Protective effects of Catalpol to attenuate TNF- α and collagen-induced inflammation in vitro HFLS-RA cells and in vivo mice models for the treatment of rheumatoid arthritis.

Abstract

Background/rationale: Rheumatoid Arthritis (RA) is a prolonged autoimmune condition marked by persistent inflammation, causing joint damage and bone erosion. Catalpol (CAT), an iridoid glycoside, offers anti-inflammatory benefits, warranting its study in RA models.

Objective: To investigate the anti-inflammatory effects of CAT in RA by evaluating its impact on cellular and animal RA models.

Methods: In vitro biological actions of CAT were investigated by the methods of cell viability, proliferation, migration, invasion, apoptosis, ROS generation, double luciferase reporter assay for NF-κB-p65 activity, Nitrite release detection, and RT-qPCR for gene expression in Tumor Necrosis Factor-alpha (TNF-α)-induced Human Fibroblast-Like Synoviocytes from RA patients (HFLS-RA) (cellular RA model). Arthritis severity, joint cellular structure, gene expression, inflammatory factors, and joint inflammation studies were investigated in mice with collagen-induced arthritis (CIA) (animal RA model).

Key results: CAT treatment groups showed significant improvements (P < 0.001) in cell viability, migration, invasion, and apoptosis compared to the TNF-α-induced group. ROS generation and the activity of NF-κB-p65 were significantly reduced (P < 0.001). Nitrite release was decreased (P < 0.01, P < 0.001) in CAT-treatment groups. Pro-inflammatory and bone-metabolizing cytokine gene expression was markedly downregulated (P < 0.05, P < 0.001) in the cellular RA model. CIA mice treated with CAT exhibited significantly reduced arthritis severity, paw edema, and arthritis index (P < 0.05, P < 0.01). Joint pathology scores showed improvement (P < 0.001) in CAT-treatment groups. In the animal RA model, bone-metabolizing and inflammatory cytokine gene expression was significantly reduced in CAT-treatment groups (P < 0.01, P < 0.001).

Conclusion: CAT effectively reduces RA's inflammation and bone metabolism issues, suggesting its potential as a therapeutic agent for RA treatments. Key Points • Plant-derived Catalpol compound is an effective choice for rheumatoid arthritis treatment due to its anti-inflammatory potential. • CAT's effects were tested on TNF-α-induced HFLS-RA cells and in CIA mice, assessing cell viability, apoptosis, ROS generation, arthritis severity, inflammatory factors, and joint inflammation studies. • The administration of CAT could greatly enhance cell health and reduce inflammation markers and arthritis symptoms. • Observed significant reduction of RA inflammation and bone issues, confirming CAT as a therapeutic agent in RA treatment.