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

Kuai,Jianbo; Zhang,Na

doi:10.3892/mmr.2022.12781

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

Authors:
- Jianbo Kuai
- Na Zhang
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Affiliations: Department of Orthopedics, Jianhu County People's Hospital, Yancheng, Jiangsu 224700, P.R. China, Department of Orthopedics, Fengfeng General Hospital, North China Medical Health Group, Handan, Hebei 056200, P.R. China
Published online on: June 24, 2022 https://doi.org/10.3892/mmr.2022.12781
Article Number: 265
Copyright: © Kuai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑α) 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‑α 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.

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