A contribution to lipid digestion of Odobenidae family: Computational analysis of gastric and pancreatic lipases from walrus (Odobenus rosmarus divergens).

Triacylglycerols (TAGs) are a primary energy source for marine mammals during lipid digestion. Walruses (Odobenus rosmarus divergens) consume prey with a high content of long-chain polyunsaturated fatty acids; however, their digestive physiology and lipid digestion remain poorly studied. The present study aims to model and characterize the gastric (PWGL) and pancreatic (PWPL) lipases of Pacific walruses using an in-silico approach. The confident 3D models of PWGL and PWPL were obtained via homology modeling and protein threading and displayed the structural features of lipases. Molecular docking analysis demonstrated substrate selectivity for long-chain TAG (Trieicosapentaenoin; TC20:5n-3) in PWGL and short-chain TAG (Trioctanoin; TC8:0) in PWPL. Molecular dynamics simulations demonstrate that PWGL bound to tridocosahexaenoin (TC22:6n-3), the protein is considerably stable at all three salinity conditions, but fluctuations are observed in the regions associated with catalytic sites and the lid, indicating the potential hydrolysis of the substrate. This is the first study to report on the digestion of TAGs in walruses, including modeling and lipases characterization and proposing a digestive tract for pinnipeds.

Antioxidant capacity and inhibition of metabolic syndrome-associated enzymes by Cryptocarya alba fruits.

The fruits of the native tree Cryptocarya alba Mol. (Lauraceae), known as "peumo" were consumed by the Mapuche Amerindians in Chile both raw and after boiling. The aim of this work was to compare the content of phenolic, procyanidins, antioxidant capacity and inhibition of enzymes related with metabolic syndrome (α-glucosidase, α-amylase and pancreatic lipase) from the phenolic enriched extracts (PEEs) of peumo fruits. Fruits were collected during two years in three different places in central Chile and were investigated raw, boiled, and after separation into cotyledons and peel. The water resulting from the fruit decoction was also analyzed. The composition of the PEE was assessed by HPLC-DAD-MS/MS and the main compounds were quantified by HPLC. The strong inhibitory effect on α-glucosidase, with IC50 values below 1 µg/mL for several samples, was related, at least in part, to the content of 3-caffeoylquinic acid, 5-caffeoylquinic acid and (-)-epicatechin. The effect of the PEE on pancreatic lipase is of interest and can be partially explained by the (-)-epicatechin content. PCA analyses showed a clear separation of the samples according to the fruit parts and processing. However, no differences by geographic origin were observed. The activity of peumo PEEs on enzymes related to metabolic syndrome and its antioxidant capacity support further studies on the health promoting properties of this native Chilean food plant.

Metabolomic Characterization of Phoradendron brachystachyum Mistletoe and In-Silico and In-Vitro Investigation of Its Therapeutic Potential in Metabolic Disorders.

Plants of the Phoradendron genus have been traditionally used for their lipid- and glucose-lowering effects. However, the compounds responsible for these effects and the overall chemical profile of these plants have not been thoroughly investigated. We aimed to characterize the metabolome of leaves, stems, and aerial parts of the Phoradendron brachystachyum plant. We used mass spectrometry and colorimetric screening techniques (with various solvents) to identify and characterize the metabolites present. We also evaluated the antioxidant (FRAP, ORAC, TEAC, and DPPH assays) and inhibitory effects on pancreatic lipase and α-glucosidase enzymes of hydrophilic extracts. Furthermore, we compared the molecular fingerprints between the identified metabolites and FDA-approved drugs to gain insights into the metabolites that might be responsible for the observed effects on enzymes. Our findings revealed the presence of 59 putative metabolites, primarily flavonoids. However, we also hint at the presence of peptide and carbohydrate derivatives. The leaf extracts demonstrated the most promising metrics across all assays, exhibiting strong antioxidant and enzyme inhibitory effects as well as high levels of phenolic compounds, flavonoids, and tannins. Fingerprint analysis suggested potential peptide and carbohydrate metabolites as pancreatic lipase and α-glucosidase inhibitors. Overall, our study provides evidence on specific metabolites in Phoradendron brachystachyum that could be responsible for the therapeutic effects noted in obese and type 2 diabetes subjects.

