Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund’s adjuvant (CFA)-induced arthritis in a pre-clinical model in rats. Rheumatoid arthritis was induced by injecting CFA intra-dermally in the sub-plantar region of the left hind paw of rats. Chrysin (50 and 100 mg/kg) and piroxicam (10 mg/kg) were given to rats with established arthritis. The model of arthritis was characterized using an index of arthritis, with hematological, biological, molecular, and histopathological parameters. Treatment with chrysin significantly reduced the arthritis score, inflammatory cells, erythrocyte sedimentation rate, and rheumatoid factor. Chrysin also reduced the mRNA levels of tumor necrosis factor, nuclear factor kappa-B, and toll-like recepter-2 and increased anti-inflammatory cytokines interleukin-4 and -10, as well as the hemoglobin levels. Using histopathology and microscopy, chrysin reduced the severity of arthritis in joints, infiltration of inflammatory cells, subcutaneous inflammation, cartilage erosion, bone erosion, and pannus formation. Chrysin showed comparable effects to piroxicam, which is used for the treatment of rheumatoid arthritis. The results showed that chrysin possesses anti-inflammatory and immunomodulatory effects that make it a potential drug for the treatment of arthritis.

Background and Objectives: This study was planned to investigate the anti-arthritic property of flowers of E. crassipes in a Sprague–Dawley rat model by administering Freund’s Complete Adjuvant (FCA). Materials and Methods: Arthritis was induced at day 0 in all rats except negative controls, while arthritic progress and paw edema were analyzed on specific days (8th, 13th, 18th, and 23rd) via the macroscopic arthritic scale and a digital Vernier caliper, respectively. Histopathological parameters were examined using a Hematoxylin and Eosin (H&E) staining method. Blood samples were withdrawn from rats to investigate the effects of the E. crassipes flower on the mRNA expression values of inflammatory markers, via a reverse transcription PCR technique. Serum samples were used to determine prostaglandin E2 (PGE2) levels using enzyme-linked immunosorbent assay (ELISA). Values of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine, and urea, besides hematological parameters, i.e., the hemoglobin (Hb) content and complete blood count (CBC), were investigated. Results: The data showed that E. crassipes inhibited the arthritic progress and ameliorated the paw edema. The amelioration of parameters assessed via the histopathological analysis of ankle joints, as well as via hematological analysis, confirmed the diminution of rheumatoid arthritis (RA) in the plant-treated groups. Treatment with E. crassipes inhibited the expression levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6), nuclear factor KappaB (NF-κB), matrix metalloproteinase (MMP-2 and MMP-3), and vascular endothelial growth factor (VEGF). Serum PGE2 levels were also found to be reduced in treatment groups. A biochemical investigation revealed the improvements in hepatic markers in plant-treated groups. The data indicated that the plant has no hepatotoxic or nephrotoxic effects at the studied dose. GC-MS (Gas Chromatography-Mass Spectrometry) analysis displayed the presence of phytochemicals having known anti-inflammatory and antioxidant properties. Conclusions: Therefore, it may be concluded that E. crassipes possesses anti-arthritic characteristics that could be attributed to the modulation of pro-inflammatory cytokines, MMPs, and PGE2 levels.