NDLI: Anemonin reduces hydrogen peroxide-induced oxidative stress, inflammation and extracellular matrix degradation in nucleus pulposus cells by regulating NOX4/NF-κB signaling pathway

Content Provider	Springer Nature : BioMed Central
Author	Ma, Zhijia Yu, Pengfei Li, Xiaochun Dai, Feng Jiang, Hong Liu, Jintao
Abstract	Background Excessive oxidative stress plays a critical role in the progression of various diseases, including intervertebral disk degeneration (IVDD). Recent studies have found that anemonin (ANE) possesses antioxidant and anti-inflammatory effects. However, the role of ANE in IVDD is still unclear. Therefore, this study investigated the effect and mechanism of ANE on H2O2 induced degeneration of nucleus pulposus cells (NPCs). Methods NPCs were pretreated with ANE, and then treated with H2O2. NOX4 was upregulated by transfection of pcDNA-NOX4 into NPCs. Cytotoxicity was detected by MTT, oxidative stress-related indicators and inflammatory factors were measured by ELISA, mRNA expression was assessed by RT-PCR, and protein expression was tested by western blot. Results ANE attenuated H2O2-induced inhibition of NPCs activity. H2O2 enhanced oxidative stress, namely, increased ROS and MDA levels and decreased SOD level. However, these were suppressed and pretreated by ANE. ANE treatment repressed the expression of inflammatory factors (IL-6, IL-1β and TNF-α) in H2O2-induced NPCs. ANE treatment also prevented the degradation of extracellular matrix induced by H2O2, showing the downregulation of MMP-3, 13 and ADAMTS-4, 5 and the upregulation of collagen II. NOX4 is a key factor regulating oxidative stress. Our study confirmed that ANE could restrain NOX4 and p-NF-κB. In addition, overexpression of NOX4 counteracted the antioxidant and anti-inflammatory activities of ANE in H2O2-induced NPCs, and the inhibition of the degradation of extracellular matrix induced by ANE was also reversed by overexpression of NOX4. Conclusion ANE repressed oxidative stress, inflammation and extracellular matrix degradation in H2O2-induced NPCs by inhibiting NOX4/NF-κB pathway. Our study indicated that ANE might be a candidate drug for the treatment of IVDD.
Related Links	https://josr-online.biomedcentral.com/counter/pdf/10.1186/s13018-023-03679-8.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13018-023-03679-8
Journal	Journal of Orthopaedic Surgery and Research
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2023-03-11
Access Restriction	Open
Subject Keyword	Orthopedics Surgical Orthopedics Anemonin Oxidative stress Inflammation Extracellular matrix Nucleus pulposus cells
Content Type	Text
Resource Type	Article
Subject	Surgery Orthopedics and Sports Medicine
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3/2023

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