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Journal of Enzyme Inhibition and... Dec 2024Inhibition of α-glucosidase and -amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat...
Inhibition of α-glucosidase and -amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-] quinoxalines-carrying thiazole hybrids were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds , , , and were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against -glucosidase and -amylase enzymes . The four hybrids , , , and represented moderate to potent activity with IC values 0.982 ± 0.04, to 10.19 ± 0.21 for -glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 μM for -amylase inhibition when compared to the standard medication acarbose with IC=0.316 ± 0.02 μM for -glucosidase inhibition and 31.56 ± 1.33 μM for -amylase inhibition. Docking studies as well as ADMT were done.
Topics: Quinoxalines; alpha-Amylases; alpha-Glucosidases; Molecular Docking Simulation; Hypoglycemic Agents; Animals; Mice; Structure-Activity Relationship; Glycoside Hydrolase Inhibitors; Molecular Structure; Thiazoles; Dose-Response Relationship, Drug; Diabetes Mellitus, Experimental; Streptozocin; Halogenation; Male; Enzyme Inhibitors
PubMed: 38913598
DOI: 10.1080/14756366.2024.2367128 -
Gut Microbes 2024Resistant starch (RS) consumption can have beneficial effects on metabolic health, but the response, in terms of effects on the gut microbiota and host physiology,...
Resistant starch (RS) consumption can have beneficial effects on metabolic health, but the response, in terms of effects on the gut microbiota and host physiology, varies between individuals. Factors predicting the response to RS are not yet established and would be useful for developing precision nutrition approaches that maximize the benefits of dietary fiber intake. We sought to identify predictors of gut microbiota response to RS supplementation. We enrolled 76 healthy adults into a 7-week crossover study with 59 individuals completing the study. Participants consumed RS type 2 (RS2), RS type 4 (RS4), and digestible starch, for 10 d each with 5-d washout periods in between. We collected fecal and saliva samples and food records during each treatment period. We performed 16S rRNA gene sequencing and measured fecal short-chain fatty acids (SCFAs), salivary amylase () gene copy number, and salivary amylase activity (SAA). Dietary fiber intake was predictive of the relative abundance of several amplicon sequence variants (ASVs) at the end of both RS treatments. -related metrics were not predictive of response to RS. SAA was only predictive of the relative abundance of one ASV after digestible starch supplementation. Interestingly, SCFA concentrations increased the most during digestible starch supplementation. Treatment order (the order of consumption of RS2 and RS4), alpha diversity, and a subset of ASVs were predictive of SCFA changes after RS supplementation. Based on our findings, dietary fiber intake and gut microbiome composition would be informative if assessed prior to recommending RS supplementation because these data can be used to predict changes in specific ASVs and fecal SCFA concentrations. These findings lay a foundation to support the premise that using a precision nutrition approach to optimize the benefits of dietary fibers such as RS could be an effective strategy to compensate for the low consumption of dietary fiber nationwide.
Topics: Humans; Dietary Fiber; Gastrointestinal Microbiome; Male; Female; Feces; Adult; Fatty Acids, Volatile; Starch; Cross-Over Studies; Saliva; Dietary Supplements; Bacteria; RNA, Ribosomal, 16S; Young Adult; Middle Aged; Resistant Starch
PubMed: 38913541
DOI: 10.1080/19490976.2024.2367301 -
The American Journal of Gastroenterology Jun 2024Aggressive hydration using lactated Ringer's solution (LRS) prevents post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Concerns of this...
OBJECTIVES
Aggressive hydration using lactated Ringer's solution (LRS) prevents post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Concerns of this strategy are large volume and lengthy hydration. Our study aimed to evaluate the efficacy of tailored aggressive hydration (TAH) for PEP prevention.
