Bergenin Loaded Gum Xanthan Stabilized Silver Nanoparticles Suppress Synovial Inflammation Through Modulation of the Immune Response and Oxidative Stress in Adjuvant Induced Arthritic Rats

Bergenin (BG) is a naturally occurring C-glycoside with demonstrated anti-arthritic potential. Its therapeutic efficacy is compromised due to its lower absorption and instability at neutral-basic pH. The present study reports fabrication of gum xanthan (GX) stabilized silver nanoparticles (AgNPs) with BG for anti-arthritic activity in a CFA-induced arthritis model targeting ROS, cytokines and TLR expression. NPs were characterized through UV-vis, zetasizer, FT-IR and AFM. Oral administration of BG loaded NPs (1 mg kg) exhibited potent anti-arthritic activity with a minimal arthritic score, mild to moderate paw tissue swelling, reduced degenerative changes along with mild articular changes and less influx of inflammatory cells in macroscopic X-ray and histological examination. Administration of BG and its NPs suppressed the levels of reactive oxygen species (ROS) significantly as compared to the arthritic control group. Moreover, increased production of O˙ in human neutrophils, stimulated by opsonized zymosan (OZ) and phorbol-12-myristate-13-acetate (PMA) was also suppressed. BG and its loaded NPs were revealed to antagonize the oxidative stress via interference with the NADPH oxidase metabolic pathway. Their anti-oxidant activity was further assessed by their inhibitory effect against TLR (TRL-2 & -4) and cytokine (IL-1β, IL-6 and TNF-α) production. The current investigation validates GX stabilized AgNPs as stable and promising multi-targeted therapeutic nano-cargo for BG delivery with efficient treatment of RA.