Details

Autor(en) / Beteiligte

• Zhang, Li
• Wong, Ling Rong
• Wong, Peiyan
• Shen, Wanxiang
• Yang, Shili
• Huang, Lizhen
• Lim, Yun-An
• Ho, Paul Chi-Lui

Titel

Chronic treatment with baicalein alleviates behavioural disorders and improves cerebral blood flow via reverting metabolic abnormalities in a J20 transgenic mouse model of Alzheimer's disease

Ist Teil von

• Brain, behavior, & immunity. Health, 2023-03, Vol.28, p.100599-100599, Article 100599

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Baicalein (BE) has both antioxidant and anti-inflammatory effects. It has also been reported able to improve cerebral blood circulation in brain ischemic injury. However, its chronic efficacy and metabolomics in Alzheimer's disease (AD) remain unknown. In this study, BE at 80 mg/kg was administrated through the oral route in J20 AD transgenic mice aged from aged 4 months to aged 10 months. Metabolic- and neurobehavioural phenotyping was done before and after 6 months' treatment to evaluate the drug efficacy and the relevant mechanisms. Meanwhile, molecular docking was used to study the binding affinity of BE and poly (ADP-ribose) polymerase-1 (PARP-1) which is related to neuronal injury. The open field test showed that BE could suppress hyperactivity in J20 mice and increase the frequency of the target quadrant crossing in the Morris Water Maze test. More importantly, BE restored cerebral blood flow back to the normal level after the chronic treatment. A 1H NMR-based metabolomics study showed that BE treatment could restore the tricarboxylic acid cycle in plasma. And such a treatment could suppress oxidative stress, inhibit neuroinflammation, alleviate mitochondrial dysfunction, improve neurotransmission, and restore amino homeostasis via starch and sucrose metabolism and glycolipid metabolism in the cortex and hippocampus, which could affect the behavioural and cerebral blood flow. These findings showed that BE is a potential therapeutic agent for AD. •Chronic baicalein treatment reverts cognitive impairments and restores cerebral blood flow in Alzheimer disease (AD) mice.•Metabolomics in plasma and in brain of AD mice before/after treatment reveal mechanisms of action of baicalein.•Molecular docking indicates binding of baicalein to PARP-1 protein as one of its mechanisms of action.