Neuroprotective effect of, a flavonoid, sudachitin in mice stroke model.

A flavonoid, sudachitin, has been reported to show some beneficial health effects, including as an anti-inflammatory in LPS-stimulated macrophages, as well as improving glucose and lipid metabolism in mice fed a high-fat diet. In this study, we investigated the neuroprotective effect of sudachitin in the transient middle cerebral artery occlusion (tMCAO) mouse model. After daily pre-treatment of vehicle or sudachitin (5 or 50 mg/kg) for 14 days, mice (n = 76) were subjected to a sham operation or tMCAO for 45 min, and on the following days, they were treated daily with vehicle or sudachitin. The administration of sudachitin significantly reduced (p < 0.05) cerebral infarct volume and attenuated apoptosis, 5 days after tMCAO. Neurological impairment improved, the expression of an oxidative stress marker, 4-HNE, decreased, and the Sirt1/PGC-1α pathway was activated 5 days after tMCAO in the sudachitin-treated group. This is the first report to demonstrate the neuroprotective effect of sudachitin in cerebral ischemia/reperfusion injury mice model, probably by activating the Sirt1/PGC-1α axis. Sudachitin may be a promising supplement or therapeutic agent for reducing injury caused by ischemic strokes.

Injection of exogenous amyloid-ß oligomers aggravated cognitive deficits, and activated necroptosis, in APP23 transgenic mice.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the loss of synapses and neurons in the brain, and the accumulation of amyloid plaques. Aß oligomers (AßO) play a critical role in the pathogenesis of AD. Although there is increasing evidence to support the involvement of necroptosis in the pathogenesis of AD, the exact mechanism remains elusive. In the present study, we explored the effect of exogenous AßO injection on cell necroptosis and cognitive deficits in APP23 transgenic mice. We found that intrahippocampal injection of AßO accelerated the development of AD pathology and caused cognitive impairment in APP23 mice. Specifically, AßO injection significantly accelerated the accumulation of AßO and increased the expression level of phosphorylated-tau, and also induced necroptosis. Behavioral tests showed that AßO injection was associated with cognitive impairment. Furthermore, necroptosis induced by AßO injection occurred predominantly in microglia of the AD brain. We speculate that AßO increased necroptosis by activating microglia, resulting in cognitive deficits. Our results may aid in an understanding of the role played by AßO in AD from an alternative perspective and provide new ideas and evidence for necroptosis as a potential intervention and therapeutic target for AD.