Ke-Xue Zhu

Ganoderma atrum polysaccharide induces anti‐tumor activity via the mitochondrial apoptotic pathway related to activation of host immune response

Ganoderma atrum polysaccharide (PSG‐1), the major active ingredient isolated from Ganoderma atrum, has been suggested as a candidate for cancer therapy. The aim of this study was to investigate the anti‐tumor effect of PSG‐1 using sarcoma 180 (S‐180) transplanted mice and further to examine the molecular mechanisms of PSG‐1‐induced anti‐tumor effect. Results showed that PSG‐1 significantly inhibited tumor growth in S‐180‐bearing mice. PSG‐1‐induced tumor apoptosis was associated with the alteration of Bcl‐2 family proteins, increase of reactive oxygen species generation, loss of mitochondrial membrane potential (Δψm), release of cytochrome c from the mitochondria into cytosol, and activation of caspase‐3 and ‐9. Elevation of immune function was also shown during PSG‐1‐induced tumor apoptosis, as evidenced by increase of spleen and thymus indexes, lymphocyte proliferation, concentrations of tumor necrosis factor (TNF)‐α, and interleukin‐2 in serum. Furthermore, the combined treatment of PSG‐1 and cyclophosphamide (CTX) results in an enhancement of the anti‐tumor effect of CTX alone via increased host immune response. These results suggested that PSG‐1 had a potent anti‐tumor activity by induction of tumor apoptosis through mitochondrial pathways, and immunoenhancement effect of PSG‐1 was related to its anti‐tumor effect. In addition, PSG‐1 enhanced CTX‐induced anti‐tumor activity in S‐180‐bearing mice. J. Cell. Biochem. 112: 860–871, 2011.

A newly identified polysaccharide from Ganoderma atrum attenuates hyperglycemia and hyperlipidemia

A polysaccharide from Ganoderma atrum (PSG-1) was purified and characterized, and its hypoglycemic and hypolipidemic effects were investigated in high fat diet- and streptozotocin-induced type 2 diabetic rats. Oral administration of PSG-1 at 200 or 400 mg/kg body weight significantly reduced fasting blood glucose and serum insulin levels. PSG-1 significantly decreased the levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, free fatty acid and insulin resistance, and increased high-density lipoprotein cholesterol level and insulin sensitivity. In addition, PSG-1 inhibited the expression of pro-apoptotic protein, Bax and increased the expression of anti-apoptotic protein, Bcl-2 in pancreatic cells, suggesting that PSG-1 exerted a protective role in the pancreas of diabetic rats. These results indicated that PSG-1 may have a potential for the treatment of hyperglycemia, hyperlipidemia, hyperinsulinemia and insulin resistance in type 2 diabetes.

Ganoderma atrum polysaccharide improves aortic relaxation in diabetic rats via PI3K/Akt pathway

A newly identified polysaccharide (PSG-1) has been purified from Ganoderma atrum. The study was to investigate the protective effect of PSG-1 on diabetes-induced endothelial dysfunction in rat aorta. Rats were fed a high fat diet for 8 weeks and then injected with a low dose of streptozotocin to induce type 2 diabetes. The diabetic rats were orally treated with PSG-1 for 4 weeks. It was found that administration of PSG-1 significantly reduced levels of fasting blood glucose, improved endothelium-dependent aortic relaxation, increased levels of phosphoinositide 3-kinase (PI3K), phospho-Akt (p-Akt), endothelial nitric oxide synthase (eNOS) and nitric oxide in the aorta from diabetic rats, compared to un-treated diabetics. These results suggested that the protective effects of PSG-1 against endothelial dysfunction may be related to activation of the PI3K/Akt/eNOS pathway.

A Polysaccharide from Ganoderma atrum Improves Liver Function in Type 2 Diabetic Rats via Antioxidant Action and Short-Chain Fatty Acids Excretion

The present study was to evaluate the beneficial effect of polysaccharide isolated from Ganoderma atrum (PSG-1) on liver function in type 2 diabetic rats. Results showed that PSG-1 decreased the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), while increasing hepatic glycogen levels. PSG-1 also exerted strong antioxidant activities, together with upregulated mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), glucose transporter-4 (GLUT4), phosphoinositide 3-kinase (PI3K), and phosphorylated-Akt (p-Akt) in the liver of diabetic rats. Moreover, the concentrations of short-chain fatty acids (SCFA) were significantly higher in the liver, serum, and faeces of diabetic rats after treating with PSG-1 for 4 weeks. These results suggest that the improvement of PSG-1 on liver function in type 2 diabetic rats may be due to its antioxidant effects, SCFA excretion in the colon from PSG-1, and regulation of hepatic glucose uptake by inducing GLUT4 translocation through PI3K/Akt signaling pathways.

Effect of Lactobacillus plantarum NCU116 on loperamide-induced constipation in mice

Abstract Lactobacillus plantarum, as a probiotic, has many functional properties in human intestinal tract. This study examined the effects of L. plantarum NCU116 on loperamide-induced constipation in a mouse model. Loperamide (5 mg kg−1) was injected subcutaneously to induce constipation. Animals were divided to five groups: normal group, constipation group, constipation plus three doses of L. plantarum NCU116 groups (NCU116-L, 107 CFU/mL; NCU116-M, 108 CFU/mL; NCU116-H, 109 CFU/mL; respectively). Mice were treated with the probiotic for 15 d to assess the anti-constipation effects. Fecal parameters, intestinal transit ratio and the production of fecal short chain fatty acids, histological of colon and immunohistochemical in colonic interstitial cells of Cajal (ICC) by c-kit were all improved in L. plantarum NCU116-treated mice as compared to the constipation group. These results demonstrate that L. plantarum NCU116 enhanced gastrointestinal transit and alleviated in mice with loperamide-induced constipation.

Bidirectional Estrogen-Like Effects of Genistein on Murine Experimental Autoimmune Ovarian Disease

This study was to investigate the bidirectional estrogen-like effects of genistein on murine experimental autoimmune ovarian disease (AOD). Female BALB/c mice were induced by immunization with a peptide from murine zona pellucida. The changes of estrous cycle, ovarian histomorphology were measured, and the levels of serum sex hormone were analyzed using radioimmunoassay. Proliferative responses of the ovary were also determined by immunohistochemistry. Administration of 25 or 45 mg/kg body weight genistein enhanced ovary development with changes in serum sex hormone levels and proliferative responses. Meanwhile, the proportions of growing and mature follicles increased and the incidence of autoimmune oophoritis decreased, which exhibited normal ovarian morphology in administration of 25 or 45 mg/kg body weight genistein, while a lower dose (5 mg/kg body weight genistein) produced the opposite effect. These findings suggest that genistein exerts bidirectional estrogen-like effects on murine experimental AOD, while a high dose (45 mg/kg body weight) of genistein may suppress AOD.