PMID:
CNS Neurol Disord Drug Targets. 2019 Aug 7. Epub 2019 Aug 7. PMID: 31389320
Abstract Title:
Formononetin ameliorates cognitive disorder via PGC-1α pathway in neuroinflammation conditions in high-fat diet-induced mice.
Abstract:
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in many modern societies. Previous studies have shown that neuroinflammation is one of the pathogenesis of AD. Formononetin (FN), an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. The present study focused on the protective activities of FN on a high-fat diet (HFD)-induced cognitive decline and explored the underlying mechanisms. We found that FN (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol (TC) and triglyceride (TG) in HFD-induced mice. Meanwhile, we observed HFD significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas FN reversed this effect. Additionally, FN markedly reduced the levels of inflammation cytokines IL-1β and TNF-α in HFD-induced mice. The mechanism study showed that FN suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of HFD-induced mice. Taken together, our results showed that FN could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.
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