Norisoboldine Reduces Arthritis Severity by Attenuating Inflammation, Oxidative Stress, and Extracellular Matrix Degradation in a Rat Model of Rheumatoid Arthritis.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent joint inflammation, pain, and tissue degradation. This study evaluates the therapeutic potential of Norisoboldine (NOR), an isoquinoline alkaloid from Lindera aggregata, in a rat model of RA. Methods: Rats were divided into five groups: normal control (G1), RA model (G2), NOR-treated groups at 15 mg/kg (G3) and 30 mg/kg (G4), and methotrexate-treated group (G5). NOR's anti-arthritic effects were assessed by measuring clinical arthritis scores and inflammatory markers (RF, CRP, TNF-α, IL-6, IL-10). Oxidative stress markers (MDA, SOD, catalase, GPx) and pathways (NF-κB/IKKβ and Nrf2/Keap1) were also evaluated. Histopathology assessed synovial inflammation and tissue degradation. Results: NOR treatment significantly reduced arthritis severity, as evidenced by decreased clinical arthritis scores and inflammatory markers in RA rats. NOR also exhibited strong antioxidant effects, demonstrated by decreased MDA levels and enhanced SOD, catalase, and GPx activities. NOR further downregulated matrix metalloproteinases (Mmp-2, Mmp-3), aggrecanases (Adamts-4, Adamts-5), and PCNA expression. Histopathology confirmed marked reductions in synovial inflammation and tissue damage in NOR-treated groups. Discussion: These findings suggest that NOR's anti-inflammatory and antioxidant properties contribute to reducing both inflammation and the overall severity of RA. NOR's multifaceted actions support its potential as a novel therapeutic agent for RA. Conclusion: NOR demonstrates protective effects in RA rats by reducing inflammation, oxidative stress, and extracellular matrix degradation, offering promise as a therapeutic option to manage RA pathology comprehensively.