Modulation of Proinflammatory Cytokines by <i>Parmotrema reticulatum</i> Derived Dioxepine Derivative and Benzoic Methyl Ester in Adjuvant‐Induced Arthritis

The present investigation aims to study the therapeutic effect and to identify the lead molecules from lichen Parmotrema reticulatum (Pr) that can solve the complications associated with arthritis. Purification of Pr extract led to isolation of two lead molecules i.e. Compound A (a Dioxepine derivative) as 3-Hydroxy-9-hydroxymethyl-1,8-dimethyl-11-oxo-11H-dibenzo[b,e][1,4]dioxepine-4,7 dicarboxylic acid 7-methyl ester with molecular formula C₁₉H₁₆O₉; molecular weight 388.34. Compound B as 3-Hydroxy-5-methoxy-4-methyl-benzoic acid (a Benzoic methyl ester) with molecular formula C₉H₁₀O₄; molecular weight 182.2. In-silico investigation specific for inflammation revealed good binding affinity of both the compounds with the targeted proteins. Further continuous administration of Pr and novel compounds A and B to CFA (Freund's complete adjuvant) induced arthritis rat revealed a reduction in arthritis complications possibly by inhibiting the formation of edema. The variations in relative body weight along with paw swelling and arthritic scores were identified. Inhibition of expressions of RA markers like RF, CRP, TNF-𝛼, IL-1𝛽, IL-6, ALP, AST, ALT, and LDH was observed thereby inhibiting inflammation of the synovial cavity and cartilage damage effectively. Hence from our results, it is evident that Pr, Compound A and B has downregulated the inflammatory cytokines and can be a potential candidate to treat arthritis.