Anti-arthritic Activity of Citral Against Complete Freund’s Adjuvant-induced Arthritis in Rats Through NF-κB Signaling Pathway

Background: Citral is a bioactive compound found in lemongrass oil. It functions as an antioxidant and possesses anti-inflammatory qualities. Objectives: The purpose of this study was to assess the anti-arthritic benefits of citral using a rat model with an adjuvant arthritis paradigm. Experimental Procedures: In Swiss Albino Wistar rats, arthritis was produced by intradermal injection of Freund’s adjuvant (0.1 mL) into their hind paw. Arthritic animals were given citral orally for a duration of 8 days, beginning on the 11th day and lasting until the 18th day after the adjuvant injection. Effect of citral was assessed by measuring liver indicators [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)], lipid peroxidation markers [thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide (LOOH)], antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH)], spleen enzyme activity, blood cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB)], and NF-κB/transforming growth factor-beta (TGF-β) messenger ribonucleic acid (mRNA) expression in control and experimental animals. Results: Animals with arthritis produced by adjuvant injection exhibited a large rise in hepatic markers, lipid peroxidative markers, lysosomal enzymes, and inflammatory cytokines, while antioxidant enzymes showed a significant drop compared to control rats. Administering citral orally resulted in a dramatic modification of the identified biochemical abnormalities in arthritic animals, bringing them closer to normal circumstances and restoring them to normalcy. Moreover, there was an elevation in the levels of inflammatory and fibrotic markers such as NF-κB/TGF-β in rats with induced arthritis. Rats with arthritis showed a significant reduction in NF-κB and TGF-β expression after receiving citral. Conclusion: This study indicates that citral demonstrates significant anti-arthritic, inflammation-suppressing, and anti-fibrotic properties in experimental arthritis models.