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Pancreatitis is a common, life-threatening inflammatory disease of the exocrine pancreas. Its pathogenesis remains obscure, and no specific or effective treatment is available. Gallstones and alcohol excess are major etiologies of pancreatitis; in a small portion of patients the disease is hereditary. Pancreatitis is believed to be initiated by injured acinar cells (the main exocrine pancreas cell type), leading to parenchymal necrosis and local and systemic inflammation. The primary function of these cells is to produce, store, and secrete a variety of enzymes that break down all categories of nutrients. Most digestive enzymes, including all proteases, are secreted by acinar cells as inactive proforms (zymogens) and in physiological conditions are only activated when reaching the intestine. The generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other zymogens. It was proposed that pancreatitis results from proteolytic autodigestion of the gland, mediated by premature/inappropriate trypsinogen activation within acinar cells. The intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis, and in human disease. On the basis of these observations, it has been considered the central pathogenic mechanism of pancreatitis - a concept with a century-old history. This review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis, particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis; analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its' damaging effects; discusses the gaps in our knowledge, potential therapeutic approaches, and directions for future research. We conclude that trypsin is not the culprit in the disease pathogenesis but, at most, a mediator of some pancreatitis responses. Therefore, the search for effective therapies should focus on approaches to prevent or normalize other intra-acinar pathologic processes, such as defective autophagy leading to parenchymal cell death and unrelenting inflammation., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Obesity is a chronic noncommunicable disease characterized by excessive body fat that can have negative health consequences. Obesity is a complex disease caused by a combination of genetic, environmental, and lifestyle factors. It is characterized by a discrepancy between caloric intake and expenditure. Obesity increases the risk of acquiring major chronic diseases, including heart disease, stroke, cancer, and Type 2 diabetes mellitus (T2DM). Currently, the inhibition of pancreatic lipases (PL) is a promising pharmacological therapy for obesity and weight management. In this study, the inhibition of pancreatic lipase by Cannabis sativa (C. sativa) plant extract and cannabinoids was investigated., Methods: The inhibitory effect was assessed using p-nitrophenyl butyrate (pNPB), and the results were obtained by calculating the percentage relative activity and assessed using one-way analysis of variance (ANOVA). Kinetic studies and spectroscopy techniques were used to evaluate the mode of inhibition. Diet-induced; and diabetic rat models were studied to evaluate the direct effects of C. sativa extract on PL activity., Results: Kinetic analyses showed that the plant extracts inhibited pancreatic lipase, with tetrahydrocannabinol (THC) and cannabinol (CBN) being the potential cause of the inhibition noted for the C. sativa plant extract. CBN and THC inhibited the pancreatic lipase activity in a competitive manner, with the lowest residual enzyme activity of 52 % observed at a 10 μg/mL concentration of CBN and 39 % inhibition at a 25 μg/mL concentration of THC. Circular dichroism (CD) spectroscopy revealed that the inhibitors caused a change in the enzyme's secondary structure. At low concentrations, THC showed potential for synergistic inhibition with orlistat. C.sativa treatment in an in vivo rat model confirmed its inhibitory effects on pancreatic lipase activity., Conclusion: The findings in this study provided insight into the use of cannabinoids as pancreatic lipase inhibitors and the possibility of using these compounds to develop new pharmacological treatments for obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Inhibition of pancreatic lipase (PL) is a strategy to prevent obesity. The inhibitory effects of Flos Sophorae Immaturus (FSI) extract and its main flavonoid components, rutin and quercetin, on PL were investigated. The contents of rutin and quercetin in FSI extract were 44.10 ± 1.33 % and 6.07 ± 1.62 %, respectively. The IC 50 values of FSI extract, rutin and quercetin on PL were 322, 258 and 71 μg/mL, respectively. Rutin and quercetin inhibited PL in a reversible and noncompetitive manner. The combination of rutin and quercetin exhibited synergistic inhibitory effects at low concentration. The binding of rutin/quercetin with PL caused the fluorescence quenching of protein. Fluorescence titration showed the binding affinity of quercetin with PL protein was stronger than that of rutin. Circular dichroism analysis showed the binding changed the secondary structure of PL with an increase in random coil and a decrease in α-Helix and β-Sheet. Molecular docking revealed that rutin and quercetin could interact with the amino acid residues around the catalytic site through multiple secondary interactions. In vivo studies showed that FSI extract can reduce fat absorption and promote fecal fat excretion through inhibition of PL activity, and the effects were mainly due to rutin and quercetin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

This study examined the suppressive effects of 16 selected plant-based foods on α-glucosidase and pancreatic lipase and their antioxidant properties. Among these, the bark of Cinnamomum cassia (Cinnamon, WLN-FM 15) showed the highest inhibitory activity against α-glucosidase and the highest antioxidant activity. Additionally, WLN-FM 15 showed promising results in the other tests. To further identify the bioactive constituents of WLN-FM 15, a multi-bioactivity-labeled molecular networking approach was used through a combination of GNPS-based molecular networking, DPPH-HPLC, and affinity-based ultrafiltration-HPLC. A total of nine procyanidins were identified as antioxidants and inhibitors of α-glucosidase and pancreatic lipase in WLN-FM 15. Subsequently, procyanidins A1, A2, B1, and C1 were isolated, and their efficacy was confirmed through functional assays. In summary, WLN-FM 15 has the potential to serve as a functional food ingredient with the procyanidins as its bioactive constituents. These results also suggest that the multi-bioactivity-labeled molecular networking approach is reliable for identifying bioactive constituents in plant-based foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.

The discovery of pancreatic lipase (PL) inhibitors is an essential route to develop new anti-obesity drugs. In this experiment, chitosan was used to add amino groups to cellulose filter paper (CFP) and then glutaraldehyde was used to covalently combine PL with amino-modified CFP through the Schiff base reaction. Under optimal immobilization conditions, CFP immobilized PL has a wide range of pH and temperature tolerance, as well as excellent reproducibility, reusability and storage stability. Subsequently, 26 natural products (NPs) were screened by immobilized PL with black tea extract having the highest inhibition rate. Three compounds with binding effects on PL (epigallocatechin gallate, theaflavin-3-gallate and theaflavin-3,3'-digallate) were captured. Molecular docking proved that these three compounds have a strong binding affinity for PL. Fluorescence spectra further revealed that theaflavin-3,3'-digallate could statically quench the intrinsic fluorescence of pancreatic lipase. The molecular docking and thermodynamic parameters indicated that electrostatic interaction was considered as the main interaction force between PL and theaflavin-3,3'-digallate. Finally, the potential anti-obesity targets and pathways of the three compounds were discussed through network pharmacology. This study not only proposes a simple and efficient method for screening PL inhibitors, but also sheds light on the anti-obesity mechanism of active compounds in black tea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The detailed characterization of the structural features of peptides targeting cholesterol esterase (CEase) or pancreatic lipase (PPL) will benefit the management of hyperlipidemia and obesity. This study employed the Glide SP (standard precision)-peptide method to predict the binding modes of 20 2 dipeptides and 20 3 tripeptides to these targets, correlating residue composition and position with binding energy. Strong preferences for Trp, Phe, and Tyr were observed at all positions of potential inhibitory peptides, whereas negatively charged residues Glu and Asp were disfavored. Notably, Arg and aromatic rings significantly influenced the peptide conformation at the active site. Tripeptide IWR demonstrated the high efficacy, with IC 50 values of 0.214 mg/mL for CEase and 0.230 mg/mL for PPL. Five novel IWR scaffold-tetrapeptides exhibited promising inhibitory activity. Non-covalent interactions and energy contributions dominated the formation of stable complexes. Our results provide insights for the development of new sequences or peptide-like molecules with enhanced inhibitory activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

