Ulvan and Ulva oligosaccharides from Ulva sp. attenuate osteoarthritis in a high-fat diet and ligamentous meniscal injury-induced rat model

Abstract

Osteoarthritis (OA) is a chronic joint disease. It is marked by the progressive deterioration of subchondral bone, articular cartilage, and synovium, with obesity acting as a significant risk factor by promoting inflammation and cartilage degradation. Ulvan and Ulva oligosaccharides derived from Ulva sp. seaweed have shown anti-inflammatory properties that may be beneficial in this context. Therefore, the aim of this research was to determine the protective effect of ulvan and Ulva oligosaccharides from Ulva sp. on monosodium iodoacetate (MIA)-induced inflammation in SW1353 cells and in a high-fat-diet/ACL-meniscus-injury rat model of osteoarthritis. The Ulva extract (UE) was hydrolyzed with cellulase to obtain Ulva hydrolysate (UH). The rats were treated using UE (50 mg/kg) and three different doses of UH (UH1, 50 mg/kg; UH2, 100 mg/kg; UH5, 250 mg/kg). In addition, UH contains higher levels of total sugars (22.8 +/- 1.3%) and sulfated groups (18.4 +/- 0.2%) compared with UE (19.6% and 15.5%, respectively). Treatment with UE and UH significantly reduce matrix metalloproteinase-3 (MMP-3) and interleukin-6 levels and increase collagen type II alpha 1 level in MIA-induced SW1353 cells. The animal study revealed that UE and UH significantly decrease triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels. These treatments also reduced nitric oxide levels in OA rats and inhibited pro-inflammatory cytokines and mediators, MMP-3, and C-terminal cross-linked telopeptides of type II collagen (CTX-II). Additionally, UE and UH treatment reduced proteoglycan loss in cartilage lesions in OA rats after six weeks of treatment. These findings suggest that Ulvan and Ulva oligosaccharides from Ulva sp. may have potential as treatments for osteoarthritis.