• Introducing a terrestrial Myxobactreium as a potential source of anti-diabetic agents
  • Fatemeh Mohammadi panah,1,* Mohammad Hossain Nikzad,2 Fatemeh Saadatpour,3 Fatemeh Salimi,4
    1. Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran
    2. 1 Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran
    3. Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran
    4. Department of Cellular and Molecular Biology, School of Biology, Damghan University, Damghan, Iran


  • Introduction: Diabetes is a common metabolic disease characterized by abnormally high plasma glucose levels, leading to major complications, such as diabetic neuropathy, retinopathy, and cardiovascular diseases. The increasing prevalence of hyperglycemia and negative side effect implications of commercial anti-diabetic medicines have increased the demands to discover new anti-diabetic drugs. The Myxobacteria are the most promising microbial sources in drug discovery. Two commercial drugs of epothilones and gephyronic acid, and also Cystobactamid, Eliamid, Icumazol, Nannocystin, Sulfangolid are some examples of active compounds produced by Myxobacteria [1]. The unique structural diversity of their secondary metabolites offer them as proper drug discovery resources [2]. The aim of the present study was the evaluation of Afghanistan Myxobacterial isolates for the production of anti-diabetic secondary metabolites.
  • Methods: Myxobacterial isolates were isolated from soil samples collected from different parts of Afghanistan. In order to isolate the active metabolites, 10 distinct isolates were separately inoculated in the fermentation medium and their secondary metabolites were extracted and concentrated from the supernatant and cell mass using a solvent-based approach. To investigate the anti-diabetic activity of obtained extracts, the inhibitory effect of these metabolites was assessed on alpha-glycosidase, alpha-amylase, glucose uptake and protein glycation using in-vitro assays at a concentration of 400µg/ml of the extracts. Also, the cytotoxicity effect of crud extracts was evaluated using the Human Red Blood Cell (HRBC) lysis assay and Brine Shrimp Test (BST) test at concentrations of 25, 50 and µg/ml.
  • Results: Based on in-vitro assays, it was found that the extracts obtained from strains UTMC 4538 and UTMC 4530 showed higher alpha-glycosidase inhibitory effect in comparison to acarbos as a positive control with 29.5% and 23.0%, respectively. Also obtained extracts of UTMC 4532 and UTMC 4530 showed high inhibitory activity on alpha-amylase with 24.5 % and 15.87%, in comparison to acarbos as a positive control. The extract of UTMC 4535 exhibited a notable promoting effect of 55.2% on glucose uptake in yeast cells. Furthermore, the extract of UTMC4530 showed inhibition on the formation of carbonyl groups with 8.14%, fructose amine formation with 4% and protective effect on thiol group with 38%. Based on HRBC lysis and BST tests, none of the tested extracts showed any toxic effect.
  • Conclusion: Diabetes is one of the world's greatest health problems. It has been estimated that up to 2017 about 8.8% of people aged between 20-79 were involved in diabetes. This percentage in Iran, based on the statistics of the Diabetes Association, is 12%. One of the effective management of diabetes mellitus is to retard the inhibition of carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase, in the digestive organs. Since various structures with antibiotic and enzymatic inhibitory activities are derived from Myxobacteria, these bacteria were selected in this study as the candidates for the discovery of new drugs for the treatment of diabetes. The obtained results showed that the extract of UTMC 4530 contains active compounds with inhibition effect on α-glucosidase, α-amylase and glucose uptake and also protein glycation. The current in vitro experiments suggests that selected extract is confirmed as a modulator of multiple targets including enzymatic and non-enzymatic pathways involved in diabetes. Therefore, it could contain compounds with a potential therapeutic effect on diabetes. Therefore, the extract obtained from this isolate could be a valuable source of new anti-diabetic discovery
  • Keywords: Drug discovery, Bioactive metabolites, Myxobacteria, Anti-diabetic drugs