Gamma-oryzanol alleviates intervertebral disc degeneration development by intercepting the IL-1β/NLRP3 inflammasome positive cycle.

Animals Inflammasomes / metabolism Interleukin-1beta / metabolism Intervertebral Disc Degeneration / drug therapy NLR Family, Pyrin Domain-Containing 3 Protein / metabolism Nucleus Pulposus / metabolism Phenylpropionates Rats
Gamma-oryzanol Intervertebral disc degeneration NF-κB NLRP3 inflammasome Nucleus pulposus

Journal

Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794

Informations de publication

Date de publication:
20 Jul 2022
Historique:
received: 22 02 2022
revised: 04 05 2022
accepted: 14 05 2022
pubmed: 7 6 2022
medline: 15 6 2022
entrez: 6 6 2022
Statut: ppublish

Résumé

Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1β/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown. This study aims to validate the role of Ory in IVDD and explore the potential mechanism. Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory. The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1β-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels. Ory treatment inhibited IL-1β-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1β/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development. Our results support the potential application of Ory as a therapeutic compound for IVDD.

Sections du résumé

BACKGROUND BACKGROUND
Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1β/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown.
PURPOSE OBJECTIVE
This study aims to validate the role of Ory in IVDD and explore the potential mechanism.
STUDY DESIGN METHODS
Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory.
METHOD METHODS
The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1β-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels.
RESULTS RESULTS
Ory treatment inhibited IL-1β-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1β/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development.
CONCLUSION CONCLUSIONS
Our results support the potential application of Ory as a therapeutic compound for IVDD.

Identifiants

DOI: 10.1016/j.phymed.2022.154176 PMID: 35660354
pubmed: 35660354
pii: S0944-7113(22)00254-9
doi: 10.1016/j.phymed.2022.154176
pii:
doi:

Substances chimiques

IL1B protein, rat 0
Inflammasomes 0
Interleukin-1beta 0
NLR Family, Pyrin Domain-Containing 3 Protein 0
Nlrp3 protein, rat 0
Phenylpropionates 0
gamma-oryzanol SST9XCL51M

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

154176

Informations de copyright

Copyright © 2022. Published by Elsevier GmbH.

Auteurs

Hui Xu (H)

Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China.

Zi-Han Dai (ZH)

Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China.

Gao-Lu He (GL)

Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China.

Han-Chen Cai (HC)

Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China.

Xuan-Yang Chen (XY)

Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China.

Yan-Lin Chen (YL)

Department of Orthopaedics Surgery, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China. Electronic address: cylzxyy2871@163.com.

Cong Xu (C)

Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China. Electronic address: congxu@wmu.edu.cn.

Sun-Ren Sheng (SR)

Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China. Electronic address: shengsunren@wmu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Gamma-oryzanol alleviates intervertebral disc...
questionsmedicales.fr › Structures macromoléculaires › Complexes multiprotéiques › Inflammasomes › Gamma-oryzanol alleviates intervertebral disc...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Monokines › Interleukine-1 › Interleukine-1 bêta › Gamma-oryzanol alleviates intervertebral disc...
questionsmedicales.fr › Maladies ostéomusculaires › Maladies osseuses › Maladies du rachis › Dégénérescence de disque intervertébral › Gamma-oryzanol alleviates intervertebral disc...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Protéines NLR › Protéine-3 de la famille des NLR contenant un domaine pyrine › Gamma-oryzanol alleviates intervertebral disc...
questionsmedicales.fr › Tissus › Tissu conjonctif › Cartilage › Fibrocartilage › Disque intervertébral › Nucleus pulposus › Gamma-oryzanol alleviates intervertebral disc...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides carbocycliques › Phénylpropionates › Gamma-oryzanol alleviates intervertebral disc...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Gamma-oryzanol alleviates intervertebral disc...