A variety of therapeutic possibilities have emerged for skillfully regulating protein function or conformation through intermolecular interaction modulation to rectify abnormal biochemical reactions in diseases. Herein, a devised strategy of enzyme coordinators has been employed to alleviate postoperative pancreatic fistula (POPF), which is characterized by the leakage of digestive enzymes including trypsin, chymotrypsin, and lipase. The development of a dextrorotary (D)-peptide supramolecular gel (CP-CNDS) under this notion showcases its propensity for forming gels driven by intermolecular interaction. Upon POPF, CP-CNDS not only captures enzymes from solution into hydrogel, but also effectively entraps them within the internal gel, preventing their exchange with counterparts in the external milieu. As a result, CP-CNDS completely suppresses the activity of digestive enzymes, effectively alleviating POPF. Remarkably, rats with POPF treated with CP-CNDS not only survived but also made a recovery within a mere 3-day period, while mock-treated POPF rats had a survival rate of less than 5 days when experiencing postoperative pancreatic fistula, leak or abscess. Collectively, the reported CP-CNDS provides promising avenues for preventing and treating POPF, while exemplifying precision medicine-guided regulation of protein activity that effectively targets specific pathogenic molecules across multiple diseases., (© 2024. The Author(s).)

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC 50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Our prior results showed that an acute bout of endurance exercise for 6 h, but not 1 h, decreased pancreatic amylase activity, indicating that acute endurance exercise may affect carbohydrate digestive capacity in an exercise duration-dependent manner. Here, we investigated the effects of acute endurance exercise of different intensities on mouse pancreatic amylase activity. Male C57BL/6J mice performed low- or high-intensity running exercise for 60 min at either 10 (Ex-Low group) or 20 m/min (Ex-High group). The control group comprised sedentary mice. Immediately after acute exercise, pancreatic amylase activity was significantly decreased in the Ex-High group and not the Ex-Low group in comparison with the control group. To determine whether the decreased amylase activity induced by high-intensity exercise influenced muscle glycogen recovery after exercise, we investigated the rates of muscle glycogen resynthesis in Ex-High group mice administered either oral glucose or starch solution (2.0 mg/g body weight) immediately after exercise. The starch-fed mice exhibited significantly lower post-exercise glycogen accumulation rates in the 2-h recovery period compared with the glucose-fed mice. This difference in the glycogen accumulation rate was absent for starch- and glucose-fed mice in the sedentary (no exercise) control group. Furthermore, the plasma glucose AUC during early post-exercise recovery (0-60 min) was significantly lower in the starch-fed mice than in the glucose-fed mice. Thus, our findings suggest that acute endurance exercise diminishes the carbohydrate digestive capacity of the pancreas in a manner dependent on exercise intensity, with polysaccharides leading to delayed muscle glycogen recovery after exercise., Competing Interests: The authors have no conflicts of interest to disclose.

Human pancreatic lipase (hPL) is a vital digestive enzyme responsible for breaking down dietary fats in humans, inhibiting hPL is a feasible strategy for preventing and treating obesity. This study aims to investigate the structure-activity relationships (SARs) of flavonoids as hPL inhibitors, and to find potent hPL inhibitors from natural and synthetic flavonoids. In this work, the anti-hPL effects of forty-nine structurally diverse naturally occurring flavonoids were assessed and the SARs were summarized. The results demonstrated that the pyrogallol group on the A ring was a key moiety for hPL inhibition. Subsequently, a series of baicalein derivatives were synthesized, while 4'-amino baicalein (ABA) and 4'-pyrrolidine baicalein (PBA) were identified as novel potent hPL inhibitors (IC 50  < 1 μM). Further investigations showed that scutellarein, ABA and PBA potently inhibited hPL in a non-competitive manner (K i  < 1 μM). Among all tested flavonoids, PBA showed the most potent anti-hPL effect in vitro, while this agent also exhibited favorable safety profiles, unique tissue distribution (high exposure level to intestinal system but low exposure levels to deep organs) and impressive in vivo effects for lowering blood triglyceride levels in mice. Collectively, this work uncovers the SARs of flavonoids against hPL, while a newly synthetic flavonoid (PBA) emerges as a potent hPL inhibitor with favorable safety profiles and impressive anti-hPL effects in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Obesity has become a significant global health concern, affecting millions of people worldwide. One well-studied approach to identifying potential anti-obesity agents is the inhibition of pancreatic lipase (PL), an enzyme responsible for dietary fat digestion. This study investigated the inhibitory effects and mechanisms of galactolipid monogalactosyldiacylglycerol (MGDG), that was extracted from Brassica rapa ssp. chinensis on PL. Five different MGDG compounds were isolated and the results showed that compounds containing shorter fatty acid side chains and a higher degree of unsaturated bonds exhibit a greater inhibition effect on PL. Interestingly, both the kinetic study and the molecular docking prediction revealed a non-competitive inhibition of MGDG. Furthermore, the in vitro digestion model also showed that the consumption of MGDG extract with salad dressing was effective in delaying enzymatic fat digestion in a dose-dependent manner. These results suggest that MGDG from Brassica rapa ssp. chinensis may be a promising candidate for developing novel anti-obesity therapies.

