Lipoic acid alleviates LPS‑evoked PC12 cell damage by targeting p53 and inactivating the NF‑κB pathway

Abstract

Lipoic acid (LA) exerts several beneficial effects including anti‑inflammatory and antioxidant activity. This research aims to explore the function and mechanisms of LA on lipopolysaccharide (LPS)‑induced PC12 cells. PC12 cells stimulated by LPS were used to mimic an in vitro inflammatory model of Parkinson’s disease. Cell toxicity was determined by a cell counting kit‑8 assay after various treatments. The concentrations of tumor necrosis factor (TNF-α), interleukin (IL)‑1β and IL‑6 were analyzed by an ELISA kit. The effects of LA on\r\ncell apoptosis and cell cycle were measured by flow cytometry. The levels of α‑syn, Nurr1 and tyrosine hydroxylase (TH) were tested by immunocytochemistry and ELISA kits. Western blotting assays were used to measure the expression of NF‑κB pathway‑related proteins. In PC12 cells, 100 μmol/mL LA effectively attenuated the upregulation of TNF‑α, IL‑1β and IL‑6 triggered by LPS; inhibited the increase of cell apoptosis; and relieved the cell cycle arrest induced. Additionally, the increase in α‑syn and the decrease in Nurr1 and TH triggered by LPS were reversed by 100 μmol/mL LA. We also found that the elevated expression of p53 in LPS‑induced PC12 cells was suppressed by LA. Significantly, knockdown of p53 enhanced the ameliorative effect of LA on LPS‑triggered PC12 cell damage. The increase in levels of p‑p65 NF‑κB and p‑IκBα triggered by LPS were suppressed by LA and si‑p53 combination treatment. The results indicate that LA can attenuate LPS‑triggered inflammation and apoptosis in PC12 cells by targeting the p53/NF‑κB pathway.\r\nThese findings provide a theoretical basis for the future treatment of inflammation in Parkinson’s disease.