Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder which has become a major risk to the health of humankind, as its global prevalence is increasing rapidly. Currently available treatment options in modern medicine have several adverse effects. Thus, there is an urgent need to develop alternative cost-effective, safe, and active treatments for diabetes. In this regard, medicinal plants provide the best option for new therapeutic remedies desired to be effective and safe. Recently, we focused our attention on drimane sesquiterpenes as potential sources of antimalarial and antidiabetic agents. In this study, iso-mukaadial acetate (Iso) (1), a drimane-type sesquiterpenoid from the ground stem bark of Warburgia salutaris, was investigated for glucose uptake enhancement in the L6 rat myoblast cell line. In vitro assays with L6 skeletal muscle cells were used to test for cytotoxicity, glucose utilisation, and western blot analysis. Additionally, the inhibition of carbohydrate digestive enzymes and 1,1-diphenyl-2- picrylhydrazyl (DPPH) scavenging activity were analysed in vitro. The cell viability effect of iso-mukaadial acetate was the highest at 3 µg/mL with a percentage of 98.4. Iso-mukaadial acetate also significantly and dose-dependently increased glucose utilisation up to 215.18% (12.5 µg/mL). The increase in glucose utilisation was accompanied by enhanced 5’ adenosine monophosphate-activated protein kinase (AMPK)and protein kinase B (AKT) in dose-dependent manner. Furthermore, iso-mukaadial acetate dose-dependently inhibited the enzymes α-amylase and α-glucosidase. Scavenging activity against DPPH was displayed by iso-mukaadial acetate in a concentration-dependent manner. The findings indicate the apparent therapeutic efficacy of iso-mukaadial acetate isolated from W. salutaris as a potential new antidiabetic agent.

Highlights

  • IntroductionBiomolecules 2019, 9, 520 both [1,2]

  • Diabetes mellitus is a metabolic disorder characterized by inappropriate hyperglycaemia, which is stimulated by several factors such as inadequate insulin secretion, insulin inaction, and at times, Biomolecules 2019, 9, 520; doi:10.3390/biom9100520 www.mdpi.com/journal/biomoleculesBiomolecules 2019, 9, 520 both [1,2]

  • Our results showed that iso-mukaadial acetate activated AKT when cells were cultured in Activate the AMPK

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Summary

Introduction

Biomolecules 2019, 9, 520 both [1,2] This disorder prevails worldwide, with its occurrence increasing at an alarming rate [3]. The treatment options for DM are based on parental insulin and oral antidiabetic drugs These hypoglycaemic agents include biguanides, sulphonylureas, and other drugs like acarbose [4]. Side effects that have been reported from the use of these drugs include hepatorenal disturbances, hypoglycaemic coma [5], acute hepatitis, diarrhoea, and abdominal pain [6]. The effectiveness of these drugs may be lost after prolonged usage [7]. There has been a rise in medicinal plant research, studying potential antidiabetic action [5]

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