Inhibition Of Pancreatic Lipase Research Articles

Synthesis, Biological Activity and Molecular Docking Studies of Novel Sulfonate Derivatives Bearing Salicylaldehyde.

Enzyme activity alterations have been associated with many metabolism disorders and have crucial roles in the pathogenesis of some diseases. Tyrosinase is a key enzyme in melanin biosynthesis, which is responsible for skin pigmentation to protect the skin from solar radiation. Pancreatic lipase has been considered a key enzyme for the treatment of obesity. Herein, we reported the synthesis and enzyme inhibitions of a series of sulfonates as possible tyrosinase and pancreatic lipase inhibitors. According to the calculated IC50 values, compound 3f (74.1±11.1 μM) and compound 3c (86.6±6.9 μM) were determined to be the best inhibitors among the synthesized compounds for the tyrosinase and pancreatic lipase enzymes, respectively. The approach yielded at extremely high level by creating very flexible structural domains for the chemically modified groups. The structural characterization of the target molecules was implemented by 1 H-NMR, 13 C-NMR, and HR-MS analyses. Also, molecular docking studies of the synthesized compounds with tyrosinase and pancreatic lipase enzymes were conducted using AutoDock Vina software. Additionally, the studies of the absorption distribution, metabolism, and excretion (ADME) were performed to uncover the target compounds' pharmacokinetics, drug similarities, and medicinal properties of the novel sulfonate derivatives bearing salicylaldehyde.

Senyawa Fucodiphlorethol Dan Phloroglucinol Alga Coklat Sebagai Inhibitor Lipase Secara In Silico

<p class="E-JOURNALAbstractBodyEnglish">Brown algae is a marine functional food that high fibers, vitamins, and bioactive compounds. Brown algae improved blood glucose and lipid profile. This study investigated the potential activity of two bioactive compounds from brown algae, as anti-obesity through pancreatic lipase inhibition. Molecular docking was conducted for investigating the lipase inhibition of bioactive compounds. Lipase structure (PDB ID 1ETH) was obtained from protein data bank and docked with fucodiphlorethol and phloroglucinol in specific position. Then, the complex was analyzed by PyMol following by Discovery Studio version 21.1.1. Phloroglucinol - pancreatic lipase showed five amino acid residues by hydrogen bonds, hydrophobic and electrostatic. Fucodiphlorethol - pancreatic lipase generated binding energy -392 kJ/mol and consisted of eight hydrogen bonds, three electrostatic, and 4 hydrophobic interactions. The active sites of fucodiphlorethol and phloroglucinol with lipase were not considered as active sites or catalytic sites. Therefore, we predicted that both of fucodiphlorethol and phloroglucinol inhibit lipase allosterically by altering the protein structure conformations. molecular docking analysis suggested that fucodiphlorethol and phloroglucinol have potential antiobesity effect by inhibiting lipase. Molecular dynamic are needed for further investigation.</p>

Pd(II)-Schiff base complexes: Synthesis, characterization, Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions, enzyme inhibition and antioxidant activities

In this study, new coordination complexes (1a-1e) of Pd(II) with Schiff base ligands were synthesized and characterized by elemental analysis, magnetic susceptibility, molar conductivity, FT-IR, 1H–13C NMR spectroscopy, UV–vis spectroscopy, and mass spectrometry techniques. The ligands formed only 1:2 complexes with the Pd(II) except for the complex 1e. The thermal analysis of the complexes was performed by the TGA technique. The antioxidant potential, enzyme inhibition activity, and catalytic properties of the complexes were investigated as well. The Pd(II) complexes 1b and 1c indicated the best catalytic activity with 62.63% and 61.05% selectivity in the conversions of 82.61% and 87.84%. The in vitro antioxidant activity showed that the Pd(II) complexes, particularly 1a and 1e have effective antioxidant activities. According to the enzyme activity analyses, complex 1b (IC50 value 69.3 ± 5.2 μM) showed the most effective pancreatic lipase inhibition, whereas complex 1e (IC50 value 25.7 ± 3.2 μM) had the most effective tyrosinase inhibition among the synthesized compounds. Overall, the present paper discusses the synthesis, characterization and catalytic activities of various novel Pd(II)-Schiff base complexes with their antioxidant potentials, pancreatic lipase and tyrosinase inhibitory activities.