Background and Aims: To develop a model that describes how the pancreas functions, how the rate of synthesis of digestive enzymes is regulated, and finally what puts the pancreas to rest between meals., Methods: We applied the principals of control theory to previously published canine data to develop a model for how the canine pancreas functions. Using this model, we then describe the steps needed to apply this model to the human pancreas., Results: This new closed-loop negative feedback model describes what regulates digestive enzyme synthesis. This model is based on basolateral exocytosis of butyrylcholinesterase (BCHE) into the interstitial space. It is this level of BCHE * BCHE activity that controls the rate of canine pancreas digestive enzyme synthesis, and in the absence of stimulation from the vagus nerve, puts the pancreas to rest between meals., Conclusions: Finding secretagogue-specific inhibitory enzymes in the human pancreas that are analogous to BCHE in the canine, and blocking its associated receptors, may lead to a cure for human pancreatitis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The purpose of this review was to analyze the scientific literature on exocrine pancreatic insufficiency (EPI) in dogs and cats and our own research on porcine model to compare animal- and microbial-derived enzymes in the treatment of animals with this disease. Clinical signs of EPI occur when more than 85% of the pancreatic parenchyma is non-functional. EPI can be a consequence of various diseases. The insufficient activity or deficiency of pancreatic enzymes leads to impaired digestion and absorption, and consequently, to malnutrition. The primary treatment for enzyme insufficiency is pancreatic enzyme replacement therapy (PERT). PERT in animals with EPI is a lifetime therapy. Most commercially available products are of animal origin (processed pancreata obtained from a slaughter house) and contain lipases, alpha-amylase, and proteases. Enzymes of microbial and plant origin seem to be a promising alternative to animal-derived enzymes, but to date there are no registered preparations containing all enzymes simultaneously for use in clinical practice to treat EPI. Results from some previous studies have highlighted the "extra-digestive" functions of pancreatic enzymes, as well as the actions of pancreatic-like microbial enzymes. For example, trypsin activates protease-activated receptor and provokes maturation of enterocytes and enterostatin inhibits fat absorption. It has been postulated that intrapancreatic amylase is the main component of the acini-islet-acinar axis-the reflex which down regulates insulin release, while gut and blood amylase exhibit anti-incretin actions "per se." Additionally, high but still physiological blood amylase activity coincide with physiological glucose homeostasis and a lack of obesity., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Type 1 (T1D) and type 2 (T2D) diabetes lead to an aberrant metabolism of sialoglycoconjugates and elevated free serum sialic acid (FSSA) level. The present study evaluated sialidase and sialyltranferase activities in serum and some organs relevant to diabetes at early and late stages of T1D and T2D., Methods: Sialic acid level with sialidase and sialyltransferase activities were monitored in the serum, liver, pancreas, skeletal muscle and kidney of diabetic animals at early and late stages of the diseases., Results: The FSSA and activity of sialidase in the serum were significantly increased at late stage of both T1D and T2D while sialic acid level in the liver was significantly decreased in the early and late stages of T1D and T2D, respectively. Furthermore, the activity of sialidase was significantly elevated in most of the diabetes-relevant organs while the activity of sialyltransferase remained largely unchanged. A multiple regression analysis revealed the contribution of the liver to the FSSA while pancreas and kidney contributed to the activity of sialidase in the serum., Conclusions: We concluded that the release of hepatic sialic acid in addition to pancreatic and renal sialidase might (in)directly contribute to the increased FSSA during both types of diabetes mellitus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Erhabor, Obochi, Isah, Usman, Umar, Simelane, Shuaibu, Islam and Ibrahim.)

The inhibitory effects of twenty-six ginsenosides on human pancreatic lipase (hPL) and porcine pancreatic lipase (pPL) were studied. Study reveals that nine ginsenosides have moderate inhibitory effects against hPL, and good selectivity over pPL. By contrast, (S)-Rh2 showed good inhibitory effects on pPL over hPL. SAR analysis indicated that introduction of the O-glycosyl group(s) at C-3/C-7 site is unbeneficial for hPL inhibition, ginsenosides with A-skeleton is more beneficial than ginsenosides with B-/C-skeleton. Inhibition kinetic analysis indicated that Rg3 and (S)-Rh2 inhibited hPL-catalyzed DDAO-ol hydrolysis in a mixed manner. Molecular docking studies have confirmed that Rg3 and (S)-Rh2 inhibit hPL via many Pi-hydrogen interactions and hydrogen bonds with catalytic residues of hPL. These results indicated that pPL as an enzyme source could not fully represent the inhibitory effect of the tested compounds on hPL, and hPL should be used as far as possible to evaluate the inhibitory effect of PL.

Objective: Assess markers for pancreatic function and gastrointestinal malabsorption in African painted dogs (Lycaon pictus), including canine trypsin-like immunoreactivity (cTLI), canine pancreatic lipase immunoreactivity (cPLI), cobalamin, and folate at one North American facility., Animals: 15 healthy African painted dogs held at one institution were sampled during routine health examinations., Methods: Blood was collected at routine health examinations, and serum was separated and stored until testing. Serum was analyzed for cTLI, cPLI, cobalamin, and folate. The results were evaluated for correlation to sex, age, and storage time of samples., Results: All individuals had cTLI and folate levels below normal reference ranges for domestic dogs (< 5.0 µg/L and < 7.7 µg/L, respectively). Cobalamin values were within or above reported domestic dog ranges, and cPLI values were within range as well. No analytes were significantly influenced by sex or time in storage, while cTLI was positively correlated with age., Clinical Relevance: cTLI and folate did not fall within normal domestic canid reference ranges in this population of healthy African painted dogs. Clinical interpretation of these values based on domestic canid recommendations would indicate clinical disease, which was not apparent in this population. Analytes for pancreatic function and malabsorption or gastrointestinal indicators, including cTLI, cPLI, and folate, in African painted dogs should be interpreted with caution when using domestic dog references ranges.

Background: It is unknown if serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin-like immunoreactivity (cTLI) obtained postprandially are equivalent to measurements obtained after withholding food in dogs with suspected gastrointestinal disease., Hypothesis/objectives: Measurements of serum concentrations of cobalamin, folate, cPLI, and cTLI postprandially will be equivalent to measurements after 12 hours of withholding food in dogs with signs of chronic gastrointestinal disease. Changes observed will not alter clinical interpretation., Animals: 51 client-owned dogs with signs of gastrointestinal disease., Methods: Prospective single arm clinical trial. Serum concentrations of cobalamin, folate, cPLI and cTLI 2, 4, and 8 hours postprandially were compared by equivalence testing to values after withholding food for 12 hours (baseline)., Results: Mean serum cobalamin concentrations 2 hours (498.1 ± 213.1 ng/L; P = 0.024) and 4 hours (501.9 ± 207.4 ng/L; P = 0.008) postprandial were equivalent to baseline (517.3 ± 211.5 ng/L). Mean serum cTLI 2 hours (31.3 ± 14 μg/L; P < 0.001) and 4 hours (29.6 ± 13.1 μg/L; P = 0.027) postprandial were equivalent to baseline (31.1 ± 15 μg/L). Mean serum folate concentration 2 hours postprandial (15 ± 7.7 μg/L) was equivalent to baseline (13.7 ± 8.3 μg/L; P < 0.001). Equivalence could not be assessed for cPLI due to results below the lower limit of quantification. Feeding altered the clinical interpretation in 27% (cobalamin), 35% (folate), 20% (cTLI), and 12% (cPLI) of dogs., Conclusions and Clinical Importance: The clinical interpretation for a substantial number of samples changed after feeding, therefore withholding food before sample collection is prudent., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC 50 values of 0.26 ± 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the α-helix content and increasing the β-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor., (© 2024 John Wiley & Sons Ltd.)

