Scutellarin Protects Against Mitochondrial Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation to Attenuate Intervertebral Disc Degeneration

Zihao Wang; Pengfei Zhang; Yunpeng Zhao; Feiran Yu; Shaoyi Wang; Kaiwen Liu; Xiang Cheng; Jie Shi; Qiting He; Yanni Xia; Lei Cheng

doi:10.3389/fbioe.2022.883118

Scutellarin Protects Against Mitochondrial Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation to Attenuate Intervertebral Disc Degeneration

Front Bioeng Biotechnol. 2022 Aug 11:10:883118. doi: 10.3389/fbioe.2022.883118. eCollection 2022.

Authors

Zihao Wang^{1

2}, Pengfei Zhang^{1

2

3}, Yunpeng Zhao¹, Feiran Yu⁴, Shaoyi Wang^{1

2}, Kaiwen Liu^{1

2}, Xiang Cheng², Jie Shi^{1

2}, Qiting He^{1

2}, Yanni Xia³, Lei Cheng¹

Affiliations

¹ Department of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Cheeloo College of Medicine, Shandong University, Jinan, China.
³ Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ School of Medical Imaging, Weifang Medical University, Weifang, China.

Abstract

Intervertebral disc degeneration (IVDD) is a predominant cause of disc herniation and is widespread worldwide. Inflammatory responses, mitochondrial dysfunction, and extracellular matrix degradation are known to be involved in IVDD. Scutellarin, an active ingredient extracted from Erigeron breviscapus (Vaniot) Ha, Hand-Mazz, is reported to exhibit therapeutic potential in several degenerative diseases by suppressing inflammation and regulating metabolism. However, whether scutellarin can improve IVDD remains unknown. Human primary nucleus pulposus cells (HNPCs) were cultured and stimulated with TNF-α in the presence or absence of scutellarin. Furthermore, a rat needle puncture model was established, and scutellarin was injected into the IVD to verify its protective function against IVDD. Scutellarin attenuated the inflammatory reaction and retained the production of major IVD components both in vitro and in vivo. Mechanistically, scutellarin reduced the amount of reactive oxygen species (ROS), alleviated mitochondrial damage, and decreased the expression levels of apoptosis-related biomarkers upon stimulation with TNF-α. In addition, scutellarin antagonized the activation of the nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway and suppressed the activity of the NLRP3 inflammasome mediated by TNF-α. This study reveals that scutellarin protects against degeneration of nucleus pulposus cells, which might shed light on treatment of IVDD in the future.

Keywords: NF-κB signaling 3 pathway; NLRP3; intervertebral disc degeneration; mitochondrial ROS; scutellarin.