Synthesis, characterization, and enzyme inhibition activities of 4-(methylthio)-N-propylaniline-phenylpiperazine and sulfonamide derivatives

We have combined piperazine, thioether, and sulfonamide structural motifs in a mainframe for biological evaluation. The synthesis involved the alkylation of 4-aminothioanisole with chloroalkyl piperazine followed by treatment of resulting amino piperazine 3 with various aryl sulfonyl chlorides. All target compounds (3–7) were characterized by 1H, 13C, HRMS, and IR. In addition, all obtained piperazine derivatives were evaluated for their tyrosinase and pancreatic lipase enzyme inhibitory activities. The enzyme analyses showed that some of the piperazine derivatives possess effective tyrosinase inhibitions with IC50 values of 18.7 ± 1.8 for compound 6 and 24.7 ± 3.4 for compound 4, which is close to the IC50 value of kojic acid (19.2 ± 1.2 µM). On the other hand, the synthesized compounds showed low IC50 values in the range from 46.2 ± 4.9 to 86.6 ± 8.4 µM against pancreatic lipase enzyme. Compound 3 was found to be the most effective pancreatic lipase inhibitor among the synthesized compounds. The IC50 value of compound 3 (46.2 ± 4.9 µM) was determined slightly lower than the IC50 value of orlistat (49.5 ± 3.2 µM), pointing to more effective inhibition. Finally, in silico molecular docking interactions of piperazine derivatives were evaluated for their tyrosinase and pancreatic lipase enzyme inhibitory activities using Chimera molecular visualization and AutoDock Vina software.

Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation, chemical profiling and biochemical assay

Although herbal medicines (HMs) are widely used in the prevention and treatment of obesity and obesity-associated disorders, the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood. Recently, we assessed the inhibitory potentials of several HMs against human pancreatic lipase (hPL, a key therapeutic target for human obesity), among which the root-extract of Rhodiola crenulata (ERC) showed the most potent anti-hPL activity. In this study, we adopted an integrated strategy, involving bioactivity-guided fractionation techniques, chemical profiling, and biochemical assays, to identify the key anti-hPL constituents in ERC. Nine ERC fractions (retention time = 12.5–35 min), obtained using reverse-phase liquid chromatography, showed strong anti-hPL activity, while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS/MS). Among the identified ERC constituents, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (PGG) and catechin gallate (CG) showed the most potent anti-hPL activity, with pIC50 values of 7.59 ± 0.03 and 7.68 ± 0.23, respectively. Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner, with inhibition constant (Ki) values of 0.012 and 0.082 μM, respectively. Collectively, our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC, as well as to elucidate their anti-hPL mechanisms. These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

Characterization, Antioxidant Activities, and Pancreatic Lipase Inhibitory Effect of Extract From the Edible Insect Polyrhachis vicina.

Oxidative stress and obesity are critical risk factors for metabolic syndrome. The consumption of functional food ingredients can a viable strategy to alleviate oxidative stress and obesity. In this study, the hydro-ethanolic extract of the edible insect Polyrhachis vicina was prepared and its bioactive components were characterized. The total polyphenol contents, total flavonoid contents, antioxidant and pancreatic lipase (PL) inhibitory activities of the extract were determined in vitro. In total, 60 bioactive components were tentatively identified in the P. vicina extract. Polyphenols and fatty acids were further quantified using LC-MS and GC-MS, respectively. P. vicina extract possessed excellent antioxidant and PL inhibition activities. Salicylic acid, gallic acid, liquiritigenin, and naringenin, which were the major polyphenols in the P. vicina extract, interacted with PL through hydrogen bonding, hydrophilic or hydrophobic and pi-cation interactions. Thus, P. vicina extract can be used as a nutraceutical to alleviate oxidative stress-induced disease and manage obesity.

