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-1) 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 O2˙- 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.