Mechanisms of inhibition of nucleus pulposus cells pyroptosis through SDF1/CXCR4-NFkB-NLRP3 axis in the treatment of intervertebral disc degeneration by Duhuo Jisheng Decoction

Daru Guo; Kang Cheng; Chao Song; Fei Liu; Weiye Cai; Jingwen Chen; Yongliang Mei; Daqian Zhou; Silong Gao; Guoyou Wang; Zongchao Liu

doi:10.1016/j.intimp.2023.110844

Mechanisms of inhibition of nucleus pulposus cells pyroptosis through SDF1/CXCR4-NFkB-NLRP3 axis in the treatment of intervertebral disc degeneration by Duhuo Jisheng Decoction

Int Immunopharmacol. 2023 Nov;124(Pt A):110844. doi: 10.1016/j.intimp.2023.110844. Epub 2023 Aug 28.

Authors

Daru Guo¹, Kang Cheng¹, Chao Song¹, Fei Liu², Weiye Cai¹, Jingwen Chen¹, Yongliang Mei¹, Daqian Zhou¹, Silong Gao¹, Guoyou Wang³, Zongchao Liu⁴

Affiliations

¹ Department of Orthopedics and Traumatology (Trauma and Bone-setting), Laboratory of Integrated Chinese and Western Medicine for Orthopedic and Traumatic Diseases Prevention and Treatment, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China.
² Department of Orthopedics and Traumatology (Trauma and Bone-setting), Laboratory of Integrated Chinese and Western Medicine for Orthopedic and Traumatic Diseases Prevention and Treatment, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China; RuiKang Hospital affiliated to Guangxi University of Chinese Medicine, Nanning 530200, Guangxi, China.
³ Department of Orthopedics and Traumatology (Trauma and Bone-setting), Laboratory of Integrated Chinese and Western Medicine for Orthopedic and Traumatic Diseases Prevention and Treatment, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China. Electronic address: wang_guoyou1981@163.com.
⁴ Department of Orthopedics and Traumatology (Trauma and Bone-setting), Laboratory of Integrated Chinese and Western Medicine for Orthopedic and Traumatic Diseases Prevention and Treatment, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China; Luzhou Longmatan District People's Hospital, Luzhou 646000, Sichuan Province, China. Electronic address: lzcxnykdx@swmu.edu.cn.

PMID: 37647678
DOI: 10.1016/j.intimp.2023.110844

Abstract

Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain and the most common health problem in the world. Inflammasomes, which is mainly caused by NLRP3, mediated nucleus pulposus pyroptosis has been discovered to be strongly related to IVDD. In addition, Duhuo Jisheng Decoction (DHJSD) has anti-inflammatory and regulatory effects on NLRP3 inflammasome, but the molecular mechanism of whether DHJSD can regulate pyroptosis through NLRP3 to treat IVDD is unclear. In this study, we used a bioinformatics way to discover the molecular mechanism of DHJSD regulation of pyroptosis in IVDD, and validated our predictions through vitro and vivo experiments. Through bioinformatics, we found that NLRP3, GSDMD, IL-1βand other hub proteins of pyroptosis were highly expressed in IVDD SD rats, and network pharmacology discovered that DHJSD may control cellular senescence, apoptosis, and pyroptosis in order to treat IVDD. Additional findings demonstrated that DHJSD could successfully treat IVDD brought on by imaging and histomorphological analysis. Western blot showed that NLRP3, a key protein of pyroptosis, was elevated in rat degenerated nucleus pulposus tissue and lipopolysaccharide-treated Nucleus pulposus Cells (NPCs), and that DHJSD intervention was effective in reducing LPS-induced inflammatory responses and further suppressing the expression of pyroptosis related proteins to improve IVDD. The specific mechanism is that DHJSD inhibits NPCs pyroptosis via the SDF-1/CXCR4-NF-kB-NLRP3 axis. In conclusion, we revealed the intrinsic mechanism of DHJSD regulation of NPCs pyroptosis to improve IVDD and its intrinsic value for IVDD treatment.

Keywords: Bioinformatics; Duhuo Jisheng Decoction; Intervertebral disc degeneration; Network pharmacology; Nucleus pulposus Cells; Pyroptosis.