Evaluation of in vitro lipid-lowering properties of ‘Saba’ banana [Musa acuminata x balbisiana (BBB group) ‘Saba’] peel pectin from different extraction methods

Introduction: This study was conducted to investigate the in-vitro lipid-lowering properties of ‘Saba’ banana peel pectin (SBP) extracted using three methods for its possible use as a dietary fibre ingredient. Methods: Pectin from ‘Saba’ banana peels were extracted using acid extraction (citric acid), enzymatic extraction (cellulase), and microwave-assisted extraction. In-vitro lipid-lowering assays were performed using spectrophotometry for pancreatic lipase inhibition and cholesterol binding, while liquid chromatography was used for bile acid-binding capacity. Results: Results revealed that all SBPs were not able to inhibit pancreatic lipase activity. However, all SBPs can notably bind to cholesterol and bile acids, taurocholate, and glycocholate. Acid-extracted pectin had the highest binding capacity to cholesterol (51.36%–55.07%) and glycocholate (27.37%), whereas all SBPs were similarly bound to taurocholate. Conclusion: The results of this study showed that acidextracted SBPs can significantly bind to cholesterol and bile acids, glycocholate and taurocholate, thereby indicating a possible reduction in lipid metabolism.

Discovery of Novel Epoxyketone Peptides as Lipase Inhibitors.

Obesity is the most common nutritional disorder in the developed world and is associated with important comorbidities. Pancreatic lipase (PL) inhibitors play a key role in the metabolism of human fat. A series of novel epoxyketones peptide derivatives were investigated for their pancreatic lipase inhibitory activity. The epoxyketone moiety is a well-known reactive electrophile group that has been used as part of proteasome inhibitors in cancer therapy, and it is widely believed that these are very selective for targeting the proteasome active site. Here we investigated various peptide derivatives with an epoxide warhead for their anti-lipase activity. The assessment of these novel epoxyketones was performed by an in-house method that we developed for rapid screening and identification of lipase inhibitors using GC-FID. Herein, we present a novel anti-lipase pharmacophore based on epoxyketone peptide derivatives that showed potent anti-lipase activity. Many of these derivatives had comparable or more potent activity than the clinically used lipase inhibitors such as orlistat. In addition, the lipase appears to be inhibited by a wide range of epoxyketone analogues regardless of the configuration of the epoxide in the epoxyketone moiety. The presented data in this study shows the first example of the use of epoxyketone peptides as novel lipase inhibitors.

UPLC/ESI-Q-TOF-MS analysis of (poly)phenols, tocols and amino acids in Chaenomeles leaves versus in vitro anti-enzyme activities

The aim of this study was to investigate the content of phenolics, free amino acids, tocopherols, tocotrienols and in vitro biological activities (α-amylase, α-glucosidase, and pancreatic lipase inhibition activity) of 12 cultivars of Chaenomeles × superba, japonica and speciosa leaves. In the present work 39 phenolic compounds were tentatively identified, including polymeric procyanidins > flavan-3-ols > phenolic acids > flavonols > flavanones > flavones > ellagitannins. Chaenomeles leaves contained on average 16.8 g of phenolics per 100 g dry weight (dw), with C. × superba ˈNicolineˈ displaying the highest (27.5 g/100 g dw), and C. × superba ˈColour Trailˈ the lowest (7.7 g/100 g dw) total phenolic content. Chaenomeles leaves possess all eight tocol analogs (four tocopherols (TP), and four tocotrienols (TT)), ranked in decreasing content: α-TP > β-TP > γ-TP > δ-TP > α-TT > β-TT > δ-TT > γ-TT. The most active form (α-tocopherol) was present in amounts from 480.6 to 7201.1 µg/100 g dw. 23 amino acids were identified, including all nine essential amino acids. The highest amount of O-phospho-L-serine was found (average 249.2 mg/100 g dw). Leaves of C. japonica ˈRed Joyˈ displayed the highest total amino acid content (2735.2 mg/100 g dw). Chaenomeles leaves showed α-amylase (8.2–24.5 mg/mL), α-glucosidase (1.2-6.3 mg/mL), and pancreatic lipase (7.0-10.5 mg/mL) inhibition activity (expressed as half maximal inhibitory concentration, IC50). Chaenomeles leaves can be a good material for obtaining extracts rich in phenolics, vitamin E or amino acids, providing an alternative, natural source of these compounds to help meet the growing demand for nutraceuticals and supplements.

