The connections of sialic acids and diabetes mellitus: therapeutic or diagnostic value?

Modulation of sialic acids is one of the important pathological consequences of both type 1 and type 2 diabetes mellitus with or without the micro- and macrovascular complications. However, the mechanistic, therapeutic and/or diagnostic implications of these observations are uncoordinated and possibly conflicting. This review critically analyses the scientific investigations connecting sialic acids with diabetes mellitus. Generally, variations in the levels and patterns of sialylation, fucosylation and galactosylation were predominant across various tissues and body systems of diabetic patients, but the immune system seemed to be most affected. These might be explored as a basis for differential diagnosis of various diabetic complications. Sialic acids are predominantly elevated in nearly all forms of diabetic conditions, particularly nephropathy and retinopathy, which suggests some diagnostic value but the mechanistic details were not unequivocal from the available data. The plausible mechanistic explanations for the elevated sialic acids are increased desialylation by sialidases, stimulation of hexosamine pathway and synthesis of acute phase proteins as well as oxidative stress. Additionally, sialic acids are also profoundly associated with glucose transport and insulin resistance in human-based studies while animal-based studies revealed that the increased desialylation of insulin receptors by sialidases, especially NEU1, might be the causal link. Interestingly, inhibition of the diabetes-associated NEU1 desialylation was beneficial in diabetes management and might be considered as a therapeutic target. It is hoped that the article will provide an informed basis for future research activities on the exploitation of sialic acids and glycobiology for therapeutic and/or diagnostic purposes against diabetes mellitus.

Evaluating Khaya senegalensis for Dipeptidyl Peptidase-IV Inhibition Using in Vitro Analysis and Molecular Dynamic Simulation of Identified Bioactive Compounds.

The dipeptidyl peptidase-IV (DPP-IV) inhibitory activity of Khaya senegalensis extracts was evaluated. The DPP-IV from a rat kidney was purified to a purification fold of 2.3. Among extracts from K. senegalensis, the hexane extract had the best DPP-IV inhibitory activity, with IC50 value of 1.56±0.61 µg/mL and was fractionated to eleven fractions (A-K). Fraction I had the best DPP-IV inhibition via uncompetitive pattern. GC-MS analysis of fraction I showed that the major bioactive compounds were 3-amino-3-hydroxyimino-N-phenylpropanamide (1) and 11-(2-cyclopenten-1-yl)undecanoic acid (2), with good binding affinities toward DPP-IV, based on molecular docking,. They were then subjected to molecular dynamic simulation using WEBGRO and utilizing a GROMACS system for 100 ns. The 3-amino-3-hydroxyimino-N-phenylpropanamide-DPP-IV complex was more stable and compact than the other complex. K. senegalensis contains compounds like 1 that might be used for the design of new DPP-IV inhibitors.

Microbial Population and Physicochemical Properties of Miang Fermented in Bamboo Tubes by the Luar Ethnic Group in Lao PDR.

Miang is a traditional fermented food made from Assam tea leaves and consumed as a snack. This study investigated the underground Miang fermentation process practiced by the Luar ethnic group in Laos, specifically examining the nutritional composition and microbial dynamics. Lactic acid bacteria and yeast were dominant in the fermentation process, reaching 8.43 and 8.50 log CFU/g after one week before gradually declining, while the coliform bacterial count was at 5.31 log CFU/g in the initial week but became undetectable in the later stages of fermentation. Next-generation sequencing identified Firmicutes (75.02%) and Proteobacteria (23.51%) as the primary phyla. Bacterial genera included Lactobacillus (73.36%) and Acetobacter (21.06%), with fungi mainly represented by Pichia (85.52%) and Candida (13.45%). Fundamental microbes such as Lactobacillus and Acetobacter were predominantly present, alongside Pichia and Candida, in the fungal communities. Microbial activities played a crucial role in generating essential enzymes for Miang's transformation. The nutritional transformation appears to be complete at 5 weeks of fermentation. The moisture content in the final products was approximately 74% and correlated with a change in nitrogen-free extract (NFE) and crude fiber. The fat content showed a slight increase from 1.3% to 2.52%, but protein content slightly declined from 17.21% to 16.05%, whereas ash content did not change significantly. Key polysaccharide-degrading enzymes, particularly pectinase and ß-mannanase, were revealed and peaked at 48.32 and 25.32 U/g Miang, respectively. The total polyphenols increased from 103.54 mg/g dry Miang to 144.19-155.52 mg/g during fermentation. The lowered IC50 value indicated an increase in antioxidant activity. A fermentation period of at least 3 weeks proved to be optimal for enhancing antioxidant properties and bioactive compounds, and mitigating the risk of coliform bacteria.

Antibacterial activities of Miang extracts against selected pathogens and the potential of the tannin-free extracts in the growth inhibition of Streptococcus mutans.

