Galangin decreases p‑tau, Aβ42 and β‑secretase levels, and suppresses autophagy in okadaic acid‑induced PC12 cells via an Akt/GSK3β/mTOR signaling‑dependent mechanism

: Okadaic acid (OA)‑induced neurotoxicity may be considered a novel tool used to study Alzheimer's disease (AD) pathology, and may be helpful in the development of a novel therapeutic approach. It has been reported that galangin inhibits β‑site amyloid precursor protein‑cleaving enzyme 1 expression, which is a key enzyme for amyloid β (Aβ) generation and is a potential drug candidate for AD therapy. However, further studies are required to confirm its neuroprotective effects in other AD models. The present study aimed to explore the neuroprotective effects of galangin on OA‑induced neurotoxicity in PC12 cells. The cells were divided into the following groups: Control group, model group (175 nM OA for 48 h) and galangin groups (0.25, 0.5 and 1 µg/ml). Beclin‑1, phosphorylated (p)‑protein kinase B (Akt), p‑glycogen synthase kinase (GSK)3β and p‑mechanistic target of rapamycin (mTOR) expression was also measured in the following PC12 cell groups: Control group, model group, 3‑methyladenine group (5 nM), rapamycin group (100 nM) and galangin group (1 µg/ml). The levels of β‑secretase, Aβ42 and p‑tau were detected by ELISA, Beclin‑1 expression was examined by immunohistochemistry and the protein expression levels of p‑Akt, p‑mTOR p‑GSK3β, and Beclin‑1 were detected by western blotting. Galangin treatment enhanced cell viability in cells treated with OA, and decreased β‑secretase, Aβ42 and p‑tau levels. In addition, it suppressed Beclin‑1 and p‑GSK3β expression, but promoted p‑Akt and p‑mTOR expression by regulating the Akt/GSK3β/mTOR pathway. These results indicated that galangin protected PC12 cells from OA‑induced cytotoxicity and inhibited autophagy via the Akt/GSK3β/mTOR pathway, thus suggesting that it may be considered a potential therapeutic agent for AD.