SummaryWhile there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of proteins. We describe a novel pellet formulation consisting of cross-linked dextran coated with an acrylic co-polymer that protects the complement inhibitor CR2-Crry from destruction in the gastrointestinal tract. CR2-Crry containing pellets administered by gavage, were characterized using a therapeutic protocol in a mouse model of dextran sulphate sodium (DSS)-induced colitis. Oral treatment of established colitis over a 5-day period significantly reduced mucosal inflammation and injury, with similar therapeutic benefit whether or not the proton pump inhibitor, omeprazole, was co-administered. Reduction in injury was associated with the targeting of CR2-Crry to the mucosal surface and reduced local complement activation. Treatment had no effect on systemic complement activity. This novel method for oral delivery of a targeted protein complement inhibitor will reduce systemic effects, thereby decreasing the risk of opportunistic infection, as well as lowering the required dose and treatment cost and improving patient compliance. Furthermore, the novel delivery system described here may provide similar benefits for administration of other protein-based drugs, such as anti-tumour necrosis factor-α antibodies.
No abstract
In aging, increases in oxidative stress and inflammation cause an imbalance in the metabolic activity of chondrocytes leading to onset and progression of osteoarthritis. Resveratrol, a polyphenol rich in grapes has shown to inhibit chondrocyte apoptosis and suppress cyclooxygenase (COX‐2). Our study investigated the effect of whole grape polyphenols on cartilage cell integrity and markers of cartilage health using SW 1353 human chondrosarcoma cells that are compatible to primary chondrocytes. Whole grape polyphenols (WGP) were extracted from grape powder and concentrations were determined using Folin‐Calteau assay. For all experiments, cells treated with WGP were stimulated with the inflammatory compound, tert‐butyl hydroperoxide (tbHP). Cell proliferation significantly (p<.05) increased in a dose dependent manner with WGP at 20ug/ml (147% vs. Control). Cartilage degradation as indicated by glycoprotein‐39 (YKL‐40) levels was significantly lower with the three highest doses of WGP in comparison to control and tbHP stimulated cells. Toluidine blue and Safarin O staining indicated increase presence of type II collagen and proteoglycan in WGP treated cells. Using In‐Cell colorimetric ELISA, we did not observe a significant effect on COX‐2 protein expression with any WGP doses. Elucidation of mechanisms by which WGP protect cartilage cell destruction in presence of an inflammatory agent are warranted. Grant Funding Source: Supported by California Table Grape Commission
Rheumatoid arthritis (RA) is an autoimmune and a chronic inflammatory disease resulting in joint destruction and disability in the adult population. The etiology of this condition is not well understood and presently there is no cure for this disease. The accumulation and proliferation of fibroblast‐like synoviocytes may be involved in cartilage destruction. Proinflammatory cytokines such as interleukin 1‐beta (IL‐1β) and tumor‐necrosis factor‐alpha (TNFα) are implicated in the progression of RA. Both in vitro and in vivo studies support an anti‐inflammatory role of dietary polyphenols, the bioactive constituents found in fruits and vegetables. Hence we investigated the anti‐proliferative and anti‐inflammatory role of blueberry polyphenols (BBP) using rabbit synoviocytes stimulated with TNFα. BBP significantly decreased cell proliferation (p < 0.05) in a dose dependent manner reaching 34.1% vs Control at a dosage of 200mg/ml. In‐Cell ELISA analysis for cyclooxygenase (COX‐1) and COX‐2 showed a significant decline with increasing doses of BBP. Post TNFα stimulation, cells treated with BBP resulted in decreases in IL‐1β and Nuclear Factor Kappa B (NF‐κB) protein expressions. Our results suggest that down‐regulation of proinflammatory cytokines and transcription factor NF‐κB by naturally‐occurring bioactives such as blueberry polyphenols may be an appropriate therapeutic strategy for rheumatoid arthritis.Support or Funding InformationPartially supported from Human Nutrition Research Funds at Texas Woman's University. Lyophilized blueberry powder was generously provided by the US Highbush Blueberry Council.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.