METHODS
In this prospective, multicenter, double-blinded, randomized trial conducted across three tertiary Korean hospitals, patients who underwent ERCP for the first-time were randomly assigned (1:1) to tailored standard hydration (TSH) and TAH groups. The TSH group received 1.5 mL/kg/h LRS during and after ERCP, whereas the TAH group was administered a 20 mL/kg bolus post-ERCP and 3 mL/kg/h during and after the procedure. Both groups were assessed for elevated serum amylase levels and pain 4-6 h after ERCP. If both were absent, hydration was discontinued. If either was present, hydration was continued at the original rate until 8 h. The primary endpoint was PEP development and was analyzed on an intention-to-treat analysis.
RESULTS
A total of 344 patients were randomly assigned to treatment groups (171 to the TSH group and 172 to the TAH group). PEP was observed in 9.4% (16/171) in the TSH group and 3.5% (6/172) in the TAH group (relative risk 0.37, 95% confidence interval 0.15-0.93, p = 0.03). No difference was identified between the two groups in terms of PEP severity (p = 0.80) and complications related to volume overload (p = 0.32).
CONCLUSIONS
TAH according to the presence of abdominal pain or elevated serum amylase levels at 4-6 h after ERCP is safe and prevents PEP development.
PubMed: 38912692
DOI: 10.14309/ajg.0000000000002903 -
Iranian Journal of Basic Medical... 2024Acute pancreatitis (AP) is an abrupt inflammatory condition characterized by a storm of inflammatory cytokines leading to high morbidity and mortality. The current study...
OBJECTIVES
Acute pancreatitis (AP) is an abrupt inflammatory condition characterized by a storm of inflammatory cytokines leading to high morbidity and mortality. The current study aimed to examine the efficacy of extract EGb 761 (GBE) in the treatment of L-arginine-induced AP and its associated lung injury.
MATERIALS AND METHODS
Forty rats were randomly assigned into four groups. The normal group received only saline intraperitoneally while the other groups received two intraperitoneal L-arginine injections (250 mg/100 g b.wt) separated by a 1-hour interval to provoke AP. GBE (200 and 400 mg/kg/day, PO) was administered for 2 weeks post-induction of pancreatitis. Sera and pancreatic tissues were isolated.
RESULTS
The outcome of the present study revealed that GBE ameliorated the elevated levels of serum amylase, lipase, and pancreatic inflammatory mediators viz., tumor necrosis factor-alpha (TNF-α), mitogen-activated protein kinase P38 (MAPK-P38), c-Jun N-terminal kinase 1 (JNK1), and nuclear factor-kappa B (NF-κB). Moreover, GBE restored the pancreatic gene expression of Toll-like receptor 4 (TLR4) and prostatic acid phosphatase-2 (PAP-2). Pancreatic and lung histopathological examinations confirmed the aforementioned parameters.
CONCLUSION
GBE interfered with the mechanistic pathway of L-arginine-induced acute pancreatic and its associated lung injury. Due to its anti-inflammatory properties, GBE can be used as a novel therapeutic candidate for the treatment of AP through down-regulating TLR-4/MAPK-p38/JNK and MAPK- p38/NF-κB signaling cascades.
PubMed: 38911245
DOI: 10.22038/IJBMS.2024.76162.16480 -
Plant Direct Jun 2024The coordination of assimilation pathways for all the elements that make up cellular components is a vital task for every organism. Integrating the assimilation and use...
The coordination of assimilation pathways for all the elements that make up cellular components is a vital task for every organism. Integrating the assimilation and use of carbon (C) and nitrogen (N) is of particular importance because of the high cellular abundance of these elements. Starch is one of the most important storage polymers of photosynthetic organisms, and a complex regulatory network ensures that biosynthesis and degradation of starch are coordinated with photosynthetic activity and growth. Here, we analyzed three starch metabolism enzymes of that we captured by a cyclic guanosine monophosphate (cGMP) affinity chromatography approach, namely, soluble starch synthase STA3, starch-branching enzyme SBE1, and α-amylase AMA2. While none of the recombinant enzymes was directly affected by the presence of cGMP or other nucleotides, suggesting an indirect binding to cGMP, AMA2 activity was stimulated in the presence of L-glutamine (Gln). This activating effect required the enzyme's N-terminal aspartate kinase-chorismate mutase-tyrA domain. Gln is the first N assimilation product and not only a central compound for the biosynthesis of N-containing molecules but also a recognized signaling molecule for the N status. Our observation suggests that AMA2 might be a means to coordinate N and C metabolism at the enzymatic level, increasing the liberation of C skeletons from starch when high Gln levels signal an abundance of assimilated N.
