Abstract: The AD in vitro model was established by using D-galactose synergistically with Aβ1-42 to induce the damage of HT-22 cells. The purpose of this study was to investigate the role of PPARγ/PGC-1α signaling pathway in D-galactose synergistic Aβ1-42 induced HT-22 cell injury and the intervention mechanism of tenuifolin. MTT assay was used to detect cell viability; Trypan blue dye exclusion assay was used to detect cell death rate; β-galactosidase staining was used to detect cell aging; Mito-Tracker fluorescent labeling to observe mitochondrial damage; Rhodamine 123 staining was applied to detect changes in mitochondrial membrane potential by flow cytometry; Colorimetry was used to detect changes in ultra-trace total ATPase content; Western Blotting was used to detect PPARγ, PGC-1α, COX-2 and NF-κB protein expression. The content of inflammatory factors such as TNF-α, IL-6 were detected by ELISA method. The results showed that compared with the model group, tenuifolin (10, 20, 40 μmol/L) could significantly improve the survival rate of HT-22 cells induced by D-galactose synergistically with Aβ1-42, and reduce the positive rate of β-galactosidase, increase intracellular ATPase activity, prevent the decrease of mitochondrial membrane potential, inhibit the increase of inflammatory factors such as TNF-α, IL-6 levels, down-regulate the expression of NF-κB and COX-2 and up-regulate the expression of PPARγ, PGC-1α in HT-22 cells. The above results suggest that tenuifolin has a protective effect on HT-22 cells damaged by D-galactose synergistically with Aβ1-42 within a certain dose range, and the protective mechanism may be related to up-regulating PPARγ/PGC-1α signaling pathway, enhancing mitochondrial energy metabolism and blocking the inflammatory response.

Key words: tenuifolin, Aβ1-42, mitochondrial energy metabolism, HT-22 cells, PPARγ/PGC-1α signaling pathway