Ganoderic Acid A To Alleviate Neuroinflammation of Alzheimer’s Disease in Mice by Regulating the Imbalance of the Th17/Tregs Axis

Ganoderic acid A (GAA) is a kind of lanostane-type triterpenoid isolated from Ganoderma lucidum. Imbalance of the Th17/Tregs axis exists in the progress of neuroinflammation of Alzheimer's disease (AD). In this study, the alleviating neuroinflammatory effect of GAA on d-galactose mice was studied from the aspect of regulating the imbalance of the Th17/Tregs axis. The Morris water maze test was used to evaluate the cognitive ability of AD mice. Flow cytometry was used to detect the percentages of IL-17A, IL-17F, IL-21, IL-22, and CD4+CD25+Foxp3+ in peripheral blood. Transmission electron microscopy was used to assess the cerebral mitochondrial ultrastructure. Metabolomic analysis based on gas chromatography-mass spectrometry was used to evaluate the mitochondrial dysfunction metabolism. Western blot analysis was used to detect the protein expressions of cytokines secreted by Th17 cells and Treg cells in the brain. As the results show, GAA has an alleviating neuroinflammatory effect on AD mice via regulating the imbalance of the Th17/Tregs axis. The potential mechanism was related to inhibition of the JAK/STAT signaling pathway induced by Th17 cells and enhancement of the mitochondrial oxidative phosphorylation by regulating Treg cells, thereby improving mitochondrial dysfunction of AD mice.