Effects of Astragalus polysaccharide on the erythroid lineage and microarray analysis in K562 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus polysaccharide (APS), obtained from Astragalus membranaceus, displays a range of activities in many systems, including the promotion of immune responses, anti-inflammation, and the protection of vessels. It possesses potent pharmacological activity on differentiation to the erythroid lineage. AIM OF THE STUDY: To investigate the effects of APS on the erythroid differentiation and the mechanism of action by microarray analysis in K562 cells. MATERIALS AND METHODS: Benzidine staining, semi-quantitative RT-PCR, Western blot and microarray methods were used to survey the effects of APS on inducing erythroid differentiation and the changes of gene expression profile in K562 cells. RESULTS: Of the 13.2% positive cells detected by benzidine staining, the induction was the highest with 200 microg/ml APS on 72h. Ggamma-mRNA expression and fetal hemoglobin synthesis were significantly up-regulated. Microarray analysis showed that 31 genes were up-regulated and 108 genes were down-regulated. These differential expression genes generally regulate protein binding, cellular metabolic process, the cell proliferation, and transcriptional activator activity. The gamma-globin gene was up-regulated, the genes related with erythroid differentiation such as LMO2, Runx1 and GTF2I were up-regulated, while Bklf, Eklf, EPHB4 and Sp1 were down-regulated. CONCLUSIONS: Our studies indicate that APS indicate potent activities on the erythroid differentiation by modulating genes of LMO2, Klf1, Klf3, Runx1, EphB4 and Sp1, increasing gamma-globin mRNA expression and fetal hemoglobin synthesis in K562 cells.

Protective role of supplement with foreign Bifidobacterium and Lactobacillus in experimental hepatic ischemia-reperfusion injury.

BACKGROUND AND AIM: Intestinal microflora play a crucial role in some severe liver diseases. The purpose of this study was to evaluate the effects of a Lactobacillus strain and a Bifidobacterium strain on ischemia-reperfusion (I/R) liver injury. METHODS: Rats were divided into six groups. Each group received either Bifidobacterium Catenulatum ZYB0401; Lactobacillus Fermentum ZYL0401; a mixture of these two bacterial strains; gentamicin; or saline by daily gavage for 7 days. On the sixth day, all rats, except those in the control group, were subjected to 20 min of liver ischemia. After 22 h of hepatic reperfusion, liver enzymes and histology, malondialdehyde (MDA), superoxide dismutase (SOD), endotoxemia, serum tumor necrosis factor-alpha (TNF-alpha), intestinal bacteria, intestinal mucosal ultrastructure, and bacterial translocation were studied. RESULTS: All administered bacteria increased intestinal Bifidobacterium and Lactobacillus, decreased endotoxemia (P < 0.01), alanine aminotransferase (ALT) (P < 0.01), and markedly ameliorated liver histology and intestinal mucosal ultrastructure. Only rats treated with Bifidobacterium Catenulatum ZYB0401 and Lactobacillus Fermentum ZYL0401 showed reduced incidence of bacterial translocation to the kidney (P < 0.05), associated with decreased serum TNF-alpha and liver MDA (P < 0.05) and increased liver SOD (P < 0.05) compared to the I/R group. Gentamicin decreased almost all kinds of intestinal bacteria (P < 0.01) and decreased ALT (P < 0.01) and serum TNF-alpha, but failed to reduce both endotoxemia and the incidence of bacterial translocation and had no effects on liver MDA and SOD. CONCLUSION: Bifidobacterium Catenulatum ZYB0401 in combination with Lactobacillus Fermentum ZYL0401 could be useful in restoring intestinal microflora and in preventing liver injury in hepatic I/R of rats.

Effects of Salvia miltiorrhiza on intestinal microflora in rats with ischemia/reperfusion liver injury.

BACKGROUND: Hepatic ischemia/reperfusion injury may induce intestinal microflora imbalance. Salvia miltiorrhiza is effective in promoting blood circulation and counteracting peroxidation in tissues. The aim of the present study was to determine the effects of Salvia miltiorrhiza on intestinal microflora, endotoxemia, and bacterial translocation in rats with hepatic I/R injury. METHODS: Sprague-Dawley rats in specific pathogen free grade were divided into 3 groups: group I(n=6) for sham operation; groups II(n=10) and III(n=7) for liver ischemia for 20 minutes and reperfusion for 22 hours. Group III was also pretreated with 4 ml/day of Salvia miltiorrhiza solution (250 mg/kg) by daily gavage for 7 days. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and superoxide dismutase(SOD) in liver tissues, serum endotoxin, intestinal bacterial counts, intestinal mucosal histology and bacterial translocation were studied. RESULTS: The levels of ALT, AST, plasma endotoxin and MDA in liver tissues were decreased more markedly in group III (57.57+/-18.08 U/L, 147.57+/-40.84 U/L, 0.42+/-0.144 EU/ml and 0.52+/-0.19 nmol/mg-prot respectively) in group II(122.8+/-80.12 U/L, 295.9+/-216.92 U/L, 0.80+/-0.262 EU/ml and 0.72+/-0.12 nmol/mg-prot; P<0.05-0.01 respectively). Liver SOD activity was increased more significantly in group III (318.47+/-64.62 U/mg-prot) than in group II(240.76+/-63.67 U/mg-prot, P<0.05). The counts of Bifidobacteria and Bacteroides increased more significantly in group III than in group II, but were similar to those in group I. Bacterial translocation to the kidney in group II was 50%(5/10), whereas no bacterial translocation to the kidney occurred in the other two groups (P<0.01). Ileal mucosal structure was markedly ameliorated in group III as compared with group II. CONCLUSIONS: Salviae miltiorrhiza could partially restore intestinal microflora balance, improve intestinal mucosal integrity, and reduce bacterial translocation and plasma endotoxin in rats with hepatic ischemia/reperfusion injury.