Upregulation of SIRT1 by Evodiamine activates PI3K/AKT pathway and blocks intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a major cause of a number of spinal diseases, resulting in serious public health problems. Evodiamine (Evo) is an indole quinazoline alkaloid extracted from Evodia rutaecarpa, which has antioxidant, anti­apoptosis and anti­inflammatory effects. The purpose of the present study was to investigate lipopolysaccharide (LPS)­induced IDD progression in human nucleus pulposus cells (NPCs) and its potential mechanism. The viability and apoptosis of NPCs were detected by Cell Counting Kit­8 (CCK­8) and TUNEL staining, respectively. Western blotting was used to detect the expression levels of proteins, cell transfection was performed to knockdown Sirtuin 1 (SIRT1) and the expression of tumor necrosis factor­alpha (TNF­α) and interleukin 6 (IL­6) was detected by enzyme­linked immunosorbent assay kits. The results showed that Evo effectively alleviated LPS­induced NPCs apoptosis and caspase­3 activation and Evo treatment reversed the upregulation of matrix metalloproteinase­13, as well as the downregulation of collagen type II (collagen II), Sry­type high­mobility­group box 9 and aggrecan and reduced the production of pro­inflammatory factors TNF­α and IL­6 in LPS­stimulated NPCs. In addition, treatment with Evo upregulated SIRT1 and activated the PI3K/Akt pathway, knockdown of SIRT1 inhibited the phosphorylation of Akt and PI3K in LPS­stimulated NPCs. In general, Evo upregulated SIRT1 and inhibited LPS­induced NPCs apoptosis, extracellular matrix degradation and inflammation by activating the PI3K/Akt pathway.