PubMed: 38911017
DOI: 10.1002/pld3.609 -
Frontiers in Pharmacology 2024Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality....
BACKGROUND
Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality. Oxidative stress and activation of inflammatory pathways represent major players in AP pathogenesis. Current management of AP relies on attenuating injuries to the pancreas and putting the inflammatory process under control. In this study, we investigated the role of sitagliptin in modulating L-arginine-induced AP in rats.
METHODS
Swiss rats were subdivided into a healthy control group, AP group (a single dose of L-arginine 250 mg/100 g, intraperitoneal), and sitagliptin + L-arginine-treated group (10 mg sitagliptin/kg body weight/day, orally). Sitagliptin treatment started 1 hour after L-arginine injection and continued for 3days. Biochemical and histopathological investigations were performed on serum and tissue samples collected from test animals.
RESULTS
L-arginine increased pancreatic meyloperoxidase and serum amylase- and lipase activities and serum levels of TNF-α, LT-α, IFN-γ, IL-1α/β, IL-6, IL-10, IL-12, and IL-15. AP animals showed elevated MDA and NO and decreased GSH and serum calcium levels. Histopathological changes were observed by H&E staining. Sitagliptin treatment significantly ameliorated these biochemical and histological changes diminishing the signs of AP.
CONCLUSION
Sitagliptin treatment was effective in ameliorating L-arginine-induced AP which can be regarded to its anti-inflammatory and antioxidant effect.
PubMed: 38910880
DOI: 10.3389/fphar.2024.1389670 -
Future Medicinal Chemistry 2024The objective of the present investigation was to design and synthesize new heterocyclic hybrids comprising benzothiazole and indenopyrazolone pharmacophoric units in a...
The objective of the present investigation was to design and synthesize new heterocyclic hybrids comprising benzothiazole and indenopyrazolone pharmacophoric units in a single molecular framework targeting α-amylase and α-glucosidase enzymatic inhibition. 20 new benzothiazole-appended indenopyrazoles, , were synthesized in good yields under environment-friendly conditions via cycloaddition reaction, and assessed for antidiabetic activity against α-amylase and α-glucosidase, using acarbose as the standard reference. Among all the hydroxypyrazolones, and showed the best inhibition against α-amylase and α-glucosidase, which finds support from molecular docking and dynamic studies. Compounds and have been identified as promising antidiabetic agents against α-amylase and α-glucosidase and could be considered valuable leads for further optimization of antidiabetic agents.
Topics: alpha-Glucosidases; Benzothiazoles; alpha-Amylases; Molecular Docking Simulation; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Humans; Pyrazoles; Structure-Activity Relationship; Molecular Structure; Enzyme Inhibitors
PubMed: 38910576
DOI: 10.4155/fmc-2023-0384 -
Zeitschrift Fur Naturforschung. C,... Jun 2024Benzene sulfonamides are an important biological substituent for several activities. In this study, hybridization of benzene sulfonamide with piperazine derivatives were...
