An iota-carrageenan isolated from marine alga Agardhiella ramosissima negatively modulates the inflammatory response in arthritis conditions

Abstract

The present study involves the structural characterization of an iota-carrageenan from Agardhiella ramosissima (IC-Ar) and its ability to suppress the inflammatory response in experimental arthritis. The IC-Ar was structurally characterized by Size Exclusion Chromatography (SEC) and Nuclear Magnetic Resonance (NMR) techniques. Experimentally, the mice were treated with IC-Ar (3, 10, or 30 mg/kg) e submitted to arthritis with zymosan and Complete Freund's Adjuvant (CFA). IC-Ar has a molecular mass of 730 KDa and contains 3,6 anhydro-α-d-galactose-2 sulfate (DA2S), β-d-galactose-4 sulfate (G4S) and glucose, structural characteristic typical of an iota carrageenan. IC-Ar treatment reduced zymosan-induced hypernociception, in a dose-dependent manner, accompanied by reduced edema, vascular permeability, and histopathological scores. Likewise, IC-Ar also significantly decreases MPO activity, leukocytes, neutrophils, IL-1β, and nitrite levels in the synovial fluid. Therapeutically, IC-Ar inhibited the hypernociception, edema, and arthritic index in both acute, sub-chronic, and chronic phases of CFA-induced arthritis. In summary, we demonstrated the protective efficacy of an iota-carrageenan extracted from A. ramosissima in arthritis models by negatively modulating the inflammatory response and by reducing polymorphonuclear cell migration, IL-1β, and nitrite levels, culminating in the inhibition of hypernociception and edema. Thus, IC-Ar could be a promising molecule to treat arthritis conditions.