Inhibitory Potential of Synthetic Amino Acid Derivatives against Digestive Enzymes as Promising Hypoglycemic and Anti-Obesity Agents.

Over the last decades, the increased incidence of metabolic disorders, such as type two diabetes and obesity, has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes were assessed using in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated using kinetic parameters and Lineweaver-Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 167-1023 µM) via competitive or mixed mechanisms. The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 162-519 µM), which acted as competitive or mixed inhibitors. Finally, PPC84, PPC89, and PPC101 also showed potent inhibitory effects on α-glucosidase (IC50 of 51-353 µM) as competitive inhibitors. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

Hypoglycemic effect of Coffea arabica leaf extracts and major bioactive constituents.

The present study focused on investigating the antioxidant, antiglycation activity, digestive enzymes inhibition, bioaccessibility and hypoglycemic effect of C. arabica leaves extracts. The extracts deactivated the O2•-, ROO•, H2O2, HOCl reactive oxygen species. Coffee leaves showed strong inhibition of α-glucosidase (IC50 = 40.30 µg mL-1) greater than the isolated metabolites and acarbose. There was also inhibition of pancreatic lipase (IC50 = 56.43 µg mL-1) in addition to a hypoglycemic effect in zebrafish similar to acarbose and metformin. With the exception of rutin, all biocompounds were detected at all stages of in vitro digestion. Finally, these results suggest that C. arabica leaf extracts possess antidiabetic and anti-obesity properties that can be attributed to the main metabolites and the synergistic action between them.Communicated by Ramaswamy H. Sarma.

Bioaccessibility of Phenolic Compounds from Mistletoe Infusions and Effect of In Vitro Digestion on Its Antioxidant and Pancreatic Lipase Inhibitory Activity.

Phoradendron brachystachyum is an American mistletoe distributed in México and used ethnobotanically in infusions to treat hypertriglyceridemia and lower cholesterol levels. This study aimed to evaluate the bioaccessibility of the phenolic acids from mistletoe infusions and the effect of simulated digestion on its antioxidant and lipase inhibitory properties. The in vitro digestion process decreased the antioxidant capacity activity by the TEAC and ORAC assays in infusions from leaves, stems, and whole plant samples. Moreover, the individual phenolic content of mistletoe infusions was also affected by the in vitro digestion process; the most abundant individual phenolic constituents at the end of the digestion process were ferulic and quinic acids. These compounds showed low bioaccessibility values ranging from 7.48% to 22.60%. In addition, the in vitro digestion diminished the pancreatic lipase inhibition percentage of leaves and whole plant infusions but increased it in the stem samples. This research showed that given the phenolic content and pancreatic lipase inhibitory activity of mistletoe infusions, it could be used as a potential source for the development of functional foods and nutraceuticals; nonetheless, its phenolic content is affected by gastrointestinal digestion; thus, encapsulation strategies are encouraged to protect these metabolites from the gastrointestinal environment while preserving their antioxidant and hypolipidemic potentials.

In Vitro and In Silico Study of the α-Glucosidase and Lipase Inhibitory Activities of Chemical Constituents from Piper cumanense (Piperaceae) and Synthetic Analogs.

