ABSTRACT
Diabetes is a chronic metabolic disorder characterized by persistent hyperglycaemia. It has been classified as one of the main pathologies that promotes the most severe and fatal forms of COVID-19. Although there are nowadays synthetic molecules for the regulation of this disease, their disastrous side effects still open up prospects for the search of new and healthy molecules of therapeutic interest. This study aimed at evaluating the inhibitory effect of peptides extracts produced during the cultivation of a Lactobacillus plantarum strain with probiotic properties. The peptides extracts were obtained by thermal hydrolysis of protein extracts at 70 degrees C or 80 degrees C for 10, 20 and 30 min. The potential hypoglycaemic activity was examined by testing their inhibitory effect on amylolytic enzymes. Our results showed that the studied proteins hydrolysates, when used at 0.024 mg (biomass) or 0.156 mg (growth broth), were capable of total inhibition of amylolytic enzymes activity. The biomass peptides showed higher inhibition rate compared to 95% obtained with 0.050 mg of acarbose, a potent and widely used anti-diabetic inhibitory. This study clearly shows that the investigated protein hydrolysates contain interesting inhibitory peptides that deserve further investigations for their real use as bioactive inhibitors of diabetes regulating enzymes.
ABSTRACT
Microalgae and cyanobacteria are good sources for prospecting metabolites of biotechnological interest, including glucosidase inhibitors. These inhibitors act on enzymes related to various biochemical processes; they are involved in metabolic diseases, such as diabetes and Gaucher disease, tumors and viral infections, thus, they are interesting hubs for the development of new drugs and therapies. In this work, the screening of 63 environmental samples collected in the Brazilian Amazon found activity against ß-glucosidase, of at least 60 min, in 13.85% of the tested extracts, with Synechococcus sp. GFB01 showing inhibitory activity of 90.2% for α-glucosidase and 96.9% against ß-glucosidase. It was found that the nutritional limitation due to a reduction in the concentration of sodium nitrate, despite not being sufficient to cause changes in cell growth and photosynthetic apparatus, resulted in reduced production of α and ß-glucosidase inhibitors and differential protein expression. The proteomic analysis of cyanobacteria isolated from the Amazon is unprecedented, with this being the first work to evaluate the protein expression of Synechococcus sp. GFB01 subjected to nutritional stress. This evaluation helps to better understand the metabolic responses of this organism, especially related to the production of inhibitors, adding knowledge to the industrial potential of these cyanobacterial compounds.
ABSTRACT
The dried fruits of Amomum tsao-ko were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (1-19), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1, 2, 6, 11, and 18 exhibited obvious activity against α-glucosidase with IC50 values of 5.2-9.0 µM, 20-35 times stronger than that of acarbose (IC50, 180.0 µM); meanwhile, 6, 10-12, and 19 were PTP1B/TCPTP-selective inhibitors with IC50 values of 56.4-80.4 µM, 2-4 times stronger than that of suramin sodium (IC50, 200.5 µM). Enzyme kinetics study indicated that compounds 1, 2, 6, and 11 were α-glucosidase and PTP1B mixed-type inhibitors with Ki values of 13.0, 11.7, 2.9, and 5.3 µM and 142.3, 88.9, 39.2, and 40.8 µM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.