To further enhance the application of nobiletin (an important active ingredient in Citrus fruits), we used ultrasonic homogenization-assisted antisolvent precipitation to create ultrafine particles of nobiletin (UPN). DMSO was used as the solvent, and deionized water was used as the antisolvent. When ultrasonication (670 W) and homogenization (16000 r/min) were synergistic, the solution concentration was 57 mg/mL, and the minimum particle size of UPN was 521.02 nm. The UPN samples outperformed the RN samples in terms of the inhibition of porcine pancreatic lipase, which was inhibited (by 500 mg/mL) by 68.41 % in the raw sample, 90.34 % in the ultrafine sample, and 83.59 % in the positive control, according to the data. Fourier transform infrared spectroscopy analysis revealed no chemical changes in the samples before or after preparation. However, the crystallinity of the processed ultrafine nobiletin particles decreased. Thus, this work offers significant relevance for applications in the realm of food chemistry and indirectly illustrates the expanded application potential of nobiletin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Early diagnosis of canine pancreatitis is challenging due to non-specific clinical signs. Currently, abdominal ultrasonography and measurement of canine pancreatic lipase (cPL) have been employed for the diagnosis of pancreatitis., Objective: Many qualitative and quantitative commercial cPL tests have been developed and used in veterinary clinics. This study aimed to compare three different methodologies SNAP cPL, Spec cPL, and Vcheck cPL tests to assess the concordance of these assays., Methods: Fifty serum samples were collected from 36 dogs with or without pancreatitis and subjected to SNAP cPL, Spec cPL, and Vcheck cPL tests. Agreement and correlation coefficients were calculated between the test results, and correlations were determined during the management of the patients., Results: The results of the three cPL assays were strongly correlated in 47/50 serum samples (94%). Cohen's kappa analysis between the Spec cPL and Vcheck cPL showed near perfect agreement (κ = 0.960, p < 0.001), SNAP cPL and Vcheck cPL (κ = 0.920, p < 0.001), and Spec cPL and SNAP cPL (κ = 0.880, p < 0.001). The correlation coefficients ( r ) between data from Spec cPL and Vcheck cPL tests was calculated by Spearman's correlation test ( r = 0.958, p < 0.001). Furthermore, the patterns of change in serum cPL concentrations determined using Spec cPL and Vcheck cPL were significantly consistent during the monitoring period in 11 patients., Conclusions and Relevance: Our data illustrated that Spec cPL and Vcheck cPL tests are compatible for clinical use in the diagnosis and monitoring of canine pancreatitis., Competing Interests: Jungho Kim and Soungjin Ji are the Director and Associate Director of the R&D department of Bionote Inc., respectively. The remaining authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Background: Corticosteroids are among the most commonly used drugs in cats and are increasingly discussed as a treatment for feline pancreatitis. However, its effects on serum lipase in healthy cats remain unknown., Objectives: To evaluate the effects of prednisolone on serum lipase activity and pancreatic lipase immunoreactivity (PLI) in cats., Animals: Seven clinically healthy colony cats, aged 4 to 7 years, with unremarkable CBC/biochemistry panel were studied., Methods: Prospective study: Prednisolone (1.1-1.5 mg/kg, median 1.28 mg/kg PO) was given daily for 7 consecutive days. Lipase activity (LIPC Roche; RI, 8-26 U/L) and PLI (Spec fPL; RI, 0-3.5 μg/L) were determined at day 1 before first treatment and at days 2, 3, 8, 10, and 14. Cats were examined daily. An a priori power analysis indicated that 6 cats were needed to find a biological relevant effect at 1-β = 0.8. Statistical analyses comprised the Friedman test, random intercept regression, and repeated-measures linear regression., Results: Median (range) day 1 lipase activities and PLI were 22 U/L (14-52 U/L) and 3.2 μg/L (2.3-15.7 μg/L). One cat with abnormally high lipase activity (52 U/L) and PLI (15.7 μg/L) at day 1 continued having elevated lipase activities and PLI throughout the study. Lipase activities and PLI concentrations did not differ significantly among time points regardless of whether the cat with elevated values was included or not. All cats remained healthy throughout the study., Conclusions and Clinical Importance: Administration of prednisolone in anti-inflammatory doses does not significantly increase serum lipase activity and PLI concentration., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Obesity is a disease of epidemic proportions with a concerning increasing trend. Regarded as one of the main sources of energy, lipids can also represent a big part of an unnecessary intake of calories and be, therefore, directly related to the problem of obesity. Pancreatic lipase is an enzyme that is essential in the absorption and digestion of dietary fats and has been explored as an alternative for the reduction of fat absorption and consequent weigh loss. Literature describes a great variability of methodologies and experimental conditions used in research to evaluate the in vitro inhibitory activity of compounds against pancreatic lipase. However, in an attempt to choose the best approach, it is necessary to know all the reaction conditions and understand how these can affect the enzymatic assay. The objective of this review is to understand and summarize the methodologies and respective experimental conditions that are mainly used to evaluate pancreatic lipase catalytic activity. 156 studies were included in this work and a detailed description of the most commonly used UV/Vis spectrophotometric and fluorimetric instrumental techniques are presented, including a discussion regarding the differences found in the parameters used in both techniques, namely enzyme, substrate, buffer solutions, kinetics conditions, temperature and pH. This works shows that both UV/Vis spectrophotometry and fluorimetry are useful instrumental techniques for the evaluation of pancreatic lipase catalytic activity, presenting several advantages and limitations, which make the choice of parameters and experimental conditions a crucial decision to obtain the most reliable results.

Alpha-amylase is the main enzyme for starch digestion in the mammalian gastrointestinal tract. There are species differences in the enzymatic activity of pancreatic amylase that are related to the digestive strategy and natural diet of a species. This aspect is well investigated in pet and farm animals, while in common laboratory animal rodents, information is scarce. In the context of the 3R concept, detailed knowledge of the digestive physiology should be the basis of adequate nutrition, experimental planning and data interpretation. The present study aimed to obtain reference data on amylase activity in pancreatic tissue and duodenal digesta in laboratory mice, rats and hamsters. In addition, digesta was stained with Lugol's iodine to visualize starch in the process of degradation throughout the gastrointestinal tract. Amylase activity in pancreatic tissue and duodenal digesta was significantly lower in hamsters than rats and mice. The Lugol staining showed intense starch degradation in the hamsters' forestomachs, presumably by microbial fermentation. A possible explanation is that the prae-duodenal microbial starch fermentation enhances digestibility and reduces the need for pancreatic amylase in hamsters. Rats and mice may rely more on pancreatic amylase for prae-caecal starch digestion, while the microbial fermentation is mainly located in the caecum. The results clearly show species differences in the digestive capacity for starch in mice, rats and hamsters that need to be considered in the feeding of these species in the laboratory setting as well as in the use of rodents as translational animal models., (© 2023. Springer Nature Limited.)