Digestive enzymes are currently considered important therapeutic targets for the treatment of obesity and some associated metabolic diseases, such as type 2 diabetes. Piper cumanense is a species characterized by the presence of bioactive constituents, particularly prenylated benzoic acid derivatives. In this study, the inhibitory potential of chemical constituents from P. cumanense and some synthesized compounds was determined on digestive enzymes (pancreatic lipase (PL) and α-glucosidase (AG)). The methodology included isolating and identifying secondary metabolites from P. cumanense, synthesizing some analogs, and a molecular docking study. The chemical study allowed the isolation of four prenylated benzoic acid derivatives (1-4). Four analogs (5-8) were synthesized. Seven compounds were found to significantly inhibit the catalytic activity of PL with IC50 values between 28.32 and 55.8 µM. On the other hand, only two compounds (6 and 7) were active as inhibitors of AG with IC50 values lower than 155 µM, standing out as the potential multitarget of these chromane compounds. Enzyme kinetics and molecular docking studies showed that the bioactive compounds mainly interact with amino acids other than those of the catalytic site in both PL and AG. This work constitutes the first report on the antidiabetic and antiobesity potential of substances derived from P. cumanense.

Consumption of cricket (Acheta domesticus) flour decreases insulin resistance and fat accumulation in rats fed with high-fat and -fructose diet.

The consumption of cricket (Acheta domesticus, AD) has recently increased due to its high nutritional and bioactive compound contents. However, limited studies have explored the beneficial effects of AD consumption. Therefore, we aimed to evaluate the protective effect of a diet supplemented with AD flour on obesity control and its complications in an in vivo model. The chemical profiling of the AD showed an important protein content, chitin, and polyunsaturated fatty acids contents. For the in vivo study, a high-fructose and saturated fat diet (HFFD) was supplemented with AD (4% and 8%). The 8% AD supplementation reduced body weight gain (19%) and serum triglycerides (37%) in HFFD-fed rats. These benefits were related to a greater lipid excretion in feces (97%) and the partial inhibition of pancreatic lipase in vitro by the aqueous extract and the hydrolyzed proteins obtained from AD. Additionally, the 8% AD supplementation improved insulin resistance measured by the HOMA index (61%). Thus, 8% AD supplementation to HFFD-fed rats was effective in preventing obesity, dyslipidemia, and insulin resistance. PRACTICAL APPLICATIONS: Obesity is a risk factor for developing insulin resistance and dyslipidemia. Therefore, there is an increasing interest in consuming foods rich in bioactive compounds as therapeutic alternatives for managing the development of obesity and its complications. Edible insects, such as crickets, are attractive for treating obesity due to their content of protein, fiber, and polyunsaturated fatty acids. Studies have explored the effect of glycosaminoglycan (GAG)-enriched extracts from the cricket Gryllus bimaculatus against obesity. However, GAG content in crickets is low, and crickets are commonly consumed whole instead of extracts. The cricket Acheta domesticus (AD) is among the most rearing cricket species as it is easy to farm and has a better flavor. However, limited studies have explored the beneficial effects of AD consumption. This study demonstrates that AD prevents obesity and ameliorates dyslipidemia and insulin resistance. Therefore, AD is a valuable entomotherapeutic strategy to reduce the comorbidities associated with diet-induced obesity.

Hydrolysates and peptide fractions from pork and chicken skin collagen as pancreatic lipase inhibitors.

The objective of this work was to obtain hydrolysates and peptide fractions from pork (PSC) and chicken (CSC) skin collagen extracts and to evaluate their ability as pancreatic lipase inhibitors. Collagen extracts were hydrolyzed with collagenase or a protease from Bacillus licheniformis (MPRO NX®) at 6, 12, and 24 h. After 24 h incubation, the highest degree of hydrolysis of PSC (p < 0.05) was obtained with collagenase (72.58%), while in CSC was obtained with MPRO NX® (64.45%). Hydrolysates obtained at 24 h had the highest inhibitory activity of lipase (p < 0.05). CSC/collagenase hydrolysates (10 mg/mL) presented the highest inhibitory activity (75.53%) (p < 0.05). Ultrafiltrated fractions >5 kDa from CSC/collagenase and PSC/MPRO NX® hydrolysates were the most bioactive fractions (IC50: 4.33 mg/mL). The highest were obtained by CSC peptides (IC50s: 6.30 and 6.08 mg/mL). These results may be considered as a novel approach to use collagen hydrolysates, or their peptide fractions, as promising natural inhibitors of pancreatic lipase.

