Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting SIRT6 DOI Creative Commons
Xuezhong Wang, Xuyang Li, Jianlin Zhou

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 20, 2023

Abstract Background Osteoarthritis (OA), the most common type of arthritis, is a highly prevalent age-related joint disease particularly in subjects over 65 years old. The chronic rise senescent cells closely correlates with diseases including OA, and senescence-associated secretory phenotype (SASP) implicated pathogenesis OA cartilage degeneration. Sirtuin 6 (SIRT6) probable to be key senescence-related regulator. Fisetin (FST), natural flavonol flavonoid family, recommended senolytic that extends health lifespan. However, potential chondroprotective effects FST on rats remain largely unclarified. This study aimed investigate ameliorative relationship SIRT6, detailed mechanisms from both anti-inflammatory anti-senescent perspectives. Methods Rats were subjected destabilization medial meniscus (DMM) surgery induce experimental model vivo. Chondrocytes treated IL-1β utilized mimic cell vitro. Intra-articular injection FST, OSS_128167 (OSS, SIRT6 inhibitor), MDL800 (MDL, agonist) vivo or incubation IL-1β-induced rat chondrocytes vitro performed determine link SIRT6. Results level was negatively correlated severity. downregulation validated cartilages DMM IL-1β-treated chondrocytes. Of note, We demonstrated could activate Both administration activation using MDL rescued erosion, decreased extracellular matrix (ECM) degradation, prevented apoptosis, improved detrimental phenotype. alleviative against inflammation, ECM senescence also confirmed IL-1β-stimulated Conclusion loss occurs articular which linked aging. attenuates injury-induced aging-related changes by targeting

Language: Английский

Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways DOI Creative Commons

Gongbiao Lu,

Cunxin Zhang, Kang Li

et al.

Journal of Inflammation Research, Journal Year: 2023, Volume and Issue: Volume 16, P. 4777 - 4791

Published: Oct. 1, 2023

Purpose: To investigate the molecular mechanism underlying inhibitory effect of sinomenine (SN) on interleukin-1β (IL-1β)-induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate potential role SN preventing intervertebral disk degeneration (IDD). Methods: The Rat NPCs were cultured vitro identified using Hematoxylin-Eosin (HE) staining, toluidine blue immunofluorescence analysis. pretreated with or without SN, then induced IL-1β assess cell viability, ROS levels, apoptotic rates, wound healing ability. Relevant protein expression was detected Elisa, qPCR Western Blot techniques. either alone combination Nrf2-IN-1 SC, before being undergo by IL-1β. Apoptosis Hoechst while techniques assessed expression. caudal discs IDD, injection, co-injected levels IDD evaluated HE staining modified saffron-O-fix green cartilage staining. qPCR, Results: significantly reduced NPC activity, accumulation apoptosis, decreased rate, promoted secretion inflammatory factors, inhibited extracellular matrix synthesis. However, pretreatment effectively reversed these effects. Inhibition Keap1/Nrf2 signaling pathway activation NF-κB attenuated cytoprotective effects increased apoptosis. Acupuncture combined injection markedly disc rat spine, upregulated factors secretion, downregulated intervention notably enhanced antioxidant enzyme outcomes. Conclusion: can prevent IL-1β-induced ameliorate activating inhibiting pathway. Keywords: sinomenine, degeneration, cells, Nrf2,

Language: Английский

Citations

4
Phillygenin inhibits neuroinflammation and promotes functional recovery after spinal cord injury via TLR4 inhibition of the NF-κB signaling pathway DOI Creative Commons
Yu Zhang, Shining Xiao,

Fan Dan

et al.

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 48, P. 133 - 145

Published: Aug. 8, 2024

Spinal cord injuries (SCIs) trigger a cascade of detrimental processes, encompassing neuroinflammation and oxidative stress (OS), ultimately leading to neuronal damage. Phillygenin (PHI), isolated from forsythia, is used in number biomedical applications, known exhibit anti-neuroinflammation activity. In this study, we investigated the role mechanistic ability PHI activation microglia-mediated subsequent apoptosis following SCI.

