Hyperoside ameliorates TNF‑α‑induced inflammation, ECM degradation and ER stress‑mediated apoptosis via the SIRT1/NF‑κB and Nrf2/ARE signaling pathways <em>in vitro</em>

Xie,Tian; Yuan,Jun; Mei,Ling; Li,Ping; Pan,Ruijie

doi:10.3892/mmr.2022.12776

Hyperoside ameliorates TNF‑α‑induced inflammation, ECM degradation and ER stress‑mediated apoptosis via the SIRT1/NF‑κB and Nrf2/ARE signaling pathways in vitro

Authors:
- Tian Xie
- Jun Yuan
- Ling Mei
- Ping Li
- Ruijie Pan
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Affiliations: Department of Orthopedics, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China, College of Acupuncture and Bone Injury, Hubei University of Chinese Medicine, Wuhan, Hubei 430061, P.R. China
Published online on: June 20, 2022 https://doi.org/10.3892/mmr.2022.12776
Article Number: 260
Copyright: © Xie 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 the main pathogenesis of numerous cases of chronic neck and back pain, and has become the leading cause of spinal‑related disability worldwide. Hyperoside is an active flavonoid glycoside that exhibits anti‑inflammation, anti‑oxidation and anti‑apoptosis effects. The purpose of the present study was to investigate the effect of hyperoside on tumor necrosis factor (TNF)‑α‑induced IDD progression in human nucleus pulposus cells (NPCs) and its potential mechanism. The activity and apoptosis of NPCs were detected by Cell Counting Kit‑8 and flow cytometry analyses, respectively. The expression of interleukin (IL)‑6 and IL‑1β was detected with ELISA kits. Western blotting was used to detect the expression levels of proteins. The results showed that hyperoside effectively alleviated TNF‑α‑induced NPC apoptosis, and hyperoside treatment inhibited the upregulation of inducible nitric oxide synthase, cyclooxygenase‑2, IL‑1β and IL‑6 in TNF‑α‑stimulated NPCs. Compared with the findings in the TNF‑α group, the intervention of hyperoside attenuated the upregulated expression of aggrecan and collagen II, and downregulated the expressions of matrix metalloproteinase (MMP) 3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 5. In addition, hyperoside upregulated sirtuin‑1 (SIRT1) and nuclear factor E2‑related factor 2 (Nrf2) protein expression, and inhibition of SIRT1 or Nrf2 signaling reversed the protective effect of hyperoside on TNF‑α‑induced NPCs. In summary, hyperoside ameliorated TNF‑α‑induced inflammation, extracellular matrix degradation, and endoplasmic reticulum stress‑mediated apoptosis, which may be associated with the regulation of the SIRT1/NF‑κB and Nrf2/antioxidant responsive element signaling pathways by hyperoside.

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