Anti-arthritic potential of Cassia fistula leaf extracts and sennoside B via NF-κB inhibition: In vivo and in vitro pre-clinical study.

objectiveRheumatoid arthritis (RA) is a chronic autoimmune disorder with complex pathophysiology. Disease cycle involves immune/inflammatory cells (macrophages, CD4 + , T, and B-cells) that directly/indirectly augment NF- κB mediated inflammation/oxidative stress and vice-versa creating a vicious loop that worsens disease. Inhibition of NF-κB signalling has emerged as a target for RA alleviation thus, this study evaluates the capability of Cassia fistula leaf extracts in supressing NF-κB signalling and contribution of sennoside B in extract efficacy.

methodsExtracts were prepared and its anti-inflammatory (IL-1β, TNF-α, IL-6, IL-17a), anti-oxidant (NO, MDA, catalase, reduced glutathione), NF-κB inhibition potential, and its effect on joint microstructure was evaluated on collagen-induced arthritis. Extracts were characterized using LC-MS and effect of sennoside B (anthraquinone glycoside detected in extracts) on NF-κB signalling was evaluated on LPS stimulated peritoneal macrophages.

resultsEthanolic extract of C. fistula leaf significantly inhibited NF-κB signalling (transcriptional/translational level), which led to significant reduction of inflammatory mediators (IL-1β, TNF-α, IL-6, IL-17a), and restored redox imbalance (NO, MDA, catalase, and reduced glutathione). Reduced NF-κB activity supressed tissue remodelling and osteoclastogenesis markers (MMP-2, MMP-9, MMP-13, and RANKL) which resulted in joint microstructure safe-guarding, also reflected as reduced paw swelling, paw volume and disease score significantly. Sennoside B showed strong anti-inflammatory and NF-κB inhibition against LPS-stimulated peritoneal macrophages.

conclusionEthanolic extract of C. fistula leaves alleviate RA by modulating NF-κB mediated inflammation and oxidative stress and disrupts the disease worsening feedback cycle. Sennoside B's capability to suppress NF-κB production/activation also plays an important role in increasing extract efficacy.