Language: Английский

Citations

1
Compound 7 regulates microglia polarization and attenuates radiation-induced myelopathy via the Nrf2 signaling pathway in vivo and in vitro studies DOI Creative Commons
Han Wu, Jian Wu,

Jianzhuo Jiang

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Nov. 4, 2024

Abstract Background Radiation-induced myelopathy (RM) is a significant complication of radiotherapy with its mechanisms still not fully understood and lacking effective treatments. Compound 7 (C7) newly identified, potent, selective inhibitor the Keap1-Nrf2 interaction. This study aimed to explore protective effects C7 on RM in vitro vivo. Methods Western blotting, quantitative real‐time polymerase chain reaction (qRT‐PCR), reactive oxygen species (ROS) mitochondrial polarization, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, genetic editing techniques, locomotor functions, tissue staining were employed underlying radiation-induced primary rat microglia BV2 cells, as well models. Results In this study, we found that inhibited production pro-inflammation cytokines oxidative stress induced by irradiation vitro. Further, data revealed radiation worsened functions rats, significantly improved histological functional recovery rats. Mechanically, activated Nrf2 signaling promoted transformation from M1 M2 phenotype. Conclusion could ameliorate boosting promoting phenotype polarization

Language: Английский

Citations

1
[Effects of VX765 on osteoarthritis and chondrocyte inflammation in rats]. DOI

Wanran Huang,

Junxue Tu,

Ai-qing Qiao

et al.

PubMed, Journal Year: 2024, Volume and Issue: 38(1), P. 74 - 81

Published: Jan. 15, 2024

To investigate the effects and underlying mechanisms of VX765 on osteoarthritis (OA) chondrocytes inflammation in rats.

Language: Английский

Citations

0
The common link between sleep apnea syndrome and osteoarthritis: a literature review DOI Creative Commons

Lian Weng,

Yuxi Luo,

Xiongjunjie Luo

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 21, 2024

Patients with Osteoarthritis (OA) often also suffer from Sleep Apnea Syndrome (SAS), and many scholars have started to notice this link, although the relationship between two is still unclear. In review, we aim summarize current literature on these diseases, integrate evidence of OA OSA connection, explore discuss their potential common mechanisms, thus identify effective treatment methods for patients both SAS. Some shared characteristics conditions been identified, notably aging obesity as mutual risk factors. Both diseases are associated various biological processes or molecular pathways, including mitochondrial dysfunction, reactive oxygen species production, NF-kB pathway, HIF, IL-6, IL-8. SAS serves a factor OA, conversely, may influence progression The effects underreported in require more investigation. To effectively manage patients, timely intervention necessary while treating weight reduction being primary requirement, alongside combined treatments such Continuous positive airway pressure (CPAP) medications. Additionally, numerous studies drug development now aimed at inhibiting clearing certain ROS, NF-KB, Improving function might represent viable new strategy, further research into updates transplants essential.

Language: Английский

Citations

0
Phillygenin attenuates cell apoptosis and microglia activation in cerebral ischaemia–reperfusion rats through activation of peroxisome proliferator‐activated receptor γ DOI
Chao‐Jun Yan,

Guangwei Sun,

Changlong Hu

et al.

