Effect of chitosan oligosaccharide-conjugated selenium on improving immune function and blocking gastric cancer growth.

Selenium (Se) is a potential chemopreventive or chemotherapeutic agent against malignant tumor. Selenium-oligosaccharides are important selenium source of dietary supplementation. Due to the insufficient natural production, it is therefore urgent to develop selenium-oligosaccharides by artificial synthesis. Chitosan, the N-deacetylated derivative of chitin, has been applied widely in biomedical field, owing to its nontoxicity, hydrophilicity, biocompatibility, and biodegradation. While chitosan is water insoluble at neutral pH, limiting its application in physiological conditions. Chitosan oligosaccharide (COS), the hydrolysate of chitosan, is readily soluble in water because of the shorter chain lengths of the oligomers and the free amino groups in the D-glucosamine units. This study was aimed at preparing COS-conjugated selenium (COS-Se) and examining the toxicity and ability on improving immune function and blocking gastric cancer growth. Our results demonstrated that COS-Se displayed directly co-mitogenic and mitogenic actions on mouse splenocytes proliferation in vitro. Besides, COS-Se treatment could effectively elevate phagocytosis and increase the secretion of anti-inflammatory cytokine in mouse peritoneal macrophages. Further in vivo experiments showed that COS-Se exhibited immuno-enhancing effects through promoting the phagocytic index, spleen index and thymus index with no obvious toxicity to Kunming mice. Moreover, COS-Se inhibited proliferation and metastasis of human gastric cancer cells, with non-toxic effects on the normal fibroblast cells in vitro. COS-Se supplementation could significantly repress the growth of gastric adenocarcinoma through reducing levels of CD34, vascular endothelial growth factor and matrix metalloproteinase-9 of nude mice. In conclusion, COS-Se was non-toxic and showed great potential as a functional food ingredient in cancer prevention.

Potential Analysis and Preparation of Chitosan Oligosaccharides as Oral Nutritional Supplements of Cancer Adjuvant Therapy.

Cancer is considered to have an adverse influence on health around the world. Chitosan, a linear polysaccharide that contains copolymers of ß -1-4 linked d-glucosamine and N-acetyl-d-glucosamine units, has been widely used in the field of biomedicine, owing to its nontoxicity, biocompatibility, biodegradability, and hemocompatibility. This study was aimed at preparing the chitosan oligosaccharides (COS) and examining its ability on suppressing lung cancer in vitro and in vivo. Human non-small-cell lung cancer A549 cells model and C57BL/6 mice bearing lung cancer model were adopted. COS showed inhibition on the viability and proliferation of lung carcinoma cells (A549) in time-dependent manners, but no cytotoxicity to human liver cell (HL-7702). Moreover, COS could significantly increase Bax expression of A549 cells while decreasing Bcl-2 expression. COS supplementation significantly inhibited the growth of Lewis tissues and promoted necrosis of tumor cells in vivo. After treatment with COS, significantly elevated concentrations of Bax and reduced expression of Bcl-2 in tumor tissues, as well as elevated levels of TNF- α , IL-2, Fas and Fas-L in mice serum were observed (p < 0.05). In conclusion, COS had certain anti-tumor effects and potential application as a synergic functional food ingredient to prevent cancer.

Dietary Natural N-Acetyl-d-Glucosamine Prevents Bone Loss in Ovariectomized Rat Model of Postmenopausal Osteoporosis.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.

Preparation and pharmacological evaluation of norcantharidin-conjugated carboxymethyl chitosan in mice bearing hepatocellular carcinoma.

In this study, norcantharidin (NCTD), a small-molecule anticancer drug derived from Chinese traditional medicine blister beetle (Mylabris), was conjugated covalently onto carboxymethyl chitosan (CMCS). Then the hepatocellular carcinoma therapeutic properties and liver-protective effects were investigated through orthotopic transplantation tumor model. Results showed that the obtained CMCS-NCTD demonstrated remarkable anti-growth efficacy against hepatocellular 22 in mice. Significant improvement of the liver injury caused by cancer cells was observed in tumor-bearing mice administrated with CMCS-NCTD. Moreover, CMCS-NCTD remarkably increased the serum levels of TNF-α, IFN-γ, TIMP-1 and E-cadherin in mice treated for 12days. Administration of CMCS-NCTD significantly reduced the elevated serum ALT, AST, VEGF and MMP-9 levels of tumor-bearing mice. In addition, activities of SOD and GSH-Px in serum or homogenate of the CMCS-NCTD treated mice were significantly high when compared with model control group. Our data suggested that CMCS-NCTD was a promising candidate as an anti-hepatoma and liver-protection compound.