Multitarget Action of Xanthones from Garcinia mangostana against α-Amylase, α-Glucosidase and Pancreatic Lipase.

Digestive enzymes such α-amylase (AA), α-glucosidase (AG) and pancreatic lipase (PL), play an important role in the metabolism of carbohydrates and lipids, being attractive therapeutic targets for the treatment of type 2 diabetes and obesity. Garcinia mangostana is an interesting species because there have been identified xanthones with the potential to inhibit these enzymes. In this study, the multitarget inhibitory potential of xanthones from G. mangostana against AA, AG and PL was assessed. The methodology included the isolation and identification of bioactive xanthones, the synthesis of some derivatives and a molecular docking study. The chemical study allowed the isolation of five xanthones (1-5). Six derivatives (6-11) were synthesized from the major compound, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle. Compounds with multitarget activity correspond to 2, 4, 5, 6 and 9, highlighting 6 with IC50 values of 33.3 µM on AA, 69.2 µM on AG and 164.4 µM on PL. Enzymatic kinetics and molecular docking studies showed that the bioactive xanthones are mainly competitive inhibitors on AA, mixed inhibitors on AG and non-competitive inhibitors on PL. The molecular coupling study established that the presence of methoxy, hydroxyl and carbonyl groups are important in the activity and interaction of polyfunctional xanthones, highlighting their importance depending on the mode of inhibition.

Effect of lipid source and emulsifier on productive and physiological parameters of broilers.

OBJECTIVE: This study aimed to evaluate the replacement of degummed soybean oil (DSO) by acid soybean oil (ASO) in diets with or without the inclusion of emulsifier on broiler performance, relative organ weight, lipase activity, intestinal morphometry, and nutrient digestibility. METHODS: A total of 704 1-day-old male broiler chicks were allotted to a 2×2 completely randomized factorial design (with or without emulsifier × two lipid sources [ASO and DSO]), with eight replicates and 22 birds each. The metabolizable energy level in diets with emulsifier was reduced by 40 kcal/kg from 1 to 21 d and 50 kcal/kg from 22 to 49 d. RESULTS: Broilers fed diets containing ASO without emulsifier had higher (p = 0.005) weight gain than DSO-fed animals and with the inclusion of emulsifier had worse (p = 0.018) feed conversion ratio (FCR). Birds fed diets with emulsifier worsened FCR regardless of lipid source from 1 to 21 days (p = 0.006) and from 1 to 49 days (p = 0.0002). There was an increase (p = 0.026) in the relative pancreas weight, at 14 days, in birds fed diets containing ASO. Lipase activity and morphometry of the duodenum and jejunum, at 14 and 21 days, were not affected (p>0.05). The dietary inclusion of emulsifier improved the digestible energy (p = 0.053) in the presence of ASO. For the digestibility coefficients (gross energy, crude protein, and mineral matter), no interference was observed (p>0.05). CONCLUSION: The inclusion of emulsifier to energy-restricted diet with ASO maintained broiler performance in the first week, but worsened FCR in subsequent phases. The ASO can be considered as an alternative lipid source to DSO and does not interfere with the morphophysiological characteristics and performance of broilers. The combination of ASO and emulsifier increased the digestible energy content by 6.2%.

Potential of Soy Gum Emulsification in Starter Diets for Broiler Chickens

This study evaluated the viability of using soy gum (residue from soy processing to obtain degummed oil) as an emulsifier in starter diets for broilers (1 to 21 days). For this, 600 1-day-old male broilers (Cobb® 500) were randomly assigned in a factorial arrangement (3 x 4), with three levels of gum inclusion (0, 1.25, and 2.5%) and four levels of soybean oil (0,1.3, 2.6, and 3.9%), with 5 replicates of 10 birds each. At 7, 14, and 21 days of age, we analyzed the performance parameters, pancreatic lipase activity and digestibility coefficients. Inclusion of soy gum improved (p<0.05) the performance and the digestibility coefficient of the ether extract, increased (p<0.05) the levels of AME and AMEn. The higher inclusion of gum (2.5%) as an emulsifier resulted in improved performance, showing the best values of feed conversion, with increased ether extract digestibility, increased AME content of the diets, and a lower requirement for pancreatic lipase in micelle formation.(AU)

