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Nitidine Chloride Alleviates Inflammation and Cellular Senescence in Murine Osteoarthritis Through Scavenging ROS
Changjian Lin1,2,3,4, Lujie Ge1,2,3,4, Luping Tang5
1Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract:
Osteoarthritis (OA) is one of the most common chronic musculoskeletal disorder worldwide, representing a major source of disability, pain and socioeconomic burden. Yet the effective pharmaceutical treatments applied in the clinical works are merely symptomatic management with uncertainty around their long-term safety and efficacy, namely no drugs currently are capable of modulating the biological progression of OA. Here, we identified the potent anti-inflammatory as well as anti-oxidative properties of Nitidine Chloride (NitC), a bioactive phytochemical alkaloid extracted from natural herbs, in IL-1β-treated rat articular chondrocytes (RACs), LPS-stimulated RAW 264.7 and rat osteoarthritic models in vivo. We demonstrated NitC remarkably inhibited the production of inflammatory mediators including COX2 and iNOS, suppressed the activation of MAPK and NF-κB cell signaling pathway and reduced the expression of extracellular matrix (ECM) degrading enzymes including MMP3, MMP9 and MMP13 in IL-1β-treated RACs. Several emerging bioinformatics tools were performed to predict the underlying mechanism, the result of which indicated the potential reactive oxygen species (ROS) clearance potential of NitC. Further, NitC exhibited its anti-oxidative potential through ameliorating cellular senescence in IL-1β-treated RACs and decreasing NLRP3 inflammasomes activation in LPS-stimulated RAW 264.7 via scavenging ROS. Additionally, X-ray, micro-CT and other experiments in vivo demonstrated that intra-articular injection of NitC significantly alleviated the cartilage erosion, ECM degradation and subchondral alterations in OA progression. In conclusion, the present study reported the potent anti-inflammatory and anti-oxidative potential of NitC in OA biological process, providing a promising therapeutic agent for OA management.
Insights
Nitidine Chloride (NitC) shows potent anti-inflammatory and antioxidant properties, effectively reducing osteoarthritis progression by inhibiting inflammatory mediators and oxidative stress. This natural compound offers a promising therapeutic approach for managing osteoarthritis.
Area of Science:
- Pharmacology
- Biochemistry
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a prevalent chronic musculoskeletal disorder causing significant disability and socioeconomic burden.
- Current pharmaceutical treatments for OA offer only symptomatic relief with limited long-term safety and efficacy data.
- No existing drugs effectively modulate the biological progression of osteoarthritis.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-oxidative properties of Nitidine Chloride (NitC).
- To evaluate NitC's potential as a therapeutic agent for osteoarthritis management.
- To elucidate the underlying mechanisms of NitC's action in OA models.
Main Methods:
- In vitro studies using IL-1β-treated rat articular chondrocytes (RACs) and LPS-stimulated RAW 264.7 macrophages.
- In vivo studies using rat osteoarthritis models.
- Bioinformatics analysis to predict mechanisms of action.
- Assessment of inflammatory mediators, cell signaling pathways, extracellular matrix degradation, oxidative stress markers, and OA progression in vivo.
Main Results:
- NitC significantly inhibited inflammatory mediators (COX2, iNOS) and extracellular matrix degrading enzymes (MMP3, MMP9, MMP13) in RACs.
- NitC suppressed MAPK and NF-κB signaling pathways.
- NitC demonstrated anti-oxidative potential by scavenging reactive oxygen species (ROS), ameliorating cellular senescence, and reducing NLRP3 inflammasome activation.
- In vivo, intra-articular injection of NitC alleviated cartilage erosion, ECM degradation, and subchondral bone alterations in OA models.
Conclusions:
- Nitidine Chloride exhibits potent anti-inflammatory and anti-oxidative effects relevant to osteoarthritis.
- NitC effectively inhibits key molecular pathways and processes involved in OA pathogenesis.
- NitC presents a promising therapeutic candidate for modulating osteoarthritis progression.
