Jiao-tai-wan Improves Cognitive Impairment by Regulating Nrf2/ARE/HO-1 Signaling Pathway in APP/PS1 mice

Backgroud Alzheimer's disease (AD) is a chronic, progressive, and destructive neurodegenerative disorder that severely affects human memory, intelligence, and behavioral abilities. Jiao Tai Wan (JTW) is a classic formula composed of two traditional Chinese medicines, coptis chinensis (CC) and cinnamon (CIN), the ratio of CC and CIN is 10:1. JTW has the effects of promoting cognitive function, and improving learning and memory function. But the specific mechanism has not been systematically studied. Method: We conducted Morris water maze and Y-maze behavioral tests, polymerase chain reaction (PCR), assay kit and ELISA, nissl's staining, and western blotting to verified the improvement of cognitive function of JTW on APP/PS1 mice. Result: Through behavioral experiments, JTW can improved the learning and spatial exploration abilities of APP/PS1 mice. Nissl’s staining and PCR detection of BDNF, NGF, and SYP showed that JTW can improved neurodegenerative lesions in APP/PS1 mice. By detecting the activities of A β 1-40, A β 1-42, α - secretase, β - secretase, and γ - secretase, as well as cholinergic labeling enzymes of Ach, AchE, and ChAT activities showed that JTW improved cerebral amyloidosis and cholinergic nervous system in APP/PS1 model mice. The detection of inflammatory factors and oxidative stress indicators revealed that JTW can inhibited the activity of inflammatory factors and oxidative stress. Western Blotting was used to detect the Nrf2/ARE/HO-1 pathway, and the result showed that JTW can regulate the Nrf2/ARE/HO-1 pathway to improving cognitive function of APP/PS1 mice. Conclusion: JTW enhanced the activity of Nrf2, regulated the Nrf2/ARE/HO-1 pathway, increased the activity of nerve growth factors, improved the cholinergic nervous system, inhibited inflammatory factors and oxidative stress, and ameliorated cognitive dysfunction in APP/PS1 mice.