Background and Aim: Some patients with functional gastrointestinal disorders exhibit pancreatic dysfunctions and pancreatic enzyme abnormalities. Thus, we aimed to clarify whether significant differences in clinical characteristics, prevalence of pancreatic enzyme abnormalities, duodenal inflammation, and protease-activated receptor 2 (PAR2) expression levels related to hypersensitivity exist between functional dyspepsia (FD) alone and FD-irritable bowel syndrome (IBS) overlap group., Methods: Ninety-three patients based on the Rome IV criteria, FD alone (n = 44) and FD overlapped with IBS (n = 49) group were enrolled. The patients scored their own clinical symptoms after consuming high-fat meals. Serum trypsin, PLA2, lipase, p-amylase, and elastase-1 levels were measured. PAR2, eotaxin-3, and TRPV4 mRNA levels in duodenum were determined using real-time polymerase chain reaction methods. PRG2- and PAR2 in the duodenum were evaluated using immunostaining., Results: FD score and global GSRS in patients with FD-IBS overlap were significantly higher than FD alone. Although the prevalence of pancreatic enzyme abnormalities in patients with FD alone was significantly (P < 0.01) higher than that in FD-IBS overlap, the ratio of aggravation of clinical symptoms following high-fat intake in patients with FD-IBS overlap was significantly higher (P = 0.007) than that in patients with FD alone. PAR2- and PRG2-double positive cells were localized in the degranulated eosinophils in the duodenum of patients with FD-IBS overlap. The number of PAR2- and PRG2-double positive cells in FD-IBS overlap was significantly (P < 0.01) higher than FD alone., Conclusions: Pancreatic enzyme abnormalities and PAR2 expression on degranulated eosinophils infiltrations in the duodenum may be associated with the pathophysiology of patients with FD-IBS overlap in Asian populations., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Three new acetylenic aromatic compounds, sterehirsutynes A-C ( 1 - 3 ), along with three known congeners, frustulosinol ( 4 ), vibrayne ( 5 ), and sterehirsutinol ( 6 ), were isolated from the culture broth of Stereum hirsutum . Their structures were determined by detailed analyses of NMR and high-resolution mass. Chiral column analysis showed that compounds 2 and 3 were racemic mixtures. These new compounds were evaluated for porcine pancreatic lipase (PPL) inhibitory activities, and compounds 1 and (±) 3 showed moderate inhibitory activity against PPL, with IC 50 values of 23.2 ± 1.04 and 21.8 ± 2.15 μM, respectively.

Pancreatic lipase (PL) is a well-known key target for the prevention and treatment of obesity. Human carboxylesterase 1A (hCES1A) has become an important target for the treatment of hyperlipidaemia. Thus, the discovery of potent dual-target inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory effects against PL and hCES1A, and highly selectivity over hCES2A. Subsequently, a number of compounds based on the OA and UA skeletons were synthesised and evaluated. Structure-activity relationship (SAR) analysis of these compounds revealed that the acetyl group at the C-3 site of UA (compound 41 ) was very essential for both PL and hCES1A inhibition, with IC 50 of 0.75 µM and 0.014 µM, respectively. In addition, compound 39 with 2-enol and 3-ketal moiety of OA also has strong inhibitory effects against both PL and hCES1A, with IC 50 of 2.13 µM and 0.055 µM, respectively. Furthermore, compound 39 and 41 exhibited good selectivity over other human serine hydrolases including hCES2A, butyrylcholinesterase (BChE) and dipeptidyl peptidase IV (DPP-IV). Inhibitory kinetics and molecular docking studies demonstrated that both compounds 39 and 41 were effective mixed inhibitors of PL, while competitive inhibitors of hCES1A. Further investigations demonstrated that both compounds 39 and 41 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. Collectively, we found two triterpenoid derivatives with strong inhibitory ability on both PL and hCES1A, which can be served as promising lead compounds for the development of more potent dual-target inhibitors targeting on PL and hCES1A.

The proper balance of synthesis, folding, modification, and degradation of proteins, also known as protein homeostasis, is vital to cellular health and function. The unfolded protein response (UPR) is activated when the mechanisms maintaining protein homeostasis in the endoplasmic reticulum become overwhelmed. However, prolonged or strong UPR responses can result in elevated inflammation and cellular damage. Previously, we discovered that the enzyme filamentation induced by cyclic-AMP (Fic) can modulate the UPR response via posttranslational modification of binding immunoglobulin protein (BiP) by AMPylation during homeostasis and deAMPylation during stress. Loss of fic in Drosophila leads to vision defects and altered UPR activation in the fly eye. To investigate the importance of Fic-mediated AMPylation in a mammalian system, we generated a conditional null allele of Fic in mice and characterized the effect of Fic loss on the exocrine pancreas. Compared to controls, Fic -/- mice exhibit elevated serum markers for pancreatic dysfunction and display enhanced UPR signaling in the exocrine pancreas in response to physiological and pharmacological stress. In addition, both fic -/- flies and Fic -/- mice show reduced capacity to recover from damage by stress that triggers the UPR. These findings show that Fic-mediated AMPylation acts as a molecular rheostat that is required to temper the UPR response in the mammalian pancreas during physiological stress. Based on these findings, we propose that repeated physiological stress in differentiated tissues requires this rheostat for tissue resilience and continued function over the lifetime of an animal.

Objectives: Patients with short bowel syndrome (SBS) can have a high morbidity rate. To minimize morbidity, enteral autonomy is the primary goal in clinical management of patients with SBS. This is often difficult to achieve because of significant malabsorption. To date, there are limited therapies that improve absorption in patients with SBS. The impact of pancreatic enzyme replacement treatment on enteral absorption has not been studied in this population and was the primary aim of this study., Subjects/methods: This was an interventional study in 11 subjects (6 pediatric subjects ages 4.0-17.9 years, 5 adult subjects 18-75 years) that compared enteral absorption in each subject before and after pancreatic enzyme medication (Creon). Coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) were used as markers of enteral absorption of fat and protein, respectively., Results: There was no statistically significant mean change in CFA and CNA before and after pancreatic enzyme medication therapy. Six subjects demonstrated an increase in CFA and 8 subjects demonstrated an increase in CNA after the use of pancreatic enzyme medication therapy., Conclusions: There was no statistically significant improvement in enteral fat and protein absorption in the cohort as a whole, though several subjects demonstrated an improvement. These results suggest that some patients with SBS may benefit from treatment with pancreatic enzymes. Further studies are needed to better evaluate the effect of pancreatic enzyme therapy on enteral absorption in subjects with SBS and to characterize factors that may predict a positive response., Competing Interests: V.A.S. reports consulting with AbbVie on unrelated topics. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Lipases are water-soluble enzymes that hydrolyze water-insoluble lipid molecules, such as triglycerides, phospholipids, and galactolipids. They are ubiquitous in nature and are present in humans, animals, insects, plants, fungi, and microorganisms. While we commonly consider pancreatic lipase, this review provides an overview of several lipases that are important for the digestion and metabolism of lipids in veterinary species. All of these enzymes have specific functions but share a common α/β-hydrolase fold and a catalytic triad where substrate hydrolysis occurs. The pancreatic lipase gene family is one of the best characterized lipase gene families and consists of 7 mammalian subfamilies: pancreatic lipase, pancreatic lipase related proteins 1 and 2, hepatic lipase, lipoprotein lipase, endothelial lipase, and phosphatidylserine phospholipase A1. Other mammalian lipases that play integral roles in lipid digestion include carboxyl ester lipase and gastric lipase. Although most enzymes have preferred substrate specificity, much overlap occurs across the plethora of lipases because of the similarities in their structures. This has major implications for the development and clinical utilization of diagnostic assays. These implications are further explored in our companion Currents in One Health article by Lim et al in the August 2022 issue of the Journal of American Veterinary Medical Association, which focuses on pancreatic lipase assays for the diagnosis of pancreatitis.

