Liqin Jin

Antitumor and immunomodulatory activity of polysaccharides from Sargassum fusiforme.

Sargassum fusiforme (Harv.) Setchel is an ingredient of Chinese herbal medicine that has been applied for thousands of years. This study was set up to evaluate the in vivo and in vitro anti-tumor potential of the polysaccharide (SFPS) from S. fusiforme and the immune response in tumor-bearing mice. SFPS was isolated by hot water extraction and ethanol precipitation. The mice inoculated with A549 cells were orally administrated with SFPS at the doses of 100 and 200mg/kg body weight for 28 days. The effects on the growth of tumor, serum TNF-α level, splenocyte proliferation, production of cytokines from peritoneal macrophages in A549-bearing mice were measured. Meanwhile, the cytotoxicity of SFPS on A549 cell line was also studied. Results showed that SFPS could not only significantly inhibit the growth of A549 lung adenocarcinoma in mice, but also remarkably promote IL-1 and TNF-α production from peritoneal macrophages, serum TNF-α level, and splenocytes proliferation in A549-bearing mice. The results indicate that SFPS has anti-tumor properties in vivo and in vitro, and improves the immune response in tumor-bearing mice. It could act as anti-tumor agent with immunomodulatory activity.

A polysaccharide from Sargassum fusiforme protects against immunosuppression in cyclophosphamide-treated mice.

A water-soluble polysaccharide (SFPS) isolated from Sargassum fusiforme was purified by DEAE-52 cellulose anion-exchange and Sephadex G-200 gel filtration chromatography. The high performance gel permeation chromatography (HPGPC) analysis showed that the average molecular weight (Mw) of SFPS was 299 kDa. The SFPS was composed of D-fucose, L-xylose, D-mannose and D-galactose in a molar ratio of 5.9:1.0:2.3:2.2. The results showed that SFPS stimulated proliferation and the cytokines (IL-2, IL-6 and IFN-γ) secretion of splenic lymphocytes in cyclophosphamide-induced immunosuppressed mice. SFPS markedly increased the phagocytic rates and cytokines (IL-2, IL-6 and TNF-α) secretion of peritoneal macrophages. Administration of SFPS significantly raised spleen index. It could act as an efficacious adjacent immunopotentiating therapy or an alternative means in lessening chemotherapy-induced immunosuppression, and also can be utilized as immunostimulants for food and pharmaceutical industries.

Protective effect of the polysaccharide from Ophiopogon japonicus on streptozotocin-induced diabetic rats.

The present study was designed to investigate the effect of OJP1, a polysaccharide isolated from the roots of Ophiopogon japonica, on blood lipid metabolism, antioxidant activity, as well as its protective effect on the liver and kidneys in diabetic rats. Results showed that OJP1 significantly reduced the MDA concentration and increased the activity of both GPx and SOD in the serum, liver and kidneys of diabetic rats. Moreover, the values of TG, TC, LDL-C and HDL-C in diabetic rats were significantly reversed by OJP1 treatment. Biochemical and histopathological analyses also showed that OJP1 can alleviate liver and kidneys injury in diabetic rats. The mRNA expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in diabetic rats decreased significantly after administration of OJP1. Altogether, these results suggest that OJP1 possess potent antioxidant activity and can protect the liver and kidneys from the injurious effects of diabetes.

Studies of macrophage immuno-modulating activity of polysaccharides isolated from Paecilomyces tenuipes.

The objective of this study was to evaluate the immunomodulatory effects of the Paecilomyces sinensis polysaccharides (PtP) on the activity of macrophages and human monocytes. A water-soluble polysaccharide, with estimated molecular weight of 2.04x10(4) Da, was isolated from P. sinensis. The results indicate that PtP can increase the activity of LDH and ACP in AMphi and PMphi of rats and human mononuclear cells, and enhance the pinocytic activity of macrophages and TNF-alpha production by human peripheral blood mononuclear cells (PBMC), suggesting that PtP had potent immunomodulatory properties and could be explored as a novel potential immunostimulants for the food and pharmaceutical purpose.

