Abstract
Inflammation plays a critical role in the pathogenesis of osteoarthritis (OA). The objective of this study was to investigate the anti-inflammatory and chondroprotective properties of Artemisia annua L. water extract (AWE) following the induction of inflammation in cartilage cells (SW1353 cell) through the administration of interleukin-1 beta (IL-1β). We demonstrated significant antioxidant activity, as evidenced by elevated total phenolic and flavonoid content, in addition to robust free radical scavenging capacity, as assessed through DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. Its cytotoxic effects were assessed at a concentration of 200 μg/mL, where no cytotoxic signs were observed in SW1353 cells treated with IL-1β; the levels of reactive oxygen species (ROS) were notably reduced in a dose-dependent manner. The principal inflammatory markers, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), were significantly diminished by AWE treatment. AWE administration led to a dose-dependent reduction in the expression of key proteins involved in the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways, ultimately resulting in a decrease in the release of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-13, which are known to contribute to cartilage degradation. Additionally, the levels of degraded collagen type II in the cartilage cells were restored. These findings suggest that reducing oxidative stress and inflammation, along with inhibiting activated MAPK and NF-κB signaling pathways, may ameliorate the progression of IL-1β-induced OA. Furthermore, a molecular docking analysis revealed a strong binding affinity of MMP-13, a critical mediator in the pathogenesis of OA. Six compounds were identified in AWE, corroborating its potential antioxidant and anti-inflammatory effects. Therefore, AWE may serve as a potentially useful therapeutic agent against OA by modulating inflammation-related mechanisms.