Modulation of Proinflammatory Cytokines by Parmotrema reticulatum Derived Dioxepine Derivative and Benzoic Methyl Ester in Adjuvant-Induced Arthritis.

Abstract

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 compound A & B to CFA (Freund's complete adjuvant) induced arthritis rat revealed reduction in arthritis complication 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 were observed there by inhibiting inflammation of synovial cavity and cartilage damage effectively. Hence from our results it is evident that Pr, Compound A & B has down regulated the inflammatory cytokines and can be a potential candidate to treat arthritis.