Abstract

BackgroundType 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease, and the prevalence has increased significantly in recent decades to epidemic proportions in China. Individually, fenugreek (Trigonella foenum graecum) seed, mulberry (Morus alba L.) leaf and American ginseng (Panax quinquefolius) root can improve glycemia in various animal models and humans with impaired glucose metabolism and T2DM. The aim of this study was to design an optimized botanical formula containing these herbal extracts as a nutritional strategy for the prevention of insulin resistance and T2DM.MethodsCell-free α-amylase and α-glucosidase enzyme assays were used to determine inhibitory potential of extracts. Glucose uptake was examined in differentiated human adipocytes using radiolabeled 2-deoxyglucose. Male Sprague Dawley rats were divided and glycemia balanced into 5 groups: two controls (naïve and model) and three doses of the botanical test formula containing standardized fenugreek seed, mulberry leaf and American ginseng extracts (42.33, 84.66 and 169.33 mg/kg BW). Insulin resistance and T2DM was induced by feeding animals a high fat diet and with an alloxan injection. Glucose tolerance was examined by measuring serum glucose levels following an oral glucose load.ResultsFenugreek seed and mulberry leaf dose dependently inhibited α-amylase (IC50 = 73.2 μg/mL) and α-glucosidase (IC50 = 111.8 ng/mL), respectively. All three botanical extracts improved insulin sensitivity and glucose uptake in human adipocytes, which lead to the design of an optimized botanical test formula. In a rat model of insulin resistance and T2DM, the optimized botanical test formula improved fasting serum glucose levels, fasting insulin resistance and the development of impaired glucose tolerance. The reduction in epididymal adipose tissue GLUT4 and PDK1 expression induced by high fat diet and alloxan was blunted by the botanical test formula.ConclusionsA novel botanical formula containing standardized extracts of mulberry leaf, fenugreek seed and American ginseng at a ratio of 1:1.3:3.4 prevented the development of insulin resistance, impaired glucose tolerance and T2DM. Given the rising need for effective non-drug targeting of insulin resistance and progression to T2DM, complementary and alternative nutritional strategies without intolerable side effects could have meaningful impact on metabolic health and diabetes risks.

Highlights

  • Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease, and the prevalence has increased significantly in recent decades to epidemic proportions in China

  • Mulberry leaf and American ginseng have individually been reported to be efficacious in improving glucose homeostasis, our objective was to design a unique botanical formula containing a combination of standardized fenugreek seed, mulberry leaf and American ginseng extracts that had the potential to synergize each other in the prevention of insulin resistance and T2DM

  • Mulberry leaf and a Western blot Epididymal adipose tissue was homogenized in lysis buffer, which was comprised of 50 mM Tris-HCl, 0.1% sodium dodecyl sulfate (SDS), 2 M phenylmethylsulfonyl fluoride, 10 g/mL leupeptin (Amresco Solon, OH) and boiled in 5× loading buffer (Beyotime Shanghai, China)

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Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease, and the prevalence has increased significantly in recent decades to epidemic proportions in China. Fenugreek (Trigonella foenum graecum) seed, mulberry (Morus alba L.) leaf and American ginseng (Panax quinquefolius) root can improve glycemia in various animal models and humans with impaired glucose metabolism and T2DM. Hundreds of plants either individually or as recipes have been claimed to prevent and or treat T2DM [11]. Of these plants, fenugreek (Trigonella foenum graecum) seed, mulberry (Morus alba L.) leaf and American ginseng (Panax quinquefolius) root are frequently reported as efficacious (see reviews) [12,13,14]

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