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2024, Volume and Issue: 51(11)

Published: Sept. 16, 2024

Ischaemic stroke is a common condition that can lead to cerebral ischaemia-reperfusion injury. Phillygenin (PHI), natural bioactive compound derived from Forsythia suspensa, has been shown play crucial role in regulating inflammation across various diseases. However, its specific regulatory effects ischaemic progression remain unclear. In this study, we established middle artery occlusion (MCAO) rat model. Treatment with PHI (50 or 100 mg/kg) significantly reduced infarction MCAO rats. treatment also mitigated the increased inflammatory response observed these Additionally, suppressed microglial activation by reducing iNOS expression, marker of M1-type polarization microglia, and attenuated brain tissue apoptosis Furthermore, PHI's anti-inflammatory rats were abrogated upon co-administration GW9662, peroxisome proliferator-activated receptor γ (PPARγ) inhibitor. summary, injury through PPARγ activation, suggesting potential as therapeutic agent for mitigating

Language: Английский

Citations

0
Pinus densiflora Root Extract Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Cartilage Degradation in Interleukin-1β and Monosodium Iodoacetate-Induced Osteoarthritis Models DOI Open Access
Young Joo Park, Dong Hae Shin, Hak Sung Lee

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(22), P. 3882 - 3882

Published: Nov. 14, 2024

Osteoarthritis (OA) is a common degenerative joint condition caused by an imbalance between cartilage synthesis and degradation, which disrupts homeostasis. This study investigated the anti-inflammatory joint-improving effects of

Language: Английский

Citations

0
SIRT2 regulates oxidative stress response in liver fibrosis mice through the NLRP3 inflammasome pathway DOI Creative Commons
Jingru Guo,

Junshu Nie,

Dongni Li

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 17, 2023

Abstract Liver fibrosis is a crucial step in the progression of various chronic liver diseases to cirrhosis, which can affect prognosis diseases. The NAD + dependent deacetylase sirtuins family member SIRT2 regulate inflammatory corpuscular pathway pathological processes, but its related mechanism not yet clear. This study established models wild-type and knockout mice, evaluated their effects on homeostasis using immunoblotting, immunofluorescence, histopathological staining methods. results indicate that deletion gene enhances NLRP3 acetylation, activates inflammasome pathway, accelerates oxidative stress. These findings suggest may be potential target for regulating restoring health.

Language: Английский

Citations

0
Recent advances in understanding molecular mechanisms and novel strategies for the treatment of osteoarthritis and other diseases related with cartilage defects DOI Creative Commons
Jiawei Li, Dongquan Shi, Di Chen

et al.

Journal of Orthopaedic Translation, Journal Year: 2023, Volume and Issue: 41, P. A1 - A2

Published: July 1, 2023

Language: Английский

Citations

0
Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting SIRT6 DOI Creative Commons
Xuezhong Wang, Xuyang Li, Jianlin Zhou

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 20, 2023

Abstract Background Osteoarthritis (OA), the most common type of arthritis, is a highly prevalent age-related joint disease particularly in subjects over 65 years old. The chronic rise senescent cells closely correlates with diseases including OA, and senescence-associated secretory phenotype (SASP) implicated pathogenesis OA cartilage degeneration. Sirtuin 6 (SIRT6) probable to be key senescence-related regulator. Fisetin (FST), natural flavonol flavonoid family, recommended senolytic that extends health lifespan. However, potential chondroprotective effects FST on rats remain largely unclarified. This study aimed investigate ameliorative relationship SIRT6, detailed mechanisms from both anti-inflammatory anti-senescent perspectives. Methods Rats were subjected destabilization medial meniscus (DMM) surgery induce experimental model vivo. Chondrocytes treated IL-1β utilized mimic cell vitro. Intra-articular injection FST, OSS_128167 (OSS, SIRT6 inhibitor), MDL800 (MDL, agonist) vivo or incubation IL-1β-induced rat chondrocytes vitro performed determine link SIRT6. Results level was negatively correlated severity. downregulation validated cartilages DMM IL-1β-treated chondrocytes. Of note, We demonstrated could activate Both administration activation using MDL rescued erosion, decreased extracellular matrix (ECM) degradation, prevented apoptosis, improved detrimental phenotype. alleviative against inflammation, ECM senescence also confirmed IL-1β-stimulated Conclusion loss occurs articular which linked aging. attenuates injury-induced aging-related changes by targeting

Language: Английский

Citations

0