1-deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice.

We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance tests and labeled (13)C6-glucose uptake assays suggested that DNJ inhibited intestinal glucose absorption in intestine. We also showed that DNJ down-regulated intestinal SGLT1, Na(+)/K(+)-ATP and GLUT2 mRNA and protein expression. Pretreatment with DNJ (50 mg/kg) increased the activity, mRNA and protein levels of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in hepatic cells and in vitro tests with purified enzymes indicated that the increased activity of glucose glycolysis enzymes was resulted from the relative increase in protein expression, rather than from direct enzyme activation. These results suggest that DNJ inhibits intestinal glucose absorption and accelerates hepatic glucose metabolism by directly regulating the expression of proteins involved in glucose transport systems, glycolysis and gluconeogenesis enzymes.

Hybrid of 1-deoxynojirimycin and polysaccharide from mulberry leaves treat diabetes mellitus by activating PDX-1/insulin-1 signaling pathway and regulating the expression of glucokinase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in alloxan-induced diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: 1-Deoxynojirimycin (DNJ) discovered from mulberry trees has been reported to be a potent inhibitor of intestinal α-glycosidases (sucrase, maltase, glucoamylase), and many polysaccharides were useful in protecting against alloxan-induced pancreatic islets damage through their scavenging ability. This study was aimed to evaluate the therapeutic effect and potential mechanism(s) of the hybrid of DNJ and polysaccharide (HDP) from mulberry leaves on alloxan-induced diabetic mice. MATERIALS AND METHODS: Daily oral treatment with HDP (150 mg/kg body weight) to diabetic mice for 12 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test was performed after 4 and 8 weeks, biochemical values were measured using assay kits and gene expressions were investigated by RT-PCR. RESULTS: A significant decline in blood glucose, glycosylated hemoglobin, triglyceride, aspartate transaminase and alanine transaminase levels and an evident increase in body weight, plasma insulin level and high density lipoprotein were observed in HDP treated diabetic mice. The polysaccharide (P1) showed a significant scavenging hydroxyl radicals and superoxide anion radical effects in vitro, which indicated that P1 could protect alloxan-induced pancreatic islets from damage by scavenging the free radicals and repaired the destroyed pancreatic ß-cells. Pharmacokinetics assay showed that DNJ could be absorbed from the gastrointestinal mucosa and diffused rapidly into the liver, resulted in postprandial blood glucose decrease and alleviated the toxicity caused by sustained supra-physiological glucose to pancreatic ß-cells. RT-PCR results indicated that HDP could modulate the hepatic glucose metabolism and gluconeogenesis by up/down-regulating the expression of rate-limiting enzymes (glucokinase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in liver and up-regulating the pancreatic and duodenal homeobox factor-1 (PDX-1), insulin-1 and insulin-2 expressions in pancreas. CONCLUSION: These findings suggested that HDP has complimentary potency to develop an antihyperglycemic agent for treatment of diabetes mellitus.

Anti-tumor effects of proteoglycan from Phellinus linteus by immunomodulating and inhibiting Reg IV/EGFR/Akt signaling pathway in colorectal carcinoma.

Proteoglycan (P1) purified from Phellinus linteus has been reported to have anti-disease activities. The objectives of our research were to determine the anti-tumor effect and possible mechanisms of P1 on human cancer cells. Cell inhibition assay showed that P1 has an antiproliferative effect on HepG2, HT-29, NCI-H 460 and MCF-7 human colon cancer cells, especially it was very effective in inhibiting HT-29 cells. When HT-29-bearing mice were treated with P1(100mg/kg), there was relative increase in spleen and thymus weights, the plasmatic pIgR and IgA levels were significantly increased, also there was a notable decrease in plasmatic PGE2, Reg IV, EGFR and Akt concentrations measured by ELISA. RT-PCR analysis suggested that P1-induced HT-29 apoptosis appeared to be associated with a decrease in the levels of expression of Reg IV and EGFR. These results suggest that P1 might have two potential roles in treating cancer; it acts as an immunopotentiator partly through protecting T cells from escaping PGE2 attack and enhancing the mucosal IgA response, and as a direct inhibitor by disrupting the Reg IV/EGFR/Akt signaling pathway.

Saponins from Panax japonicus protect against alcohol-induced hepatic injury in mice by up-regulating the expression of GPX3, SOD1 and SOD3.