The effect of different feeding regimes on the circadian rhythms of pancreatic digestive enzyme activities was evaluated in Mugil cephalus fry weighting 0.34 ± 0.01 g. Feeding regimes (feeding ration = 3% stocked biomass) differed on the number of meals offered per day: one, two and ten meals per day (R1, R2 and R3, respectively). The number of meals per day affected somatic growth; in particular, fry from the R3 group (0.80 ± 0.01 g) grew better than their congeners from R2 (0.70 ± 0.01 g) and R1 (0.63 ± 0.01 g) groups (P < 0.05). Feeding behaviour was modulated by the feeding regime, being the maximal gut fullness values found just after meal distribution in R1 and R2 groups, whereas this trend was not observed when feed was offered continuously during light hours (R3). Fry from R1 and R2 groups showed hyperphagia as they tended to store in their gut as much as possible feed particles to be later digested due to the limited daily meals. This strategy negatively affected feed digestion due to inappropriate enzyme to substrate ratio, changes in digestive enzyme activities and chyme transit times, which ultimately impaired growth performance. Enzyme activities were modulated by the number of meals, the more frequent the meals offered, the lower enzyme activities, supporting the hypothesis that digestive function is adapted to obtain a maximum benefit of the ingested nutrients. Present results showed that feeding grey mullet fry continuously during day light hours optimized feed digestion and promoted fry growth., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Acute pancreatitis (AP) is a common serious acute condition of the digestive system that remains a clinical challenge. Severe acute pancreatitis (SAP) in particular is characterized by high morbidity and mortality. The present study was designed to investigate the protective effect of Galangin (Gal), a natural flavonol obtained from lesser galangal, on L-arginine-induced SAP in mice and in AR42J cells. Amylase and lipase activities were measured and the histopathology of the pancreas, lung, and kidney was evaluated. Inflammation and oxidative stress were assessed using ELISA, western blotting, RT-PCR, and immunohistochemistry. Gal was shown to reduce proinflammatory cytokine production and reactive oxygen species (ROS) generation in vivo and in vitro. L-arginine treatment reduced the expression of components of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and the downstream protein heme oxygenase-1 (HO-1) in mice, whereas Gal increased their expression. Furthermore, the Nrf2/HO-1 pathway inhibitor brusatol prevented the anti-inflammatory and antioxidant effects of Gal in mice with SAP. Taken together, our results imply that Gal has protective effects in L-arginine-induced SAP that are induced by the upregulation of the Nrf2/HO-1 pathway, which has anti-inflammatory and antioxidant effects. Thus, Gal may represent a promising treatment for SAP., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Type 2 Diabetes mellitus is a chronic disease considered one of the most severe global health emergencies. Chlorogenic acid (1) has been shown to delay intestinal glucose absorption by inhibiting the activity of α-glucosidase (α-Glu) and α-amylase (α-Amy). In the present work, eleven chlorogenic acid amides have been synthesized and evaluated for their antioxidant properties (as DPPH and ORAC) and inhibition activity towards the two enzymes and, with the aim to obtain dual-action antidiabetic agents. The two most promising hypoglycemic compounds, bearing a tertiary amine function on an alkyl chain (8) and a benzothiazole scaffold (11), showed IC 50 values lower than that of (1) (45.5 µM α-Glu; 105.2 µM α-Amy). Amides 8 and 11 were by far more potent α-Glu inhibitors than the antidiabetic drug acarbose (IC 50  = 268.4 µM) and about twice less active toward α-Amy than acarbose (IC 50  = 34.4 µM). Kinetics experiments on amides 8 and 11 indicated these compounds as mixed-type inhibitors of α-Glu with K' i values of 13.3 and 6.3 µM, respectively. The amylase inhibition occurred with a competitive mechanism in the presence of 8 (K i  = 79.7 µM) and with a mixed-type mechanism with 11 (K i  = 19.1 µM; K' i  = 93.6 µM). Molecular docking analyses supported these results, highlighting the presence of additional binding sites in both enzymes. Fluorescence experiments confirmed the grater affinity of amides 8 and 11 towards the two enzymes respect to (1). Moreover, a significant enhancement in acarbose efficacy was observed when inhibition assays were performed adding acarbose and amide 11. The above outcomes pinpointed the benzothiazole-based amide 11 as a promising candidate for further studies on type 2 diabetes treatment, both alone or combined with acarbose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The fruit of Citrus medica L. var. sarcodactylis Swingle is not only used as a traditional medicinal plant, but also served as a delicious food. Six new (3'→7″)-biflavonoids (1-6), and twelve known biflavonoid derivatives (7-18) were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. Their structures were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, and IR spectral data coupled with the data described in the literature. Compounds (1-18) were evaluated for their hypolipidemic activities with Orlistat as the positive control, and assayed for their immunosuppressive activities with Dexamethasone as the positive control, respectively. Among them, compounds (1-3) exhibited moderate inhibition of pancreatic lipase activity by inhibiting 68.56 ± 1.40%, 56.18 ± 1.57%, 53.51 ± 1.59% of pancreatic lipase activities at the concentration of 100 μM, respectively. Compounds (4-6) and 8 showed potent immunosuppressive activities with the IC 50 values from 16.83 ± 1.32 to 50.90 ± 1.79 μM. The plausible biogenetic pathway and preliminary structure activity relationship of the selected compounds were scientifically summarized and discussed in this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: An algorithm was designed aiming to provide consistency of pancreatic enzyme replacement therapy (PERT) dosing/titration across healthcare professionals in pancreaticobiliary cancers (PBCs). This prospective observational study aimed to validate this algorithm., Methods: Consecutive patients with inoperable or postoperative PBC with pancreatic exocrine insufficiency (PEI) symptoms, not taking PERT, or taking below the algorithm "starting dose," were eligible. A dietitian or clinical nurse specialist reviewed patients for up to 3 weeks, titrating PERT as per the algorithm. Feasibility of algorithm deliverability was assessed by the percentage of patients with successful completion (primary objective)., Results: Twenty-five patients were eligible (N = 25): at baseline, 22 took PERT (100% on suboptimal doses, 54.5% taking incorrectly) and 3 initiated PERT because of PEI symptoms. Algorithm completion (20 of 25, 80%) confirming deliverability by dietitians (11 of 12, 92%) and clinical nurse specialists (9 of 13, 69%). Symptom resolution occurred in 8 of 19 (42%), 3 of 7 (43%), and 1 of 3 (33%) patients at first, second, and third reviews, respectively; advice compliance was between 63% and 86%., Conclusions: This algorithm provides a structured method to titrate PERT. At diagnosis, all patients with PBC should be assessed for PEI and adequate PERT initiated. Regular reviews are required for timely symptom resolution and adequate escalation, facilitating differential diagnosis if refractory symptoms exist., Competing Interests: L.E.C. was funded by Pancreatic Cancer UK Fellowship (Clinical Pioneer Award 2015) and a grant from the NET patient foundation. L.E.C., M.A., and A.L. received an education and travel grant received from Mylan. M.G.M. received speaker honoraria from Mylan. A.L.’s salary was in part funded by The Christie Charity. The other authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

