Scutellarin Protects Against Mitochondrial ROS-Dependent NLRP3 Inflammasome Activation to Attenuate Intervertebral Disc Degeneration

Background: Intervertebral disc degeneration (IVDD) is a predominant reason for disc herniation, which is widespread all over the world. It is known that inflammatory responses, mitochondrial dysfunction and extracellular matrix degradation are involved in IVDD. Scutellarin, an active ingredient extracted from Erigeron breviscapus (Vaniot) Ha, Hand-Mazz, is reported to exhibit a therapeutic potential in several degenerative diseases through suppressing inflammation and regulating metabolism. However, whether scutellarin can improve IVDD remains unknown. Methods: 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. Moreover, activation of the NF-κB signaling pathway, MAPK signaling pathway and NLRP3 inflammasome was analyzed both in vitro and in vivo. Findings: Scutellarin attenuated the inflammatory reaction and retained the production of major IVD components both in vitro and in vivo. Mechanically, scutellarin reduced reactive oxygen species amount, alleviate d mitochondrial damage and decreased the expression levels of apoptosis-related biomarkers in stimulation of TNF-α. In addition, scutellarin antagonized the activation of NF-κB signaling pathway and p38 signaling pathway, and suppressed activity of NLRP3 inflammasome mediated by TNF-α. Interpretation: This study reveals that scutellarin protects against degeneration of nucleus pulposus cells, which might shed light on treatment of IVDD in the future. Funding: This study was financially supported by grants from the National Natural Science Foundation of China (81572191, 82073437, 82072478). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: This study was approved by the Medical Ethical Committee of Qilu Hospital of Shandong University.