Anti-diabetic effects of the fraction of alkaloids from Ramulus Mori, an innovative Sangzhi alkaloids as an α-glucosidase inhibitor / 药学学报

Sangzhi alkaloids (SZ-A) are derived from traditional Chinese medicine Ramulus Mori, serving well as an innovative antidiabetic drug, due to α-glucosidase inhibition. To evaluate the potency of glucosidase inhibitory effect of SZ-A, the enzyme-based screening platforms, including sucrase, maltase and amylase were established, and IC50 was calculated. The effects of SZ-A on postprandial blood glucose at a single dose, oral sucrose, starch and glucose loading were determined in normal ICR mice and alloxan-induced hyperglycemic mice. To confirm the anti-diabetic effects of SZ-A on glucose and lipid metabolism after long-term administration, the postprandial and fasting blood glucose, serum insulin, urinary glucose levels, glycosylated serum proteins and blood lipid levels were determined in high-fat fed C57 obese mice (pre-diabetic HFC57 mice) and diabetic rats induced by streptozotocin (STZ). The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. We found that SZ-A exhibited a significant inhibitory effect on the sucrase and maltase. SZ-A showed no effect on amylase. In normal ICR mice and alloxan-induced hyperglycemic mice, SZ-A at a single dose significantly delayed and reduced the peak of blood glucose after sucrose or starch loading, but showed no effect on the increase of blood glucose after glucose loading. In STZ diabetic rats, SZ-A significantly reduced the postprandial or fasting blood glucose levels, glycosylated serum proteins and urinary glucose. SZ-A also reduced serum triglyceride (TG) and cholesterol (TC) levels after 3 weeks of treatment. SZ-A ameliorated the postprandial blood glucose or the fasting blood glucose elevation, and reduced the incidence of hyperglycemia in HFC57 mice. SZ-A decreased the basal insulin level, improved insulin sensitivity, and ameliorated glucose intolerance in pre-diabetic HFC57 mice. Our results indicated that SZ-A had a novel inhibitory activity on α-glucosidase, especially on disaccharidases. SZ-A at a single dose significantly reduced the peak of blood glucose elevation and delayed the increase of blood glucose in normal and diabetic mice after disaccharide and polysaccharide loading. Long-term SZ-A treatment improved glucose and lipid metabolic profiles by delaying carbohydrate absorption from the intestine and reduced the postprandial blood glucose levels in both pre-diabetic and diabetic animal models. Therefore, SZ-A application may display a beneficial role in preventing the development and complications of diabetes.

Association of Helicobacter pylori with Elevated Blood Ammonia Levels in Cirrhotic Patients: A Meta-Analysis

PURPOSE: The association between Helicobacter pylori (H. pylori) and blood ammonia levels in cirrhotic patients is controversial. We aimed to clarify this controvercy by performing a meta-analysis of published studies. MATERIALS AND METHODS: We searched PubMed, EMBASE and Cochrane library for studies which explored the association between H. pylori and blood ammonia levels in cirrhotic patients before May 2012. Six cohort studies involved in 632 H. pylori positive and 396 H. pylori negative cirrhotic patients were eligible for our analysis. The summary estimates were presented as standard means differences (SMD) and 95% confidence intervals (CI) from individual studies. RESULTS: Overall, there was significant association between H. pylori infection and the elevated blood ammonia levels in cirrhotic patients (SMD=0.34, 95% CI=0.21-0.47, I2=42.1%). Sensitivity analysis further confirmed this association. Subgroup analysis showed that the association was found only in Asian ethnicity, but not in Caucasian ethnicity. CONCLUSION: H. pylori infection is associated with elevated blood ammonia levels in cirrhotic patients, and more large scale studies and stratify analysis are warranted in order to further evaluate this association.

Ameliorations of pioglitazone on insulin resistance in spontaneous IGT-OLETF rats / 药学学报

<p><b>AIM</b>To investigate the ameliorations of pioglitazone, a member of the thiazolidinedione group of antidiabetic agents, on insulin resistance in spontaneous OLETF rats with impaired glucose tolerance (IGT-OLETF).</p><p><b>METHODS</b>One group of IGT-OLETF rats was orally administered pioglitazone at the dose of 20 mg x kg(-1) (qd) for 2 weeks. Another group was given the same volume of solvent as control. Glucose tolerance and insulin tolerance were tested, and blood glucose concentrations, insulin levels and lipids in serum, liver and muscle were determined. Insulin sensitive index (ISI) was calculated by the reciprocal of fasting blood glucose times fasting insulin.</p><p><b>RESULTS</b>Pioglitazone was shown to markedly enhance the glycemic response to exogenous insulin (0. 4 x kg(-1), sc) in the model. The falls of blood glucose at 40 and 90 min in the insulin tolerance test were augmented by 70% and 158% in the treated group than the control. The serum insulin levels were significantly decreased and the ISI nearly normalized after treatment. Pioglitazone also lowered the serum TG and FFA levels and the lipids in liver and muscle. No effect was found on the expression of leptin in epididymal adipose tissues and on the activity of GFAT, a key enzyme in hexosamine biosynthesis pathway (data were not shown).</p><p><b>CONCLUSION</b>Pioglitazone can improve the insulin resistance state in IGT-OLETF rats. Correction of lipid disorder may be associated with it.</p>

Effects of conjugated linoleic acid on obese MSG mice with insulin resistance / 药学学报

<p><b>AIM</b>To study the effect of conjugated linoleic acid (CLA) on obese MSG mice with insulin resistance.</p><p><b>METHODS</b>About four months old, obese MSG mice with insulin resistance were divided into control, CLA and rosiglitazone groups and drugs were administrated ig once a day. Body weights were recorded regularly, insulin and glucose tolerance were tested. In addition, serum insulin and TNF-alpha concentrations in serum and fat tissues were determined.</p><p><b>RESULTS</b>CLA was shown to reduce the body weight and fat weight in MSG mice, but can not improve the abnormal insulin and glucose tolerance in these mice. Indeed, the serum insulin and TNF-alpha concentrations in the fat tissues of the group treated with CLA were higher than those in the models and the insulin sensitivity index was significantly lower than that in the model mice.</p><p><b>CONCLUSION</b>CLA can reduce the body weight of MSG mice, but can not improve the insulin resistance in these mice.</p>

Experimental treatment of complications in alloxan diabetic rats with alpha-glucosidase inhibitor from the Chinese medicinal herb ramulus mori / 药学学报

<p><b>AIM</b>To assess the effects of the alpha-glucosidase inhibitor Sangzhi (Ramulus mori, SZ) on the relief of diabetic symptoms of hyperglycemia and the prevention of its late complications in alloxan diabetic rats with high-calorie chow.</p><p><b>METHODS</b>The aqueous extract of Sangzhi was given orally to alloxan diabetic rats for 15 days. The hyperglycemic symptoms were observed. The blood glucose, lipid levels and the nephrotic representations were measured.</p><p><b>RESULTS</b>When alloxan diabetic rats on high-calorie chow were treated with SZ, the hyperglycemic symptoms were improved, the blood lipid levels were improved, the ratio of kidney over body weight and the blood N-acetyl-beta-D-glucosaminidase (NAG) activity were lowered. The degree of renal pathological changes was significantly reduced.</p><p><b>CONCLUSION</b>SZ may be useful for treating diabetes and its complications.</p>