Inhibition of α-glucosidase, pancreatic lipase, and antioxidant property of Myrcia hatschbachii D. Legrand containing gallic and ellagic acids / Inhibición de la α-glucosidasa, la lipasa pancreática y la propiedad antioxidante de Myrcia hatschbachii D. Legrand que contiene ácidos gálico y elágico

Several species of the Myrcia genus have been used in folk medicine to treat diabetes. Therefore, the aim of this work was to investigate the inhibitory activity of α-glucosidase and pancreatic lipase in the crude extract (EBF) and in the ethyl acetate fraction (FFA) of Myrcia hatschbachii, as well as to identify isolated phenolic compounds and to evaluate the antioxidant property and preliminary in vitro toxicity against Artemia salina. EBF (IC50: 3.21 µg/mL) and FFA (IC50: 1.14 µg/mL) showed inhibitory activity superior to acarbose (IC50: 193.65 µg/mL). In addition, they showed inhibitory effects of pancreatic lipase (IC50: 556.58 µg/mL for EBF and 532.68 µg/mL for FFA), antioxidant potential, absence of preliminary toxicity and presence of gallic andellagic acids in FFA. The relevant results in the inhibition of α-glucosidase and pancreatic lipase motivate new studies for the development of herbal medicines that assist in the treatment of diabetic patients.

Varias especies del género Myrcia se han utilizado en la medicina popular para tratar la diabetes. Por lo tanto, el objetivo de este trabajo fue investigar la actividad inhibitoria de la α-glucosidasa y la lipasa pancreática en el extracto crudo (EBF) y en la fracción de acetato de etilo (FFA) de Myrcia hatschbachii, así como identificar compuestos fenólicos aislados y evaluar la propiedad antioxidante y toxicidad in vitro preliminar contra Artemia salina. EBF (IC50: 3.21 µg/mL) y FFA (IC50: 1.14 µg/mL) mostraron una actividad inhibitoria superior a la acarbosa (IC50: 193.65 µg/mL). Además, mostraron efectos inhibitorios de la lipasa pancreática (IC50: 556.58 µg/mL para EBF y 532.68 µg/mL para FFA), potencial antioxidante, ausencia de toxicidad preliminar y presencia de ácidos gálico y elágico en FFA. Los resultados relevantes en la inhibición de la α-glucosidasa y la lipasa pancreática motivan nuevos estudios para el desarrollo de medicamentos a base de hierbas que ayudan en el tratamiento de pacientes diabéticos.

Do Flavonoids from Durum Wheat Contribute to Its Bioactive Properties? A Prospective Study.

A clear gap with respect to the potential biological properties of wheat flavonoids exists in the available literature. This information is crucial for breeding programs aiming to produce new varieties presenting improved health benefits. Accordingly, advanced breeding lines of whole durum wheat were evaluated in this contribution. The highest recovery of phenolics was achieved using aqueous acetone (50:50, v/v), as verified by multi-response optimization, thus showing that phenolics could be largely underestimated by employing an inappropriate extraction. The concentration of derivatives of apigenin, the main phenolics present, ranged from 63.5 to 80.7%, as evaluated by LC-ESI-QTOF-MS. Phenolics from the breeding line 98 exhibited the highest ability in scavenging peroxyl radicals, reducing power as well as in terms of inhibition of pancreatic lipase activity, a key enzyme regulating the absorption of triacylglycerols. In contrast, none of the samples exhibited a significant anti-diabetic potential. Despite their high concentration compared to that of phenolic acids, results of this work do not support a significant antioxidant and pancreatic lipase inhibitory effect of durum wheat flavonoids. Therefore, breeding programs and animal and/or human trials related to the effect of durum wheat flavonoids on oxidative stress and absorption of triacylglycerols are discouraged at this point.

