Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION: SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

Efficacy of quercetin, oleanolic acid, icariin on apoptosis and mitogen-activated protein kinases signaling pathways in hippocampal neurons of Sprague-Dawley rats cultured with high glucose medium.

OBJECTIVE: To investigate the effect of quercetin, oleanolic acid, icariin and their compatibility on the apoptosis of hippocampal neurons of Sprague-Dawley (SD) rats cultured with high glucose medium and the possible mechanism. METHODS: The extracts were purchased from China Food and Drug Control Institute and Sellect. Hippocampus was obtained from newborn 24 h SD rats. After culturing the hippocampus in different medium for 72 h, flow cytometry was used to detect the apoptosis of hippocampal neurons, and Western blot was utilized to test the expressions of p-p38, p38, p-c-Jun N-terminal kinase (JNK) and JNK. RESULTS: Compared with the control group (CG), the neuronal apoptosis rate and the ratios of p-p38/p38 and p-JNK/JNK were significantly increased in the high glucose group (GG) (P < 0.01); Compared with the GG, the apoptosis rate and the ratios of p-p38/p38 and p-JNK/JNK were significantly decreased in other drug groups (P < 0.01); Compared with the monomer groups respectively, the apoptosis rate and the ratios of p-p38/p38 and p-JNK/JNK in the two-drug groups and the three-drug group all decreased (P < 0.01); Compared with the two-drug groups, the neuronal apoptosis rate and the ratio of p-JNK/JNK of the three-drug group decreased (P < 0.05). CONCLUSION: Under the condition of high glucose, the quercetin, oleanolic acid and icariin can alleviate the apoptosis of hippocampus neurons, reduce the phosphorylation of p38 and JNK in p38 mitogen-activated protein kinases and JNK signaling pathway. And the efficacy of the three drugs in combination with each other can be strengthened.

Effects of Bushen Huoxue formula on the learning and memory function and the cerebral neurotransmitters in diabetic mice.

OBJECTIVE: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice. METHODS: Forty ICR mice were randomized into the normal control group, model group, Nimotop group and Chinese medicine group, 10 mice in each group. Tail intravenous injection of alloxan was applied to prepare diabetic model. Four weeks later, intragastric administration of Bushen Huoxue Formula for the Chinese medicine group, Nimotop for the Nimotop group, and isometric distilled water for the other two groups were respectively given for 8 weeks. The changes in the blood sugar level were observed; the learning and memory function was detected by Morris labyrinth test; and the contents of norepinephrine (NE), dopamine (DA), 5-hydroxyltryptamine (5-HT) and 5-hydroxyl indole acetic acid (5-HIAA) in cerebral cortex were determined in mice of all the groups. RESULTS: The blood sugar levels in the diabetic model mice significantly increased as compared with those of the normal control group determined 72 h and 12 weeks later (P < 0.05 or P < 0.01). Latencies for Morris labyrinth test in the Nimotop group and the Chinese medicine group were significantly shortened as compared with that in the model group (P < 0.01). The contents of cortical NE in the Chinese medicine group was significantly higher than that in the model group (P < 0.01). CONCLUSION: Bushen Huoxue Formula can improve the learning and memory function in the diabetic mice, and the mechanism is possibly related with change of the cortical NE content.

[Effect of Ningzhi capsule on blood lipid spectrum in type 2 diabetes mellitus patients complicated with hyperlipidemia].

OBJECTIVE: To observe the effect of Ningzhi Capsule (NZC) on blood lipid spectrum in type 2 diabetes mellitus patients complicated with hyperlipemia (DM-HL). METHODS: Adopting randomized, parallel and controlled trail method, a total of 70 DM-HL patients of qi-yin deficiency and phlegm-blood stagnant syndrome type were randomized into two groups. The original medication for lowering blood sugar and blood pressure was unchanged, the trial group received oral administration of NZC 5 tablets, 3 times a day, while the control group received Lipanthgl or Simvastatin depending on their different constituents of blood lipids. After 6 months of treatment, sixty subjects completed the trail while two patients dropped out due to side effect and 8 patients lost follow-up (4 in each group). Levels of blood lipids, blood routine, liver and kidney function and symptoms in patients were detected and compared. RESULTS: After treatment, levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), apoprotein B, and lipoprotein a (LPa) lowered, while levels of high-density lipoprotein (HDL-C) and apoprotein A raised in the trial group as compared with those before treatment (P < 0.05, P < 0.01), but showed no difference between the two groups after treatment except HDL level (P > 0.05). Scores of symptoms were also lowered significantly in the trial group (P < 0.01). In the observation period, no abnormal findings in blood and urine routine examination as well as in liver and renal function were found. CONCLUSION: NZC could lower the blood lipid spectrum and improve the TCM symptoms in DM-HL patients without any adverse reaction.