Xanthohumol protect cognitive performance in diabetic model rats by inhibiting protein kinase B/nuclear factor kappa-B pathway

Xanthohumol (XN, 2', 4', 4-trihydroxy-6'-methoxy-3'-prenylchalcone), a polyphenol chalcone from hops (Humulus lupulus), has received increasing attention due to its multiple pharmacologic activities. As an active component in beers, its presence has been suggested to be linked to the epidemiologic observation of the beneficial effect of regular beer drinking. But regarding cardiovascular and immunologic effects of polyphenols and ethanol, benefits of beer drinking in patients with diabetes were still in doubt. Diabetes was induced in male Sprague-Dawley rats by administering a high-fat diet and an intraperitoneal 30 mg/kg streptozotocin injection. The animals were treated orally with saline or XN at 50 mg/kg/d for 4 weeks. At the end of the treatment, hippocampus from different groups were collected for biochemical examination. In this study, we found XN inhibit phosphorylation of protein kinase B and nuclear factor kappa-B which was overactivated in diabetic rats, followed by decreased blood glucose and increased body weight. Additionally, XN treatment significantly increased freezing time in a fear memory test. In further research, we found XN increased synaptic plasticity and dendritic spine density, while decreased reactive oxygen species in hippocampus slices from diabetic rats. All these results indicate that XN might be a promising drug to treat diabetic encephalopathy.