Predisposition to acute pancreatitis in dogs with severe acute renal failure / Predisposição à pancreatite aguda em cães com insuficiência renal aguda grave

Patients with acute renal failure often have a negative energy balance, which promotes metabolic changes predisposing to complications. The objective of this study was to evaluate laboratory parameters of 30 dogs with severe acute renal failure, to assess their relationship with the possibility of developing acute pancreatitis due to the negative energy balance, and to correlate these findings with the degree of renal failure. Serum concentrations of urea, creatinine, beta-hydroxybutyrate, triglycerides, amylase, total lipase, and canine pancreatic lipase were compared between healthy dogs and dogs with severe acute renal failure. A greater serum concentration of beta-hydroxybutyrate and greater activity of pancreatic enzymes, particularly canine pancreatic lipase, as well as a stronger correlation between the latter and serum creatinine concentrations, were related to the occurrence of acute pancreatitis in patients with severe acute renal failure. A greater degree of renal failure implied a greater predisposition to acute pancreatitis.(AU)

O portador de insuficiência renal aguda é um paciente que, muitas vezes, encontra-se sob importante condição de balanço energético negativo, gerando alterações metabólicas que predispõem a complicações. O objetivo deste estudo foi avaliar parâmetros laboratoriais de trinta cães com insuficiência renal aguda grave, quanto a possibilidade de desenvolvimento de pancreatite aguda em função do balanço energético negativo, e relacioná-los ao grau de gravidade da insuficiência renal. As concentrações séricas de ureia, creatinina, betahidroxibutirato, triglicérides, amilase, lipase total e lipase pancreática canina foram comparadas entre o grupo de cães hígidos e o de cães doentes. Observou-se maior concentração sérica de betahidroxibutirato e maior atividade das enzimas pancreáticas, especialmente da lipase pancreática canina, além de forte correlação entre esta última e a concentração sérica de creatinina, demonstrando a ocorrência de pancreatite aguda em pacientes com insuficiência renal aguda grave. Verificou-se também que quanto mais grave é a insuficiência renal, maior é a predisposição à pancreatite aguda.(AU)

Predisposition to acute pancreatitis in dogs with severe acute renal failure

ABSTRACT: Patients with acute renal failure often have a negative energy balance, which promotes metabolic changes predisposing to complications. The objective of this study was to evaluate laboratory parameters of 30 dogs with severe acute renal failure, to assess their relationship with the possibility of developing acute pancreatitis due to the negative energy balance, and to correlate these findings with the degree of renal failure. Serum concentrations of urea, creatinine, beta-hydroxybutyrate, triglycerides, amylase, total lipase, and canine pancreatic lipase were compared between healthy dogs and dogs with severe acute renal failure. A greater serum concentration of beta-hydroxybutyrate and greater activity of pancreatic enzymes, particularly canine pancreatic lipase, as well as a stronger correlation between the latter and serum creatinine concentrations, were related to the occurrence of acute pancreatitis in patients with severe acute renal failure. A greater degree of renal failure implied a greater predisposition to acute pancreatitis.

RESUMO: O portador de insuficiência renal aguda é um paciente que, muitas vezes, encontra-se sob importante condição de balanço energético negativo, gerando alterações metabólicas que predispõem a complicações. O objetivo deste estudo foi avaliar parâmetros laboratoriais de trinta cães com insuficiência renal aguda grave, quanto a possibilidade de desenvolvimento de pancreatite aguda em função do balanço energético negativo, e relacioná-los ao grau de gravidade da insuficiência renal. As concentrações séricas de ureia, creatinina, betahidroxibutirato, triglicérides, amilase, lipase total e lipase pancreática canina foram comparadas entre o grupo de cães hígidos e o de cães doentes. Observou-se maior concentração sérica de betahidroxibutirato e maior atividade das enzimas pancreáticas, especialmente da lipase pancreática canina, além de forte correlação entre esta última e a concentração sérica de creatinina, demonstrando a ocorrência de pancreatite aguda em pacientes com insuficiência renal aguda grave. Verificou-se também que quanto mais grave é a insuficiência renal, maior é a predisposição à pancreatite aguda.

