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, anti-apoptosis and anti-inflammatory 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 Kit-8 (CCK-8) 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 factor-alpha (TNF-alpha) and interleukin 6 (IL-6) was detected by enzyme-linked immunosorbent assay kits. The results showed that Evo effectively alleviated LPS-induced NPCs apoptosis and caspase-3 activation and Evo treatment reversed the upregulation of matrix metalloproteinase-13, as well as the downregulation of collagen type II (collagen II), Sry-type high-mobility-group box 9 and aggrecan and reduced the production of pro-inflammatory factors TNF-alpha and IL-6 in LPS-stimulated 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 LPS-stimulated NPCs. In general, Evo upregulated SIRT1 and inhibited LPS-induced NPCs apoptosis, extracellular matrix degradation and inflammation by activating the PI3K/Akt pathway.

Automated summary

In summary, Evo alleviates LPS-induced NPCs apoptosis and caspase-3 activation, reverses the ECM degradation, and reduces inflammation by upregulating SIRT1 and activating the PI3K/Akt pathway.