Alginate oligosaccharides

Alginate oligosaccharide (AOS) is a kind of functional oligosaccharides obtained from the degradation of alginate, which has functional properties such as anti-inflammatory, antibacterial, and antioxidant activity. The aim of this study was to investigate whether AOS could alleviate Salmonella enterica serovar Typhimurium (S. Typhimurium)-induced liver injury. In our study, we found that AOS could alleviate S. Typhimurium-caused weight loss, enlargement of the liver and spleen in mice. In addition, AOS attenuated S. Typhimurium-induced inflammatory response as evidenced by the reduced ratio of AST/ALT, and lower the mRNA levels of Il-6, Il-1β, Tnf-α, Ccl3, and Ccl8. Moreover, AOS reduced H₂O₂ activity and Ho-1 gene expression. TUNEL staining and Western blot results showed that AOS reduced S. Typhimurium-induced hepatic apoptosis. Further study showed that AOS suppressed S. Typhimurium-induced increase in gene expression levels of Tlr2, Tlr4, and Myd88 as well as protein expression levels of TLR2 and p-NF-κB p65. The 16S rRNA results of colonic contents showed that AOS increased the relative abundance of Lactobacillus and decreased Alistipes, Helicobacter, and Bacteroides. Analyses at the species level showed that the AOS + ST group increased the abundance of Lactobacillus johnsonii (L. johnsonii) and Limosilactobacillus reuteri (formely Lactobacillus reuteri, L. reuteri). In addition, Lactobacillus johnsonii culture supernatant and Limosilactobacillus reuteri culture supernatant partially reduced gene expression levels of pro-inflammatory cytokines and chemokines induced by lipopolysaccharide. In conclusion, the alleviation of S. Typhimurium-induced liver injury by AOS may be related to the reduction of inflammatory response, oxidative stress, apoptosis, and regulation of the gut microbiota.

Excess extracellular matrix (ECM) deposition is the characteristic of renal fibrosis, owing to the imbalance between synthesis and degradation. Fibronectin could regulate the deposition of other ECM, thus plays a crucial role in the progression of renal fibrosis. Mannose receptor C type 1 (MRC1), largely expressed on macrophages, owns an extracellular fibronectin type II domain that binds to and internalizes collagen and thus involves in fibrosis modulation. The purpose of the present study was to investigate whether MRC1 participates in the internalization of fibronectin and whether alginate oligosaccharides (AOSC), a degradation product of alginate, has beneficial effects in the resolution of renal fibrosis via MRC1.

Renal fibrosis models were constructed by unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (UIRI) in MRC1-WT and MRC1-KO mice. RAW264.7 cells were treated with TGF-β1 to induce pro-fibrotic responses. Expression of fibrotic markers and fibronectin endocytosis were examined.

MRC1 gene knockout aggravated renal fibrosis in UUO and UIRI models. Inhibition of MRC1 exacerbated TGF-β1-induced pro-fibrotic responses in RAW264.7 cells. MRC1 regulated integrin β1-mediated fibronectin endocytosis through Arp2/3-Kindlin-2 signaling pathway. AOSC improved renal fibrosis by increasing MRC1 expression and endocytosis of fibronectin.

Our findings highlight the importance of MRC1 and fibronectin endocytosis in the development of renal fibrosis, suggesting that activation of MRC1 by AOSC is probably a therapeutic option to delay the progress of kidney fibrosis.