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

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 Liu1,2 1Luzhou Longmatan District People’s Hospital, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Orthopedics and Traumatology, T...

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Main Authors: Wang X, Gao S, Zhou D, Cai W, Lv J, Wei Z, Song C, Shan X, Liu Z
Format: Article
Language:English
Published: Dove Medical Press 2025-05-01
Series:Journal of Inflammation Research
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Online Access:https://www.dovepress.com/unveiling-the-therapeutic-potential-of-baicalin-in-intervertebral-disc-peer-reviewed-fulltext-article-JIR
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author Wang X
Gao S
Zhou D
Cai W
Lv J
Wei Z
Song C
Shan X
Liu Z
author_facet Wang X
Gao S
Zhou D
Cai W
Lv J
Wei Z
Song C
Shan X
Liu Z
author_sort Wang X
collection DOAJ
description 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 Liu1,2 1Luzhou Longmatan District People’s Hospital, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China; 3Department of Orthopedics and Traumatology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu Province, 215009, People’s Republic of China; 4Gaoxian Traditional Chinese Medicine Hospital, Yibin, Sichuan Provience, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zongchao Liu, Luzhou Longmatan District People’s Hospital, No. 2 Guanyinbao Road, Shidong Town, Longmatan District, Luzhou, Sichuan, 646000, People’s Republic of China, Email lzcxnykdx@swmu.edu.cnBackground: 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: intervertebral disc degeneration, Baicalin, PANoptosis, bioinformatics, single-cell
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spelling doaj-art-41509bda4f9e4e199db19a6404fc843f2025-08-20T03:24:00ZengDove Medical PressJournal of Inflammation Research1178-70312025-05-01Volume 18Issue 169636981103421Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis InhibitionWang X0Gao S1Zhou DCai WLv J2Wei ZSong CShan XLiu Z3Department of Orthopedics and TraumatologyDepartment of Orthopedics and Traumatologyepartment of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine HospitalDepartment of Orthopedics and TraumatologyXiaoqiang 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 Liu1,2 1Luzhou Longmatan District People’s Hospital, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China; 3Department of Orthopedics and Traumatology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu Province, 215009, People’s Republic of China; 4Gaoxian Traditional Chinese Medicine Hospital, Yibin, Sichuan Provience, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zongchao Liu, Luzhou Longmatan District People’s Hospital, No. 2 Guanyinbao Road, Shidong Town, Longmatan District, Luzhou, Sichuan, 646000, People’s Republic of China, Email lzcxnykdx@swmu.edu.cnBackground: 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: intervertebral disc degeneration, Baicalin, PANoptosis, bioinformatics, single-cellhttps://www.dovepress.com/unveiling-the-therapeutic-potential-of-baicalin-in-intervertebral-disc-peer-reviewed-fulltext-article-JIRIntervertebral disc degenerationBaicalinPANoptosisBioinformaticsSingle-cell.
spellingShingle Wang X
Gao S
Zhou D
Cai W
Lv J
Wei Z
Song C
Shan X
Liu Z
Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis Inhibition
Journal of Inflammation Research
Intervertebral disc degeneration
Baicalin
PANoptosis
Bioinformatics
Single-cell.
title Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis Inhibition
title_full Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis Inhibition
title_fullStr Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis Inhibition
title_full_unstemmed Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis Inhibition
title_short Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis Inhibition
title_sort unveiling the therapeutic potential of baicalin in intervertebral disc degeneration integrative bulk and single cell transcriptome analysis with experimental validation of panoptosis inhibition
topic Intervertebral disc degeneration
Baicalin
PANoptosis
Bioinformatics
Single-cell.
url https://www.dovepress.com/unveiling-the-therapeutic-potential-of-baicalin-in-intervertebral-disc-peer-reviewed-fulltext-article-JIR
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