AIMS: The purpose of this study was to investigate the possible mechanism(s) of saponins from Panax japonicus (SPJ) on alcohol-induced hepatic damage in mice. METHODS: SPJ were identified by high performance liquid chromatography-evaporative light scattering detection-mass spectrometry (LC-ELSD-MS). Non-toxic concentrations of SPJ were assayed on alcohol-induced hepatic injury in male ICR mice and human hepatic cells. The protective effects were evaluated by biochemical values, histopathological observations and the relative gene expression. Results. In vitro, SPJ showed significant hydroxyl radical scavenging capacity. In vivo, SPJ (50 mg/kg) could rectify the pathological changes of aspartate transaminase, alanine transaminase, malondialdehyde, reduced glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) caused by alcohol metabolism to normal levels except for hepatic GSH and CAT. In hepatic cells, the results were in agreement with foregoing results determined in mice after pretreatment of SPJ (100 microg/ml). RT-PCR results showed that CAT, GPX and SOD mRNA decreased by alcohol metabolism were reversed, in which GPX3, SOD1 and SOD3 could return to a normal level, but CAT, GPX1 and SOD2 mRNA were still evidently lower than the control. Histopathological observations provided supportive evidence for biochemical analyses. CONCLUSIONS: SPJ plays an important role in the protection of the structure and function of hepatic mitochondria and karyon by directly scavenging reactive oxygen species/free radicals and up-regulating the expression of antioxidant enzymes (SOD, GPX and CAT), especially to GPX3, SOD1 and SOD3.

Protective effect of sericin peptide against alcohol-induced gastric injury in mice.

BACKGROUND: Sericin peptide (SP) has shown a powerful anti-oxidant property in a host of studies. The present study was designed to investigate the possible protective effects of SP against alcohol-induced gastric lesions in mice and to explore the potential mechanisms. METHODS: Animals were randomly divided into 5 groups: control, alcohol (56%, 14.2 ml/kg), SP-treated mice (0.2, 0.4, 0.8 g/kg). Mice were pretreated with SP before administering alcohol, the concentration of ethanol in serum and urine, the contents of malondialdehyde (MDA), glutathione (GSH) and the glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD) activities in the gastric mucosa were measured, subsequently, the pathological evaluation of stomach was also observed. RESULTS: Of the animals pre-treated with SP (0.4, 0.8 g/kg), the concentration of ethanol in serum was significantly decreased, while increased in urine as compared to the alcohol-administered alone animals. Alcohol administration caused severe gastric damage as indicated by markedly increased MDA levels and decreased antioxidants, such as reduced GSH, GSH-PX and SOD in the gastric tissue while the CAT activity was not altered. On SP administration there was a reversal in these values towards normal. Histopathological studies confirmed the beneficial role of SP, which was in accordance with the biochemical parameters. CONCLUSIONS: SP could protect gastric mucosa from alcohol-induced mucosal injury. These gastroprotective effects might be due to increasing 'first-pass metabolism' in the stomach and hastening ethanol elimination directly through the urine. SP might also play an important role in the protection of the structure and function of gastric mitochondria, at least partly based on their anti-oxidant effect.

Protective effects of sericin protein on alcohol-mediated liver damage in mice.

AIMS: The purpose of this study was to investigate the protective effects of sericin protein (SP) on alcohol-induced hepatic injury in mice and the possible mechanisms. METHODS: SP (0.375, 0.75 and 1.50 g/kg body weight) was dissolved in distilled water and given to mice by gavage 1 hour before the alcohol (56% wt/vol, 14.2 ml/kg b.w.) treatment for 30 days, then blood, urine and liver were collected, processed and used for alcohol concentration mensuration, various biochemical estimations and histopathological examination. RESULTS: The concentration of alcohol evidently decreased in serum and increased in urine in SP treated mice as compared to alcohol-administered animals. Chronic alcohol administration resulted in significantly increase in the levels of transaminase (AST and ALT) and malondialdehyde (MDA) but decrease of glutathione (GSH), glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD) in the serum and liver. Hepatic triglyceride (TG) also increased. When mice ingested high doses of SP (0.75 and 1.50 g/kg b.w.) the levels of antioxidant enzymes in the serum were restored to normal. However, hepatic CAT and GSH were still below normal, although a trend of significant increases was observed in comparison with alcohol treatment group. CONCLUSIONS: The results indicated that SP was able to hasten the alcohol elimination through urine directly and enhance the ethanol oxidation rate in liver. Simultaneously, SP may exert a protective effect against lipid peroxidation by scavenging reactive oxygen species and elevating the activity of antioxidant enzymes, in consequence prevented the peroxidative deterioration of structural lipids in membranous organelles, especially mitochondria and karyon.