Nitidine Chloride Alleviates Inflammation and Cellular Senescence in Murine Osteoarthritis Through Scavenging ROS

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.

Quantification and discovery of quality markers from Toddalia asiatica by UHPLC‐MS/MS coupled with chemometrics

“…(−)‐Lyoniresinol displayed inhibitory activity against the production of nitric oxide (NO) in LPS‐stimulated BV2 and RAW264.7 cells, with IC 50 values of 67.9 and 76.7 μM, respectively 28 . Nitidine chloride exerted anti‐inflammatory effects in mice with osteoarthritis by scavenging reactive oxygen species 29 . Norbraylin exhibited potent inhibitory activity against phosphodiesterase‐4, with an IC 50 value of 7.15 μM 30 .…”

“…28 Nitidine chloride exerted anti-inflammatory effects in mice with osteoarthritis by scavenging reactive oxygen species. 29 Norbraylin exhibited potent inhibitory activity against phosphodiesterase-4, with an IC 50 value of 7.15 μM. 30 Skimmianine displayed a synergistic effect with betulinic acid and apigenin in suppressing the CD36-mediated TLR2/NLRP3 inflammasome cascade.…”

“…These compounds exhibited diverse pharmacological activities, including anti-inflammatory, anticancer, and antiviral properties (Table S1). [27][28][29][30][31][32] Secondly, single-factor optimization and RSM were applied to optimize the extraction process of TA, including extraction solvent type, ethanol volume fraction, ultrasonic extraction time, and solid-liquid ratio. Thirdly, 21 batches of TA from various regions were extracted using the optimized extraction process, and the contents of multiple bioactive compounds in each batch was determined.…”