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

Abstract

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.

Effect of mulberry leaf or mulberry leaf extract on glycemic traits: a systematic review and meta-analysis

“…The clinical trial and virtual analysis showed that a hydro-alcoholic extract of black mulberry ( M. nigra ) leaf may be efficient in decreasing FPG and HbA1c in diabetic patients. 60 The study conducted with 37 adult participants proved that the difference in the positive incremental area under the curve ((pIAUC) for glucose concentration over 120 minutes) for 125, 250, and 500 mg mulberry extract compared with placebo was −6.1% ( p = 0.316), −14.0% ( p = 0.022), and −22.0% ( p < 0.001), respectively. 61 1-DNJ is an effective inhibitor of α-glucosidase, which is an enzyme that breaks down starch and other disaccharides into glucose.…”

Applications of Mulberry Leaves: An Overview

“…DNJ is a potential antihyperglycaemic compound in mulberry leaves as it inhibits glucosidase, suppress abnormally high level of blood glucose and prevent diabetes mellitus (Ramappa et al, 2020;Tang et al, 2023). Furthermore, glucose and DNJ are similar in structures that is why DNJ blocks the main active sites of glucose degrading enzymes; so inhibits the carbohydrates digestion and absorption (Momeni et al, 2021;Mohamed et al, 2023). DNJ is known as a cofactor and help in controlling postprandial blood glucose; also helps in degrading the oligosaccharides and starch to monosaccharides before their absorption (Liu et al, 2015).…”

The role of selected nutraceuticals in management of prediabetes and diabetes: An updated review of the literature

“…In the study of Momeni et al (2021) 1 tablet/day white mulberry 50 mg, I. paraguariensis 1,000 mg, and chromium picolinate 100 μg 3 months FPG, PPG, HbA 1c , and HOMA index decrease M value increase Derosa et al (2021) Abbreviations: 1,5AG, 1,5-anhydroglucitol; FPG, fasting plasma glucose; FPI, fasting plasma insulin; GA, glycated albumin; HbA 1c , glycated hemoglobin; HOMA-IR, homeostatic model assessment of insulin resistance; iAUC, incremental area under the curve; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test; PPG, post-prandial plasma glucose; PPI, post-prandial plasma insulin; SMBG, self-monitoring blood glucose; T2DM, type 2 diabetes mellitus.…”

“…In the study of Momeni et al ( 2021 ) 100 T2DM patients were treated with 3 ml of 4% hydroalcoholic extract of M. nigra leaves or placebo in water, thrice a day, for 3 months. It has been observed that the supplement significantly decreased FPG (−21.00 mg/dl, −11.52%, p < .001) and HbA 1c (−1.10%, −15.21%, p < .001) compared to baseline values (Momeni et al, 2021 ).…”