Emodin rescued hyperhomocysteinemia-induced dementia and Alzheimer's disease-like features in rats.
Từ khóa
trừu tượng
UNASSIGNED
Hyperhomocysteinemia (HHcy) is an independent risk factor for dementia, including Alzheimer's disease (AD). Lowering homocysteine levels with folic acid treatment with or without vitamin B12 was shown few clinical benefits on cognition.
UNASSIGNED
To verify the effect of emodin, a naturally active compound from Rheum officinale, on HHcy-induced dementia, rats were treated with homocysteine injection (HCY, 400 g/kg/day, 2 weeks) via vena caudalis. Afterwards, HCY rats with cognitive deficits were administered intragastric emodin at different concentrations, namely, 0 (HCY-E0), 20 (HCY-E20), 40 (HCY-E40) and 80 mg/kg/day (HCY-E80) for 2 weeks.
UNASSIGNED
β-amyloid (Aβ) overproduction, tau hyperphosphorylation and losses of neuron and synaptic proteins were detected in the hippocampi of HCY-E0 rats with cognitive deficits. HCY-E40 and HCY-E80 rats had better behavioural performances. Although it did not reduce the plasma homocysteine level, emodin (especially 80 mg/kg/day) reduced the levels of Aβ and tau phosphorylation, decreased the levels of β-site amyloid precursor protein-cleaving enzyme 1, and improved the activity of protein phosphatase 2A. In the hippocampi of HCY-E40 and HCY-E80 rats, the neuron numbers, levels of synaptic proteins and phosphorylation of the cAMP responsive element-binding protein at Ser133 were increased; in addition, depressed microglial activation and reduced levels of 5-lipoxygenase, interleukin-6 and tumour necrosis factor α were also observed. Lastly, HHcy-induced microangiopathic alterations, oxidative stress and elevated DNA methyltransferases 1 and 3 were rescued by emodin.
UNASSIGNED
Emodin represents a novel potential candidate agent for HHcy-induced dementia and AD-like features.