Predisposition to acute pancreatitis in dogs with severe acute renal failure / Predisposição à pancreatite aguda em cães com insuficiência renal aguda grave

Patients with acute renal failure often have a negative energy balance, which promotes metabolic changes predisposing to complications. The objective of this study was to evaluate laboratory parameters of 30 dogs with severe acute renal failure, to assess their relationship with the possibility of developing acute pancreatitis due to the negative energy balance, and to correlate these findings with the degree of renal failure. Serum concentrations of urea, creatinine, beta-hydroxybutyrate, triglycerides, amylase, total lipase, and canine pancreatic lipase were compared between healthy dogs and dogs with severe acute renal failure. A greater serum concentration of beta-hydroxybutyrate and greater activity of pancreatic enzymes, particularly canine pancreatic lipase, as well as a stronger correlation between the latter and serum creatinine concentrations, were related to the occurrence of acute pancreatitis in patients with severe acute renal failure. A greater degree of renal failure implied a greater predisposition to acute pancreatitis.(AU)

O portador de insuficiência renal aguda é um paciente que, muitas vezes, encontra-se sob importante condição de balanço energético negativo, gerando alterações metabólicas que predispõem a complicações. O objetivo deste estudo foi avaliar parâmetros laboratoriais de trinta cães com insuficiência renal aguda grave, quanto a possibilidade de desenvolvimento de pancreatite aguda em função do balanço energético negativo, e relacioná-los ao grau de gravidade da insuficiência renal. As concentrações séricas de ureia, creatinina, betahidroxibutirato, triglicérides, amilase, lipase total e lipase pancreática canina foram comparadas entre o grupo de cães hígidos e o de cães doentes. Observou-se maior concentração sérica de betahidroxibutirato e maior atividade das enzimas pancreáticas, especialmente da lipase pancreática canina, além de forte correlação entre esta última e a concentração sérica de creatinina, demonstrando a ocorrência de pancreatite aguda em pacientes com insuficiência renal aguda grave. Verificou-se também que quanto mais grave é a insuficiência renal, maior é a predisposição à pancreatite aguda.(AU)

Cocoa (Theobroma cacao L.) Seed Proteins' Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models.

The aim of this study was to determine the pancreatic lipase (PL) inhibitory effect of cocoa protein (CP) hydrolysates (CPH) using in silico and in vitro approaches, and an in vivo high-fat diet (HF) obese rat model. The results showed better theoretical affinity on PL for cocoa peptides EEQR, GGER, QTGVQ, and VSTDVNIE released from vicilin and albumins (-6.5, -6.3, -6.2, and -6.1 kcal/mol, respectively). Absorption, distribution, metabolism, and excretion (ADMET) prediction showed the human intestinal absorption (HIA) capacity of orlistat and eight cocoa peptides, demonstrating that they presented a low probability of toxicity with values lower than 0.6, while the orlistat has a high probability of hepatotoxicity with a mean value of 0.9. CPH (degree of hydrolysis of 55%) inhibited PL with an IC50 (concentration needed to inhibit 50% of enzyme activity) value of 1.38 mg/mL. The intragastric administration of 150 mg CP/kg/day to rats increased total lipids and triglycerides excretion in feces, ranging from 11% to 15% compared to the HF-diet. The HF + CP-diet also significantly decreased (p < 0.05) the apparent rate of fat absorption compared with the HF group. These results suggest that CP has anti-obesity potential by inhibiting PL, thus helping to prevent the development of non-communicable diseases.

Screening of Gastrointestinal Lipase Inhibitors Produced by Microorganisms Isolated from Soil and Lake Sediments.