(-)-Epigallocatechin gallate (EGCG), the chief dietary constituent in green tea ( Camellia sinensis ), is relatively unstable under oxidative conditions. This study evaluated the use of non-thermal dielectric barrier discharge (DBD) plasma to improve the anti-digestive enzyme capacities of EGCG oxidation products. Pure EGCG was dissolved in an aqueous solution and irradiated with DBD plasma for 20, 40, and 60 min. The reactant, irradiated for 60 min, exhibited improved inhibitory properties against α-glucosidase and α-amylase compared with the parent EGCG. The chemical structures of these oxidation products 1 - 3 from the EGCG, irradiated with the plasma for 60 min, were characterized using spectroscopic methods. Among the oxidation products, EGCG quinone dimer A ( 1 ) showed the most potent inhibitory effects toward α-glucosidase and α-amylase with IC 50 values of 15.9 ± 0.3 and 18.7 ± 0.3 μM, respectively. These values were significantly higher than that of the positive control, acarbose. Compound 1 , which was the most active, was the most abundant in the plasma-irradiated reactant for 60 min according to quantitative high-performance liquid chromatography analysis. These results suggest that the increased biological capacity of EGCG can be attributed to the structural changes to EGCG in H 2 O, induced by cold plasma irradiation.

Background: Patients with cystic fibrosis (CF) and pancreatic insufficiency need pancreatic enzyme replacement therapy (PERT) for dietary lipids digestion. There is limited evidence for recommending the adequate PERT dose for every meal, and controlling steatorrhea remains a challenge. This study aimed to evaluate a new PERT dosing method supported by a self-management mobile-app., Methods: Children with CF recruited from 6 European centres were instructed to use the app, including an algorithm for optimal PERT dosing based on in vitro digestion studies for every type of food. At baseline, a 24h self-selected diet was registered in the app, and usual PERT doses were taken by the patient. After 1 month, the same diet was followed, but PERT doses were indicated by the app. Change in faecal fat and coefficient of fat absorption (CFA) were determined., Results: 58 patients (median age 8.1 years) participated. Baseline fat absorption was high: median CFA 96.9%, median 2.4g faecal fat). After intervention CFA did not significantly change, but range of PERT doses was reduced: interquartile ranges narrowing from 1447-3070 at baseline to 1783-2495 LU/g fat when using the app. Patients with a low baseline fat absorption (CFA<90%, n=12) experienced significant improvement in CFA after adhering to the recommended PERT dose (from 86.3 to 94.0%, p=0.031)., Conclusion: the use of a novel evidence-based PERT dosing method, based on in vitro fat digestion studies incorporating food characteristics, was effective in increasing CFA in patients with poor baseline fat absorption and could safely be implemented in clinical practice., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: To explore the effective and safe medicines for treating diabetes., Methods: Hydroalcoholic extracts of 130 medicinal plants belonging to 66 families were evaluated using porcine pancreatic lipase (PPL) inhibition and glucose uptake methods together with a literature review., Results: The extracts of 22 species showed the PPL inhibition activity; 18 extracts of 15 species stimulated glucose uptake in 3T3-L1 adipocytes. Among them, Mansonia gagei J.R. Drumm., Mesua ferrea L., and Centella asiatica (L.) Urb. exhibited both activities. The extracts of Caladium lindenii (André) Madison rhizomes and Azadirachta indica A. Juss. leaves presented the utmost lipase inhibitory activity with IC 50 of 6.86 ± 0.25 and 11.46 ± 0.06  μ g/mL, respectively. The extracts of Coptis teeta Wall. rhizomes and Croton tiglium L. seeds stimulated the maximum glucose uptake. Ten species are reported to have antidiabetic activity for the first time. Flavonoids and triterpenoids are the dominant antidiabetic compounds in selected medicinal plants from Myanmar., Conclusions: P. zeylanica , L. cubeba, H. crenulate , M. gagei , C. teeta , and M. ferrea are worthy to advance further study according to their strong antidiabetic activities and limited research on effects in in vivo animal studies, unclear chemical constitutes, and safety., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Dongdong Zhang et al.)

Young barley leaves (Hordeum vulgare L.) have various health effects and are employed as an ingredient in the production of health-promoting foods. Promoting antiobesity is one such health effect; however, the mechanism and bioactive compounds are unclear. In this research, young barley leaf extract (YB) was demonstrated to possess pancreatic lipase inhibitory activity. The addition of YB to a high-fat diet in mice increased fecal lipid content, indicating reduced absorption of lipids as the mechanism underlying antiobesity effect. The investigation of bioactive compounds in YB resulted in the identification of fructose-bisphosphate aldolase as a proteinous lipase inhibitor. Maximum inhibition of the protein was 45%, but inhibition was displayed at a concentration as low as 16 ng/mL, which is a characteristic inhibition compared with other reported proteinous lipase inhibitors., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

The present paper reports the determination of the activation energies and the optimum temperatures of starch hydrolysis by porcine pancreas α -amylase. The parameters were estimated based on the literature data on the activity curves versus temperature for starch hydrolysis by α-amylase from porcine pancreas. It was assumed that both the hydrolysis reaction process and the deactivation process of α -amylase were first-order reactions by the enzyme concentration. A mathematical model describing the effect of temperature on porcine pancreas α -amylase activity was used. The determine deactivation energies E a were from 19.82 ± 7.22 kJ/mol to 128.80 ± 9.27 kJ/mol, the obtained optimum temperatures T opt were in the range from 311.06 ± 1.10 K to 326.52 ± 1.75 K. In turn, the values of deactivation energies E d has been noted in the range from 123.57 ± 14.17 kJ/mol to 209.37 ± 5.17 kJ/mol. The present study is related to the starch hydrolysis by α -amylase. In the industry, the obtained results the values E a , E d , T opt can be used to design and optimize starch hydrolysis by α -amylase porcine pancreas. The obtained results might also find application in research on the pharmaceutical preparations used to treat pancreatic insufficiency or prognosis of pancreatic cancer.

