DMTHB ameliorates memory impairment in Alzheimer's disease mice through regulation of neuroinflammation

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Growing evidence suggested that AD is associated with neuroinflammation, characterized with the chronic activation of microglial cells and astrocytes along with the subsequent excessive generation of the proinflammatory molecules. This study aimed to investigate the effect and molecular mechanism of Demethylenetetrahydroberberine (DMTHB) on Alzheimer's disease (AD). Methods: AD mice model were made by intracranial injection of A beta(25-35). DMTHB (50 mg/kg or 150 mg/kg) was intragastrically administered every day for three weeks. Morris water maze (MWM) was applied to evaluate the capacity of learning and memory of mice. Pathological change and neuronal death were detected by HE staining Moreover, the expressions of NLRP3, ASC, Caspase 1, IL-6, IL-1 beta, TNF-alpha and Tau in the brain tissue were measured by qRT-PCR and western blot. Results: Our results showed that the cognition of AD mice was significantly improved by DMTHB administration. DMTHB inhibited the activation of the microglia and significantly reduced the expression of Iba-1 in the brains of AD mice. In addition, DMTHB effectively suppressed the activation of NLRP3 inflammasome induced by A beta(25-35). The results showed that the content of inflammatory cytokine (TNF-alpha, IL-1 beta and IL-6) in the brains of AD mice were down-regulated by DMTHB treatment. More importantly, DMTHB treatment significantly alleviated hippocampus neuron deformation and apoptosis. Conclusion: These results indicated that DMTHB could be a potential medicine against AD through regulation of neuroinflammation.