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ORIGINAL RESEARCH article
Front. Med.
Sec. Pathology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1593317
This article is part of the Research TopicRegulation of intervertebral disc homeostasis and the pathological or pathophysiological alterations under various harmful stimuli during aging processView all 4 articles
Chrysin Attenuates Intervertebral Disc Degeneration via Dual Inhibition of Matrix Metalloproteinases and Senescence: Integrated Network Pharmacology, Molecular Docking, and Experimental Validation
Provisionally accepted
zeyu Pang1,2
Junxian Hu1,2
Chen Zhao1,2Xiaoxiao Li1,2Yibo Zhu1,2
Xiangwei Li1,2
Yiyang Wang1,2*
Qiang Zhou1,2*
Pei Li1,2*- 1Department of Orthopedics, Third Affiliated Hospital of Chongqing Medical University, Chongging, Sichuan Province, China
- 2Tissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
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degeneration(DDD)caused by nucleus pulposus cell(NPCs)senescence, oxidative stress, and extracellular matrix(ECM) degradation is one of the leading causes of chronic low back pain, yet effective treatments remain elusive. This study investigated the potential of chrysin, a natural flavonoid with antioxidant and anti-inflammatory properties, to alleviate NPCs aging and ECM dysregulation. Through network pharmacology, researchers identified 89 overlapping targets between chrysin and DDD, including MMP2, MMP9, and TGFB1. Enrichment analyses revealed key pathways in cancer, such as JAK-STAT signaling, efflux cells, and central carbon metabolism. Molecular docking showed that chrysin has a strong binding affinity for MMP2(-8.4 kcal/mol) and MMP9(-8.2 kcal/mol), key enzymes for ECM degradation. Molecular dynamics simulations demonstrated that the Chrysin-MMP-9 and Chrysin-MMP-2 complexes exhibited favorable dynamic properties.Experimental validation in H₂O₂-induced senescent NPCs confirmed the protective effects of chrysin: pretreatment with chrysin(1 μM) significantly reduced senescence-associated β-galactosidase activity and inhibited MMP2/9 mRNA expression while restoring collagen II and aggrecan levels. In addition, Chrysin attenuated oxidative stress-mediated ECM damage, which was consistent with network predictions. These findings highlight the dual ability of Chrysin to inhibit MMP activity and combat aging, making it a promising multi-targeted therapeutic candidate for the treatment of DDD. This study combines bioinformatics with experimental modeling to mechanistically reveal the anti-aging mechanism of Chrysin.
Keywords: Chrysin, Network Pharmacology, Intervertebral Disc Degeneration, Aging and Degeneration, molecular docking, molecular dynamics simulations
Received: 13 Mar 2025; Accepted: 17 Apr 2025.
Copyright: © 2025 Pang, Hu, Zhao, Li, Zhu, Li, Wang, Zhou and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yiyang Wang, Department of Orthopedics, Third Affiliated Hospital of Chongqing Medical University, Chongging, 401120, Sichuan Province, China
Qiang Zhou, Department of Orthopedics, Third Affiliated Hospital of Chongqing Medical University, Chongging, 401120, Sichuan Province, China
Pei Li, Department of Orthopedics, Third Affiliated Hospital of Chongqing Medical University, Chongging, 401120, Sichuan Province, China
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