cells. A histopathologic examination showed a loss of motor neurons in the anterior horn of the spinal cord and muscle atrophy. Shorter internodal length between nodes of Ranvier and Schmidt-Lanterman incisures (SLIs) were detected in the sciatic nerve of affected animals. These results indicate that C1orf194 KO mice can serve as an animal model of CMT with a severe dominant intermediate CMT phenotype that can be used investigate the molecular mechanisms of the disease and evaluate the efficacy of therapeutic strategies.

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