Bacterial pathogens have remained a major public health concern for several decades. This study investigated the antibacterial activities of Miang extracts (at non-neutral and neutral pH) against Bacillus cereus TISTR 747, Escherichia coli ATCC 22595, Salmonella enterica serovar Typhimurium TISTR 292 and Streptococcus mutans DMST 18777. The potential of Polyvinylpolypyrrolidone (PVPP)-precipitated tannin-free Miang extracts in growth-inhibition of the cariogenic Streptococcus mutans DMST 18777 and its biofilms was also evaluated. The tannin-rich fermented extracts had the best bacterial growth inhibition against S. mutans DMST 18777 with an MIC of 0.29 and 0.72 mg/mL for nonfilamentous fungi (NFP) Miang and filamentous-fungi-processed (FFP) Miang respectively. This observed anti-streptococcal activity still remained after PVPP-mediated precipitation of bioactive tannins especially, in NFP and FFP Miang. Characterization of the PVPP-treated extracts using High performance liquid chromatography quadrupole-time of flight-mass spectrometry (HPLC-QToF-MS) analysis, also offered an insight into probable compound classes responsible for the activities. In addition, Crystal violet-staining also showed better IC50 values for NFP Miang (4.30 ± 0.66 mg/mL) and FFP Miang (12.73 ± 0.11 mg/mL) against S. mutans DMST 18777 biofilms in vitro. Homology modeling and molecular docking analysis using HPLC-MS identified ligands in tannin-free Miang supernatants, was performed against modelled S. mutans DMST 18777 sortase A enzyme. The in silico analysis suggested that the inhibition by NFP and FFP Miang might be attributed to the presence of ellagic acid, flavonoid aglycones, and glycosides. Thus, these Miang extracts could be optimized and explored as natural active pharmaceutical ingredients (NAPIs) for applications in oral hygienic products.

Tannin-Tolerant Saccharomyces cerevisiae Isolated from Traditional Fermented Tea Leaf (Miang) and Application in Fruit Wine Fermentation Using Longan Juice Mixed with Seed Extract as Substrate.

This study focused on isolating tannin-tolerant yeasts from Miang, a fermented tea leaf product collected from northern Laos PDR, and investigating related food applications. From 43 Miang samples, six yeast isolates capable of ethanol production were obtained, with five isolates showing growth on YPD agar containing 4% (w/v) tannic acid. Molecular identification revealed three isolates as Saccharomyces cerevisiae (B5-1, B5-2, and C6-3), along with Candida tropicalis and Kazachstania humilis. Due to safety considerations, only Saccharomyces spp. were selected for further tannic acid tolerance study to advance food applications. Tannic acid at 1% (w/v) significantly influenced ethanol fermentation in all S. cerevisiae isolates. Notably, B5-2 and C6-3 showed high ethanol fermentation efficiency (2.5% w/v), while others were strongly inhibited. The application of tannin-tolerant yeasts in longan fruit wine (LFW) fermentation with longan seed extract (LSE) supplementation as a source of tannin revealed that C6-3 had the best efficacy for LFW fermentation. C6-3 showed promising efficacy, particularly with LSE supplementation, enhancing phenolic compounds, antioxidant activity, and inhibiting α-glucosidase activity, indicating potential antidiabetic properties. These findings underscore the potential of tannin-tolerant S. cerevisiae C6-3 for fermenting beverages from tannin-rich substrates like LSE, with implications for functional foods and nutraceuticals promoting health benefits.

Comparison of Phenolic Contents and Scavenging Activities of Miang Extracts Derived from Filamentous and Non-Filamentous Fungi-Based Fermentation Processes.

The study investigated the impact of the fermentation process on the phenolic contents and antioxidant and anti-inflammatory activities in extracts of Miang, an ethnic fermented tea product of northern Thailand. The acetone (80%) extraction of Miang samples fermented by a non-filamentous fungi-based process (NFP) and filamentous fungi-based process (FFP) had elevated levels of total polyphenols, total tannins, and condensed tannins compared to young and mature tea leaves. The antioxidant studies also showed better the half-maximal inhibitory concentration (IC50) values for fermented leaves in both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity assays as well as improved ferric reducing antioxidant power (FRAP) compared to young and mature tea leaves. Extracts of NFP and FFP samples at concentrations of 50 and 100 ppm showed better protective effects against hydrogen peroxide (H2O2)-induced intracellular reactive oxygen species (ROS) production in HT-29 colorectal cells without exerting cytotoxicity. Additionally, lipopolysaccharide (LPS)-induced production of nitric oxide (a proinflammatory mediator as well as a reactive nitrogen species) was also inhibited by these fermented Miang extracts with an IC50 values of 17.15 µg/mL (NFP), 20.17 µg/mL (FFP), 33.96 µg/mL (young tea leaves), and 31.33 µg/mL (mature tea leaves). Therefore, both NFP-Miang and FFP-Miang showed the potential to be targeted as natural bioactive functional ingredients with preventive properties against free radical and inflammatory-mediated diseases.