The present study was aimed to evaluate the functional efficacy of plant extracts as a source of pancreatic lipase inhibitor and antioxidant in goat meat nuggets to address the fat paradox issue of red meat. The PPLIA, antioxidant potential, and resistance against fat digestion were in the order ofPhyllanthus emblica > Eucalyptus globulus > Tinospora cordifolia.PPL inhibition activities of water and ethanolic extracts fromPhyllanthus emblicausing DNPB and Triolein as substrate were 63.76, 67.94 and 56.17 and 64.36 percent respectively whereas, TPC, DPPH RSA, FRPA were 40.82 and 59.52 (mgGAE/g), 54.89 and 59.84 (percent), 1.26 and 1.61 (OD) respectively. The average diameter of fat globules in digest was maximum (8.91 µm) withPhyllanthus emblicafruits extracts whereas; TBARs (0.347 mg MDA/Kg) and FFA (4.47 µg/g) values were lowest. This study showed that extracts from plants can act as a promising natural alternative in the development of healthy meat products., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nigella sativa (NS) is a well-known plant for its various benefits and multiuse in traditional medicine. This study is aimed at investigating the chemical composition of the different NS fractions by using GC-MS for the esterified fatty acids or HPLC-UV for organic fraction and at evaluating the inhibitory effect on pancreatic α -amylase ( in vitro , in vivo ) and intestinal glucose absorption. Among all the investigated fractions, it was shown that they are rich with different molecules of great interest. The n-hexane fraction was characterized by the presence of linoleic acid (44.65%), palmitic acid (16.32%), stearic acid (14.60%), and thymoquinone (8.7%), while among the identified peaks in EtOH fraction we found catechin (89.03 mg/100 g DW), rutin (6.46 mg/100 g DW), and kaempferol (0.032 mg/100 g DW). The MeOH fraction was distinguished with the presence of gallic acid (19.91 mg/100 g DW), catechin (13.79 mg/100 g DW), and rutin (21.07 mg/100 g DW). Finally, the aqueous fraction was marked by the existence of different molecules; among them, we mention salicylic acid (32.26 mg/100 g DW), rutin (21.46 mg/100 g DW), and vanillic acid (3.81 mg/100 g DW). Concerning the inhibitory effect on pancreatic α -amylase, it was found that in the in vitro study, the best IC 50 registered were those of EtOH (0.25 mg/ml), MeOH (0.10 mg/ml), aqueous (0.031 mg/ml), and n-hexane fraction (0.76 mg/ml), while in the in vivo study an important inhibition of α -amylase in normal and diabetic rats was observed. Finally, the percentage of intestinal glucose absorption was evaluated for all tested extracts and it was ranging from 24.82 to 60.12%. The results of the present study showed that the NS seed fractions exert an interesting inhibitory effect of α -amylase and intestinal glucose absorption activity which could be associated with the existent bioactive compounds. Indeed, these compounds can be used as antidiabetic agents because of their nontoxic effect and high efficacy., Competing Interests: The authors of this work declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Mohammed Dalli et al.)

Acinar cell injury and the inflammatory response are critical bioprocesses of acute pancreatitis (AP). We investigated the role and underlying mechanism of sulfiredoxin-1 (Srxn1) in AP. Mild AP was induced by intraperitoneal injection of cerulein and severe AP was induced by partial duct ligation with cerulein stimulation or intraperitoneal injection of L-arginine in mice. Acinar cells, neutrophils, and macrophages were isolated. The pancreas was analyzed by histology, immunochemistry staining, and TUNEL assays, and the expression of certain proteins and RNAs, cytokine levels, trypsin activity, and reactive oxygen species (ROS) levels were determined. Srxn1 was inhibited by J14 or silenced by siRNA, and overexpression was introduced by a lentiviral vector. Transcriptomic analysis was used to explore the mechanism of Srxn1-mediated effects. We also evaluated the effect of adeno-associated virus (AAV)-mediated overexpression of Srxn1 by intraductal administration and the protection of AP. We found that Srxn1 expression was upregulated in mild AP but decreased in severe AP. Inhibition of Srxn1 increased ROS, histological score, the release of trypsin, and inflammatory responses in mice. Inhibition of Srxn1 expression promoted the production of ROS and induced apoptosis, while overexpression of Srxn1 led to the opposite results in acinar cells. Furthermore, inhibition of Srxn1 expression promoted the inflammatory response by accumulating and activating M1 phenotype macrophages and neutrophils in AP. Mechanistically, ROS-induced ER stress and activation of Cathepsin B, which converts trypsinogen to trypsin, were responsible for the Srxn1 inhibition-mediated effects on AP. Importantly, we demonstrated that AAV-mediated overexpression of Srxn1 attenuated AP in mice. Taken together, these results showed that Srxn1 is a protective target for AP by attenuating acinar injury and inflammation through the ROS/ER stress/Cathepsin B axis.

Acute pancreatitis (AP) is an inflammatory reaction of pancreatic tissue self-digestion, edema, hemorrhage, and even necrosis after the activation of pancreatic enzymes in the pancreas caused by a variety of etiologies. This study was aimed to explore the functions and mechanism of Wip1 in AP. Twenty male SD rats were randomly assigned into 2 groups (control group: saline treatment; AP group: cerulein treatment). And cerulein-treated AR42J cells were conducted as AP model in vitro. The levels of amylase were detected by using the Beckman biochemical analyzer. The levels of IFNβ and TNFα were analyzed by ELISA. The autophagosomes were observed by transmission electron microscopy. The Wip1-specific shRNAs were transfected to AR42J cells to silence the expression of Wip1. The levels of Wip1 were measured by qRT-PCR and Western blot. The levels of STING/TBK1/IRF3 and LC3 were measured by Western blot. The AP model was successfully constructed by cerulein administration. Wip1 was notably upregulated in AP models. Autophagy and STING pathway activation were involved in the development of AP. Wip1 inhibition counteracts the promotion effect on inflammatory response induced by cerulein in AR42J Cells. Wip1 inhibition inhibited the activity of the STING/TBK1/IRF3 and reduced LC3 levels in AP. This study preliminarily explored that Wip1 could regulate autophagy and participate in the development of AP through the STING/TBK1/IRF3 signaling pathway.

Pancreatic lipase (PL), a key target for the prevention and treatment of obesity, plays crucial roles in the hydrolysis and absorption of in dietary fat. In this study, a series of pyrazolones was synthesized, and their inhibitory effects against PL were assayed by using 4-methylumbelliferyl oleate (4-MUO) as optical substrate for PL. Comprehensive structure-activity relationship analysis of these pyrazolones led us to design and synthesize a novel compound P32 (5-(naphthalen-2-yl)-2-phenyl-4-(thiophen-2-ylmethyl)-2,4-dihydro-3H-pyrazol-3-one) as a potent mixed-competitive inhibitor of PL (IC 50 =0.30 μM). In addition, P32 displayed some selectivity over other known serine hydrolases. A molecular docking study for P32 demonstrated that the inhibitory activity of P32 towards PL could be attributed to the π-π interactions of 2-naphthyl unit (R 1 ) and hydrophobic interactions of phenyl moiety (R 3 ) with the active site of PL. Thus, P32 could serve as promising lead compound for the development of more efficacious and selective pyrazolones-type PL inhibitors for biomedical applications., (© 2021 Wiley-VCH GmbH.)