Sargassum fusiforme polysaccharide activates nuclear factor kappa-B (NF-κB) and induces cytokine production via Toll-like receptors.

This study was designed to investigate the mechanism of macrophage activation by the Sargassum fusiforme polysaccharide (SFPS). As a result, SFPS significantly enhanced cytokines and nitric oxide (NO) productions in peritoneal macrophages, and stimulated macrophages to produce the cytokines and NO through the induction of their genes expression. The pretreatment of peritoneal macrophages with special antibodies [Toll-like receptors (TLRs) antibody] significantly blocked SFPS-induced tumor necrosis factor alpha (TNF-α) and NO production. Furthermore, pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of NF-κB, effectively suppressed SFPS-induced TNF-α and interleukin 1β (IL-1β) secretion in peritoneal macrophages, indicating that SFPS stimulated macrophages to produce cytokines through the NF-κB pathway and the result was further confirmed by the experiment of Western blotting (WB) and confocal laser scanning microscope (CLSM). Taken together, these results suggest that SFPS-mediated induction of cytokines and NO production in macrophages is mediated, at least in part, by TLRs/NF-κB signaling pathway.

Protective effects of a novel trimerized sTNFRII on acute liver injury

TNF α plays a central role in the pathogenesis of inflammatory diseases such as rheumatoid arthritis and murine acute liver injury induced by injection of D-galactosamine and subsequent LPS. Recombinant Fc-fused soluble TNF receptor II (sTNFRII-Fc) has been used in the treatment of rheumatoid arthritis for a decade. We have recently constructed a novel fusion protein sTNFRII-gAD, which is composed of a soluble TNF receptor II and a globular domain of adiponectin. Utilizing the inclination of gAD to form homologous trimer naturally, we sought to explore TNFα antagonism of the novel trimerized sTNFRII-gAD and meantime compare TNFα-neutralizing effects in vitro and in vivo between sTNFRII-Fc and sTNFRII-gAD. Here, we evaluated the TNFα-antagonizing activity of sTNFRII-gAD with TNFα-induced L929 cytotoxicity assay. Furthermore, sTNFRII-Fc or sTNFRII-gAD was administered simultaneously with d-galactosamine 1h prior to LPS injection in the murine model of acute liver injury. Serum TNFα and TNFα-sTNFRII-gAD complex were measured by ELISA and the liver injury was assessed through alanine transaminase measurement and liver histological analysis. sTNFRII-gAD was shown to have higher TNFα-neutralizing activity than sTNFRII-Fc (p<0.05) in the L929 cytotoxicity assay. With a significant attenuation of murine lethality (p<0.05), sTNFRII-gAD showed more protective effects than sTNFRII-Fc in the murine model of acute liver injury. These results demonstrated that sTNFRII-gAD was more efficacious than sTNFRII-Fc as a TNFα antagonist, highlighting the potential of sTNFRII-gAD for the treatment of diseases associated with excessive TNFα.

Cardiovascular protective effect of polysaccharide from Ophiopogon japonicus in diabetic rats

Ophiopogon japonicus (Thunb.) Ker-Gawl is a well known traditional Chinese medicine used to treat cardiovascular and chronic inflammatory diseases for thousands of years. The present study was set up to investigate the protective effects of O. japonicus polysaccharide (OJP1) on cardiovascular injuries in diabetic rats. Results showed that OJP1 significantly reduced the MDA concentration and increased the activities of GPx, CAT and SOD in heart of diabetic rats. The levels of AGE, hs-CRP, sICAM-1, NO and ET-1 in diabetic rats were significantly reversed by OJP1 treatment. In addition, the level of ET-1 mRNA was decreased significantly, whereas eNOS mRNA level was increased after administration of OJP1. Meanwhile, the histopathological analysis showed that OJP1 alleviates the heart injury in diabetic rats. Together, these results suggest that OJP1 maintains the antioxidant enzyme levels and improves cardiovascular performance in diabetic rats.