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Hemi-pyocyanin (HPC) is a heterocyclic nitrogenous compound with some reported potential medical effects. The current report aimed to investigate the potential use of organic industrial waste for the production of HPC via microbial fermentation. The novel antidiabetic activity of HPC was also accessed and reported in this work. A peanut oil processing by-product (groundnut cake) was screened as the best substrate for Pseudomonas aeruginosa TUN03 conversion to obtain high-yield HPC. This compound was further produced in a 14 L bioreactor system on a large scale (6 L per pilot) and reached higher productivity (35.1 μg/mL) in a shorter time course of cultivation (8 h) compared to fermentation on a small scale in flasks (19.5 μg/mL; 3 days of fermentation). On assessing its activity, HPC demonstrated potent inhibition against α-glucosidase, an antidiabetic enzyme, with a low IC50 value (0.572 mg/mL) and a maximum inhibition rate of 100%. In an in silico study, HPC was found to inhibit α-glucosidase with a good binding energy score (−9.0 kcal/mol) via interaction with amino acids Lys156, Leu313, and Arg315 at the active site, and three bonds (1 H-acceptor and 2 pi-H) were generated. The data from five Lipkin's rules and ADMET-based pharmacokinetics and pharmacology revealed that HPC possesses drug-like properties and good ADMET properties within the required allotted limitations. The data obtained in the current work highlighted the potential application of groundnut cakes for the eco-friendly and scaled-up production of HPC, a new anti-α-glucosidase agent that should be further investigated for type 2 diabetes management. [ABSTRACT FROM AUTHOR]

α-Amylase inhibitors (aAIs) have been applied for the efficient management of type 2 diabetes. The aim of this study was to search for potential aAIs produced by microbial fermentation. Among various bacterial strains, Pseudomonas aeruginosa TUN03 was found to be a potential aAI-producing strain, and shrimp heads powder (SHP) was screened as the most suitable C/N source for fermentation. P. aeruginosa TUN03 exhibited the highest aAIs productivity (3100 U/mL) in the medium containing 1.5% SHP with an initial pH of 7–7.5, and fermentation was performed at 27.5 °C for two days. Further, aAI compounds were investigated for scaled-up production in a 14 L-bioreactor system. The results revealed a high yield (4200 U/mL) in a much shorter fermentation time (12 h) compared to fermentation in flasks. Bioactivity-guided purification resulted in the isolation of one major target compound, identified as hemi-pyocyanin (HPC) via gas chromatography-mass spectrometry and nuclear magnetic resonance. Its purity was analyzed by high-performance liquid chromatography. HPC demonstrated potent α-amylase inhibitory activity comparable to that of acarbose, a commercial antidiabetic drug. Notably, HPC was determined as a new aAI. The docking study indicated that HPC inhibits α-amylase by binding to amino acid Arg421 at the biding site on enzyme α-amylase with good binding energy (−9.3 kcal/mol) and creating two linkages of H-acceptors. [ABSTRACT FROM AUTHOR]

Euonymus laxiflorus Champ. (ELC) has been reported to possess potential antidiabetic activity. The aim of this study is to isolate and identify the active compounds in ELC extract. Application of effective techniques including Diaoin, octadecylsilane opened columns, dialysis, and preparative high-performance liquid chromatography (HPLC) coupled with a biologically guided assay resulted in isolation of 11 novel active compounds. Five compounds were identified as new α-amylase inhibitors (αAIs), viz. walterolactone A/B β- d-pyranoglucoside ( 1), schweinfurthinol 9- O-β- d-pyranoglucoside ( 10), 1- O-(3-methyl)-butenoyl-myo-inositol ( 11), leonuriside ( 13), and (3,5-dimethoxy-4-hydroxyphenol) -1- O-β- d-(6′- O-galloyl)-glucopyranoside ( 21). Among these inhibitors, three compounds ( 1, 10, 11) were characterized as new. Another six known compounds ( 2, 9, 16, 17, 18, 19) were determined as phenolic. Notably, six compounds ( 1, 2, 9, 13, 16, 17) demonstrated significant activity, comparable to or higher than that of acarbose, a commercial antidiabetic drug, based on t test ranking. The relationship between the chemical structures and bioactivity of the inhibitors is also reported. [ABSTRACT FROM AUTHOR]

Anti-α-glucosidase (AAG) compounds have received great attention due to their potential use in treating diabetes. In this study, Bacillus licheniformis TKU004, an isolated bacterial strain from Taiwanese soil, produced AAG activity in the culture supernatant when squid pens were used as the sole carbon/nitrogen (C/N) source. The protein TKU004P, which was isolated from B. licheniformis TKU004, showed stronger AAG activity than acarbose, a commercial anti-diabetic drug (IC50 = 0.1 mg/mL and 2.02 mg/mL, respectively). The molecular weight of TKU004P, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was 29 kDa. High-performance liquid chromatography (HPLC) analysis showed that TKU004P may be a protease that demonstrates AAG activity by degrading yeast α-glucosidase. Among the four chitinous sources of C/N, TKU004P produced the highest AAG activity in the culture supernatant when shrimp head powder was used as the sole source (470.66 U/mL). For comparison, 16 proteases, were investigated for AAG activity but TKU004P produced the highest levels. Overall, the findings suggest that TKU004P could have applications in the biochemical and medicinal fields thanks to its ability to control the activity of α-glucosidase. [ABSTRACT FROM AUTHOR]

α-Glucosidase inhibitors (aGIs) have been used as an effective therapy for type-2 diabetes, which remains a global health issue. The aim of this study was to achieve bioactivity-guided isolation, identification and evaluation of hypoglycemic compounds from Euonymus laxiflorus Champ. trunk bark (ELCTB). Eleven active compounds were isolated and identified as walterolactone A/B β-d-pyranoglucoside (1), 1-β-d-glucopyranosyloxy-3,5-dimethoxy-4-hydroxybenzene (9), (−)-gallocatechin (10), schweinfurthinol 9-O-β-d-pyranoglucoside (11), 1-O-(3-methyl)-butenoyl-myo-inositol (12), leonuriside (14), (+)-catechin (19), methyl galloate (20), (−)-catechin (23), and condensed tannins (5 and 18). Of these 11, novel 4 compounds (1, 11, 12, and 14) were found as new α-glucosidase inhibitors. Notably, in vitro results indicated that compounds 1, 5, 10–12, 18, and 19 showed potent activity (IC50 = 0.076−31 µg/mL), and their activities were at a higher level than that of acarbose, a commercial inhibitor (IC50 = 1345 µg/mL). In animal tests, the major inhibitor, condensed tannin (18), demonstrated significant reduction of plasma glucose in mice with no symptoms of diarrhea at the dose of 100 mg/kg bw. The results suggest that Euonymus laxiflorus Champ. is a rich source of bioactive compounds for development as health food or drugs with potent hypoglycemic effect. The results of this study also enriched the current novel biological activities of constituents from Euonymus laxiflorus species. [ABSTRACT FROM AUTHOR]