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Nitidine Chloride Alleviates Inflammation and Cellular Senescence in Murine Osteoarthritis Through Scavenging ROS
Frontiers in Pharmacology ( IF 4.4 ) Pub Date : 2022-07-22 , DOI: 10.3389/fphar.2022.919940
Changjian Lin 1, 2, 3, 4 , Lujie Ge 1, 2, 3, 4 , Luping Tang 5 , Yuzhe He 1, 2, 3, 4 , Safwat Adel Abdo Moqbel 1, 2, 3, 4 , Kai Xu 1, 2, 3, 4 , Diana Ma 1, 2, 3, 4 , Xing Zhou 1, 2, 3, 4 , Jisheng Ran 1, 2, 3, 4 , Lidong Wu 1, 2, 3, 4
Affiliation  

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.



中文翻译:

Nitidine Chloride 通过清除 ROS 缓解小鼠骨关节炎的炎症和细胞衰老

骨关节炎 (OA) 是全世界最常见的慢性肌肉骨骼疾病之一,是残疾、疼痛和社会经济负担的主要来源。然而,临床工作中应用的有效药物治疗仅仅是对症治疗,其长期安全性和有效性尚不确定,即目前尚无药物能够调节OA的生物学进展。在这里,我们在 IL-1β 处理的大鼠关节软骨细胞 (RACs)、LPS 刺激的 RAW 264.7 中鉴定了 Nitidine Chloride (NitC)(一种从天然草药中提取的生物活性植物化学生物碱)的强效抗炎和抗氧化特性和大鼠骨关节炎模型体内. 我们证明 NitC 显着抑制了包括 COX2 和 iNOS 在内的炎症介质的产生,抑制了 MAPK 和 NF-κB 细胞信号通路的激活,并降低了 IL-1β- 中包括 MMP3、MMP9 和 MMP13 在内的细胞外基质 (ECM) 降解酶的表达。处理过的 RAC。使用了几种新兴的生物信息学工具来预测潜在机制,其结果表明了 NitC 的潜在活性氧 (ROS) 清除潜力。此外,NitC 通过改善 IL-1β 处理的 RAC 中的细胞衰老和降低 LPS 刺激的 RAW 264.7 中的 NLRP3 炎性体活化而表现出其抗氧化潜力通过清除 ROS。此外,X 射线、显微 CT 和其他实验体内表明关节内注射 NitC 显着减轻了 OA 进展中的软骨侵蚀、ECM 降解和软骨下改变。总之,本研究报告了 NitC 在 OA 生物过程中的强效抗炎和抗氧化潜力,为 OA 管理提供了一种有前途的治疗剂。

更新日期:2022-07-22
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