Hydro-alcoholic extract of Morus nigra reduces fasting blood glucose and HbA1c% in diabetic patients, probably via competitive and allosteric interaction with alpha-glucosidase enzyme; a clinical trial and in silico analysis.

OBJECTIVES: 1-Deoxynojirimycin (1-DNJ), the main active component found in Morus nigra (black mulberry) is reported to be effective in controlling diabetes. We have evaluated the effect of hydro-alcoholic extract of M. nigra leaves on the fasting blood glucose (FBS) and hemoglobin A1c% (HbA1c%) in diabetic patients. Furthermore, we compared the interaction of 1-DNJ and glucose molecules with the alpha-glucosidase enzyme, which has a critical role in the lysis of glucose-based polymers in human cells. METHODS: 4% hydro-alcoholic extract was prepared from black mulberry leaves. Patients in treatment (n=50) and control (n=50) groups received 3 mL extract or placebo in water, respectively, and three times a day. Fasting blood glucose and HbA1c% were evaluated before and after three months of evaluation. Potential binding sites of 1-DNJ or glucose on the enzyme glucosidase found by docking study. Docking scores were obtained using an energy minimization method by Molegro Virtual Docker software. The Mean ± SD of each variable was compared between groups at the 95% significant level. RESULTS: Age mean ± SD was equal to 54.79 ± 9.203 (38-69) years. There was no significant difference between intervention and placebo groups considering FBS (p=0.633) but was for HbA1c% (p=0.0011), before treatment. After three months, both FBS and HbA1c% were significantly reduced in patients under mulberry leaves extract-treatment. FBS changed was from 182.23 ± 38.65 to 161.23 ± 22.14 mg/dL in treatment group (p<0.001) and from 178.45 ± 39.46 to 166.23 ± 29.64 mg/dL in control group (p<0.001). HbA1c was changed from 7.23 ± 0.25 to 6.13 ± 0.61% in treatment group (p<0.001) and from 7.65 ± 0.85 to 7.12 ± 0.33% in control group (p=0.854). Docking results showed that 1-DNJ binds more efficiently, and with a significant score than glucose, to human alpha-glucosidase. CONCLUSIONS: This clinical trial and virtual analysis showed that a hydro-alcoholic extract of black mulberry (M. nigra) leaf may be efficient in reducing the blood glucose and HbA1c% in diabetic patients. Furthermore, docking studies propose a competitive and allosteric regulation for herbal ingredients. Drug-development could be based on the presented idea in this report.

The effects of chromium and vitamin D3 co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial.

The current study was conducted to assess the effects of simultaneous usage with vitamin D3 and chromium picolinate (CrPic) supplementations on homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBS), hemoglobin A1c (HbA1c), tumor necrosis factor-α (TNF-α), and lipid profile in type 2 diabetes mellitus (T2DM). Ninety-two patients with T2DM were randomly allocated to the following 4 groups for 4 months: (I) placebo of vitamin D3 (n = 23); (II) vitamin D3 supplement at a dose of 50 000 IU/week (n = 23); (III) CrPic supplement at a dose of 500 µg/day (n = 23); and (IV) both vitamin D3 at a dose of 50 000 IU/week and CrPic at a dose of 500 µg/day (n = 23). HOMA-IR levels increased significantly in groups I and II after the intervention. However, this increase in group I was significantly higher than that in group II after the treatment. HOMA-IR levels were controlled in groups III and IV during the intervention. TNF-α decreased significantly in groups II, III, and IV after the intervention. FBS, HbA1c, and lipid profile did not change significantly in total groups after the intervention. It seems that chromium and vitamin D3 co-supplementation are probably effective in controlling HOMA-IR by decreasing TNF-α in T2DM. Novelty Chromium alone and/or in simultaneous pretreatment with vitamin D3 is more effective than vitamin D3 in controlling HOMA-IR in T2DM. Chromium and vitamin D3 alone and/or in simultaneous pretreatment decrease TNF-α in T2DM.