Gastrointestinal lipase inhibitors are molecules of pharmaceutical interest due to their use as anti-obesity drugs. In this study, forty strains isolated from soil and sediments were identified with the ability to produce inhibition of gastrointestinal lipase activity. The biomass extract of these strains showed at least 50% inhibition in the hydrolysis of tributyrin by recombinant human pancreatic lipase (rHPL) or rabbit gastric lipase (RGL) by in vitro assays. Based on gene sequencing, the isolates were identified mainly as Streptomycetes. Moreover, none of the identified strains has been reported to be lipase inhibitor producers, so they can be viewed as potential sources for obtaining new drugs. IC50 values of the three best inhibitor extracts showed that AC104-10 was the most promising strain for production of gastrointestinal lipase inhibitors. AC104-10 shows 99% homology (16S rRNA gene fragment) to Streptomyces cinereoruber strain NBRC 12756. An inhibitory study over trypsin activity revealed that AC104-10 extract, as well as THL, had no significant effect on the activity of this protease, showing its specificity for lipases. In addition, analyzes by MALDI-TOF mass spectrometry of the enzyme-inhibitor complex revealed that there is a covalent interaction of the AC104-10 inhibitor with the catalytic serine of the pancreatic lipase, and that the molecular weight of the inhibitor is approximately 686.19 Da.

Antioxidant and anti-glycation capacities of some medicinal plants and their potential inhibitory against digestive enzymes related to type 2 diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants preparations are used by traditional medicine in the treatment of various diseases, such as type-2 diabetes mellitus. Some medicinal plants are capable of controlling the complications of this metabolic disease at different levels, for example, providing antioxidant compounds that act against oxidative stress and protein glycation and others which are capable of inhibiting the catalysis of digestive enzymes and thus contribute to the reduction of hyperglycemia and hyperlipidemia. Our objective was to investigate the antioxidant and anti-glycation activities of some medicinal plants and their potential inhibitory against α-amylase, α-glucosidase and pancreatic lipase activities. MATERIAL AND METHODS: Based on the ethnobotanical researches carried out by academic studies conducted at the Federal University of Uberlandia, ten plants traditionally used in the treatment of type-2 diabetes mellitus were selected. Ethanol (EtOH) and hexane (Hex) extracts of specific parts of these plants were used in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant (DPPH, ORAC and FRAP) and anti-glycation (BSA/fructose model) capacities. RESULTS: The results indicate that EtOH extract of four of the ten analyzed plants exhibited more than 70% of antioxidant and anti-glycation capacities, and α-amylase and lipase inhibitory activities; no extract was able to inhibit more than 40% the α-glucosidase activity. The EtOH extracts of Bauhinia forficata and Syzygium. cumini inhibited α-amylase (IC50 8.17 ± 2.24 and 401.8 ± 14.7 µg/mL, respectively), whereas EtOH extracts of B. forficata, Chamomilla recutita and Echinodorus grandiflorus inhibited lipase (IC50 59.6 ± 10.8, 264.2 ± 87.2 and 115.8 ± 57.1 µg/mL, respectively). In addition, EtOH extracts of B. forficata, S. cumini, C. recutita and E. grandiflorus showed, respectively, higher antioxidant capacity (DPPH IC50 0.7 ± 0.1, 2.5 ± 0.2, 1.3 ± 0.2 and 35.3 ± 9.0 µg/mL) and anti-glycation activity (IC50 22.7 ± 4.4, 246.2 ± 81.7, 18.5 ± 2.8 and 339.0 ± 91.0 µg/mL). CONCLUSIONS: EtOH extracts of four of the ten species popularly cited for treatment of type 2 diabetes mellitus have shown promising antioxidant and anti-glycation properties, as well as the ability to inhibit the digestive enzymes α-amylase and lipase. Thus, our results open new possibilities for further studies in order to evaluate the antidiabetic potential of these medicinal plants.