Antiarthritic effect of chitosan nanoparticle loaded with embelin against adjuvant‐induced arthritis in Wistar rats

Abstract

Background Rheumatoid arthritis (RA) is associated with joint damage. Effectiveness of embelin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism, and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable embelin‐loaded chitosan nanoparticles (CS‐embelin NPs) for the treatment of RA. Methods The rats were made arthritic using a subcutaneous injection with 0.1 ml complete Freund's adjuvant (CFA) into the footpad of the left hind paw. CS‐embelin NPs (25 and 50 mg/kg) was administered from day 15 to day 28 after adjuvant injection. After the experimental period, the animals were sacrificed and various biochemical markers were assessed. Results Arthritic score and paw swelling were significantly reduced after treatment with CS‐embelin NPs. Arthritis‐induced rats showed a significant increase in malondialdehyde (MDA) and nitric oxide (NO) with a concomitant reduction of antioxidants in the paw tissue. CS‐embelin NPs (25 and 50 mg/kg) reduced MDA and NO levels and restored antioxidant levels to normalcy by mitigating oxidative stress. The arthritic rats exhibited elevated tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and interleukin‐1beta (IL‐1β) serum concentrations, upregulated TNF‐ α and IL–6 protein levels and upregulated nuclear factor‐kB (NF‐kB) mRNA expression in paw tissues. Treatment with CS‐embelin NPs (25 and 50 mg/kg) significantly reduced serum levels and down‐regulated inflammatory markers to normalcy, dose‐dependently. Conclusion The results suggest that CS‐embelin NPs displayed a protective effect against adjuvant‐induced arthritis in rats mediated through antioxidant and anti‐inflammatory effects.

Embelin: A novel XIAP inhibitor for the prevention and treatment of chronic diseases

“…[84] Additionally, embelin loaded chitosan nanoparticles (CS-embelin NPs) downregulated inflammatory cytokine levels of IL-1β, -6, , and TNF-α. [85,86] Moreover, embelin has also effectively upregulated myocardial expression of B-cell lymphoma-2 (Bcl-2) and repressed the expression of Bax, cytochrome c, cleaved-caspase-3 and -9, and PARP. [87] Besides regenerating islet cells in diabetic models, embelin therapy elevated the pancreatic antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST), and ascorbic acid (AA), and decreased the production and accumulation of reactive oxygen species (ROS).…”

“…Table 1 shows a detailed summary of the pharmacological activities of embelin against different chronic diseases. [50,74,[77][78][79][82][83][84][85][86][87][88][89]92,93,97, In this review, we discuss the diverse biological activities of embelin and explore its different cellular and molecular aspects in the prevention and treatment of traumatizing chronic diseases that are responsible for killing millions of lives worldwide.…”

Nano Drug Delivery Platforms for Dental Application: Infection Control and TMJ Management—A Review

“…Chitosan-based nanoparticles were prepared using the ionotropic gelation method where 1 g chitosan was fully dissolved in 50 milliliters glacial acetic acid 1%, mixed at 40 degrees to achieve a clear solution with nanoparticles having a size of 102.4 ± 3.2nm. Rats were induced with arthritis that showed a significant decrease in malondialdehyde (MDA) and nitric oxide (NO) levels which resulted in the return of normalcy of antioxidants [ 37 ]. Furthermore, inflammatory mediators such as TNFα, IL-1, IL-6, and IL-1B concentration in serum were reduced by administration of CS-NPs [ 37 ].…”

“…Rats were induced with arthritis that showed a significant decrease in malondialdehyde (MDA) and nitric oxide (NO) levels which resulted in the return of normalcy of antioxidants [ 37 ]. Furthermore, inflammatory mediators such as TNFα, IL-1, IL-6, and IL-1B concentration in serum were reduced by administration of CS-NPs [ 37 ].…”

Food-Derived Nanoscopic Drug Delivery Systems for Treatment of Rheumatoid Arthritis

“…CHS nanostructures loaded with anti-arthritic agents, e.g., NSAIDs [ 80 ], DMARDs [ 81 ], GCs [ 82 ], natural products [ 83 ], and zinc salts [ 84 ], have been reported with more potent efficacies than preparations without CHS ( Table 3 ). In order to improve stability and flexibility of CHS NPs, other materials have been incorporated in the preparations.…”