Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis Inhibition

  • J Inflamm Res. 2025 May 30:18:6963-6981. doi: 10.2147/JIR.S519179.
Xiaoqiang Wang  #  1  2 ,  Silong Gao  #  2 ,  Daqian Zhou  2 ,  Weiye Cai  3 ,  Jiale Lv  2 ,  Zhangchao Wei  2 ,  Chao Song  2 ,  Xubin Shan  4 ,  Zongchao Liu  1  2
Affiliations
  • 1. Luzhou Longmatan District People's Hospital, Luzhou, Sichuan Province, People's Republic of China.
  • 2. Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, People's Republic of China.
  • 3. Department of Orthopedics and Traumatology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu Province, 215009, People's Republic of China.
  • 4. Gaoxian Traditional Chinese Medicine Hospital, Yibin, Sichuan Provience, People's Republic of China.
  • # Contributed equally.
PMID: 40463856 DOI: 10.2147/JIR.S519179
Abstract

Background: Programmed cell death (PCD), including Pyroptosis, Apoptosis, and Necroptosis, plays a critical role in the pathogenesis of intervertebral disc degeneration (IVDD). PANoptosis, a recently identified form of PCD integrating Pyroptosis, Apoptosis, and Necroptosis, may represent a more comprehensive target for therapeutic intervention in IVDD.

Objective: To explore the role of PANoptosis in IVDD and investigate the therapeutic potential and underlying mechanism of baicalin in regulating PANoptosis to alleviate disc degeneration.

Methods: We performed integrative analyses of bulk transcriptomic datasets (GSE167199, GSE245147, GSE266883) and a single-cell RNA-seq dataset (GSE244889) to identify PANoptosis-related genes involved in IVDD. The expression and function of key genes were validated using clinical samples, an IL-1β-induced NPC degeneration model in vitro, and a puncture-induced rat IVDD model in vivo treated with baicalin.

Results: Five core PANoptosis-related genes (FOS, CASP1, H1-2, BCL2L11, and H2AC6) were significantly upregulated in degenerated discs. Baicalin treatment effectively downregulated these genes at both mRNA and protein levels. Moreover, baicalin alleviated IL-1β-induced cell death in NPCs and improved histological features in the rat IVDD model.

Conclusion: Our findings reveal a critical role of PANoptosis in IVDD progression and demonstrate that baicalin alleviates disc degeneration by inhibiting PANoptosis. This study provides novel insights into PANoptosis as a promising therapeutic target for IVDD.

Keywords
Baicalin; PANoptosis; bioinformatics; intervertebral disc degeneration; single-cell.
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