Frontiers in Pharmacology (Jul 2022)
Nitidine Chloride Alleviates Inflammation and Cellular Senescence in Murine Osteoarthritis Through Scavenging ROS
- Changjian Lin,
- Changjian Lin,
- Changjian Lin,
- Changjian Lin,
- Lujie Ge,
- Lujie Ge,
- Lujie Ge,
- Lujie Ge,
- Luping Tang,
- Yuzhe He,
- Yuzhe He,
- Yuzhe He,
- Yuzhe He,
- Safwat Adel Abdo Moqbel,
- Safwat Adel Abdo Moqbel,
- Safwat Adel Abdo Moqbel,
- Safwat Adel Abdo Moqbel,
- Kai Xu,
- Kai Xu,
- Kai Xu,
- Kai Xu,
- Diana Ma,
- Diana Ma,
- Diana Ma,
- Diana Ma,
- Xing Zhou,
- Xing Zhou,
- Xing Zhou,
- Xing Zhou,
- Jisheng Ran,
- Jisheng Ran,
- Jisheng Ran,
- Jisheng Ran,
- Lidong Wu,
- Lidong Wu,
- Lidong Wu,
- Lidong Wu
Affiliations
- Changjian Lin
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Changjian Lin
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Changjian Lin
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Changjian Lin
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- Lujie Ge
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Lujie Ge
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Lujie Ge
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Lujie Ge
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- Luping Tang
- Department of Emergency Medicine, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Yuzhe He
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Yuzhe He
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Yuzhe He
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Yuzhe He
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- Safwat Adel Abdo Moqbel
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Safwat Adel Abdo Moqbel
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Safwat Adel Abdo Moqbel
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Safwat Adel Abdo Moqbel
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- Kai Xu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Kai Xu
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Kai Xu
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Kai Xu
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- Diana Ma
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Diana Ma
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Diana Ma
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Diana Ma
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- Xing Zhou
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Xing Zhou
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Xing Zhou
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Xing Zhou
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- Jisheng Ran
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Jisheng Ran
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Jisheng Ran
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Jisheng Ran
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- Lidong Wu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Lidong Wu
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Lidong Wu
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Lidong Wu
- Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
- DOI
- https://doi.org/10.3389/fphar.2022.919940
- Journal volume & issue
-
Vol. 13
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.
Keywords