Benzene sulfonamides are an important biological substituent for several activities. In this study, hybridization of benzene sulfonamide with piperazine derivatives were investigated for their antioxidant capacity and enzyme inhibitory potencies. Six molecules were synthesized and characterized. DPPH, ABTS, FRAP, CUPRAC, chelating and phosphomolybdemum assays were applied to evaluate antioxidant capacities. Results show that compounds have high antioxidant capacity and compound has the best antioxidant activity among them. Compound has higher antioxidant activity than references for FRAP (IC: 0.08 mM), CUPRAC (IC: 0.21 mM) and phosphomolybdenum (IC: 0.22 mM) assays. Besides this, compound has moderate DPPH and ABTS antioxidant capacity. Furthermore, enzyme inhibition activities of these molecules were investigated against AChE, BChE, tyrosinase, -amylase and -glucosidase enzymes. It was revealed that all compounds have good enzyme inhibitory potential except for -amylase enzyme. The best inhibitory activities were observed for AChE with compound the same value (IC: 1.003 mM), for BChE with compounds and the same value (IC: 1.008 mM), for tyrosinase compound (IC: 1.19 mM), and for -glucosidase with compound (IC: 1.000 mM). Docking studies have been conducted with these molecules, and the results correlate well with the inhibitory assays.
PubMed: 38909275
DOI: 10.1515/znc-2024-0062 -
Journal of Dairy Science Jun 2024The production of whey protein concentrates (WPCs) from camel milk whey represents an effective approach to valorize this processing by-product. These concentrates...
The production of whey protein concentrates (WPCs) from camel milk whey represents an effective approach to valorize this processing by-product. These concentrates harbor active ingredients with significant bioactive properties. Camel WPCs were spray-dried (SD) at inlet temperature of 170, 185 and 200°C, or Ultrasonicated (US) for 5, 10 and 15 min, then freeze-dried to obtain fine powder. The impact of both treatments on protein degradation was studied by sodium dodecyl sulfate-PAGE and reverse-phase ultraperformance liquid chromatography (RP-UPLC) techniques. Significantly enhanced protein degradation was observed after US treatment when compared with SD. Both SD and US treatments slightly enhanced the WPCs samples' antioxidant activities. The US exposure for 15 min exhibited highest 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity (12.12 mmol TE/g). Moreover, US treatment for 10 min exhibited the highest in vitro anti-diabetic properties (α-amylase and α-glucosidase inhibition), and dipeptidyl-peptidase-IV inhibitory activity among all samples. In addition, the ultrasonication for 10 min and SD at 170°C showed the lowest IC values for in vitro anti-hypercholesterolemic activities in terms of pancreatic lipase and cholesteryl esterase inhibition. Conclusively, these green techniques can be adapted in the preservation and processing of camel milk whey into active ingredients with high bioactive properties.
PubMed: 38908705
DOI: 10.3168/jds.2024-24900 -
Journal of Proteome Research Jun 2024To investigate the mechanisms underlying the differences in the freezability of boar semen, Yorkshire boars with freezing-tolerant semen (YT, = 3), Yorkshire boars with...
To investigate the mechanisms underlying the differences in the freezability of boar semen, Yorkshire boars with freezing-tolerant semen (YT, = 3), Yorkshire boars with freezing-sensitive semen (YS, = 3), Landrace boars with freezing-tolerant semen (LT, = 3), and Landrace boars with freezing-sensitive semen (LS, = 3) were selected for this study. Their sperm was subjected to protein extraction, followed by data-independent acquisition proteomics and functional bioinformatics analysis. A total of 3042 proteins were identified, of which 2810 were quantified. Some key KEGG pathways were enriched, such as starch and sucrose metabolism, carbohydrate digestion and absorption, mineral absorption, the HIF-1 signaling pathway, and the necroptosis pathways. Through PRM verification, we found that several proteins, such as α-amylase and epididymal sperm-binding protein 1, can be used as molecular markers of the freezing resistance of boar semen. Furthermore, we found that the addition of α-amylase to cryoprotective extender could significantly improve the post-thaw motility and quality of boar semen. In summary, this study revealed some molecular markers and potential molecular pathways contributing to the high or low freezability of boar sperm, identifying α-amylase as a key protein. This study is valuable for optimizing boar semen cryopreservation technology.
PubMed: 38906844
DOI: 10.1021/acs.jproteome.4c00367