An in vitro and in silico study on the synthesis and characterization of novel bis(sulfonate) derivatives as tyrosinase and pancreatic lipase inhibitors

Herein, we present a straightforward synthetic strategy mediated by triethylamine to prepare the target salicylaldehyde functional group's bearing bis(sulfonate) derivatives. The novel bis(sulfonate) derivatives (compounds 2a–i) were designed, synthesized, and characterized for the first time. The structures of compounds were determined by 1H NMR, 13C NMR, and HRMS techniques. Enzyme inhibition effects and enzyme interactions of compounds were evaluated on tyrosinase and pancreatic lipase enzymes by using in silico and in vitro methods. According to the enzyme assays, compound 2h had more effective inhibition against the pancreatic lipase enzyme with a lower IC50 value (53.3 ± 2.7 µM) than the other compounds. On the other hand, two of the newly synthesized compounds (2f and 2h) had effective inhibitions against the tyrosinase enzyme with having (49.5 ± 2.5 µM) IC50 values. In addition, molecular docking studies were performed to determine the interactions and binding energy levels of the bis(sulfonate) derivatives with tyrosinase and pancreatic lipase. Also, additional ADME studies of the bis(sulfonate) compounds were evaluated.

Theophylline Extracted from Fu Brick Tea Affects the Metabolism of Preadipocytes and Body Fat in Mice as a Pancreatic Lipase Inhibitor.

The dramatic increase in obesity is putting people under increasing pressure. Lipase inhibitors, as a kind of effective anti-obesity drug, have attracted more and more researchers’ attention in recent years because of their advantages of acting on the intestinal tract and having no side effects on the central nervous system. In this study, lipase inhibitor Fu Brick Theophylline (FBT) was screened based on enzyme molecular dynamics, and the inhibition mechanism of lipase inhibitors on obesity was analyzed and discussed at the cellular level and animal model level. We found that FBT had high inhibition effects of lipase with an IC50 of 1.02~0.03 μg/mL. Firstly, the laboratory used 3T3-L1 proadipocytes as models, flow cytometry was used to detect the effects of FBT on the cycle, apoptosis and intracellular ROS activity of proadipocytes. To study the contents of triglyceride, total cholesterol, related metabolites and related gene and protein expression in adipocytes. The results showed that FBT could reduce ROS production and inflammatory factor mRNA expression during cell differentiation. Secondly, by establishing the animal model of high-fat feed ob nutritional obese mice, the morphological observation and gene expression analysis of body weight, fat rate, adipocyte and hepatocyte metabolism of FBT obese mice were further discussed. It was proven that FBT can effectively reduce the degree of fatty liver, prevent liver fibrosis and fat accumulation, and improve the damage of mitochondrial membrane structure. This study provides a theoretical basis for the screening and clinical treatment of lipase inhibitors.

Discovery and Characterization of the Naturally Occurring Inhibitors Against Human Pancreatic Lipase in Ampelopsis grossedentata.

Pancreatic lipase (PL) inhibitor therapy has been validated as an efficacious way for preventing and treating obesity and overweight. In the past few decades, porcine PL (pPL) is widely used as the enzyme source for screening the PL inhibitors, which generates a wide range of pPL inhibitors. By contrast, the efficacious inhibitors against human PL (hPL) are rarely reported. This study aims to discover the naturally occurring hPL inhibitors from edible herbal medicines (HMs) and to characterize the inhibitory mechanisms of the newly identified hPL inhibitors. Following the screening of the inhibition potentials of more than 100 HMs against hPL, Ampelopsis grossedentata extract (AGE) displayed the most potent hPL inhibition activity. After that, the major constituents in AGE were identified and purified, while their anti-hPL effects were assayed in vitro. The results clearly showed that two abundant constituents in AGE (dihydromyricetin and iso-dihydromyricetin) were moderate hPL inhibitors, while myricetin and quercetin were strong hPL inhibitors [half-maximal inhibitory concentration (IC50) values were around 1.5 μM]. Inhibition kinetic analyses demonstrated that myricetin and quercetin potently inhibited hPL-catalyzed near-infrared fluorogenic substrate of human pancreatic lipase (DDAO-ol) hydrolysis in a non-competitive inhibition manner, with Ki values of 2.04 and 2.33 μM, respectively. Molecular dynamics simulations indicated that myricetin and quercetin could stably bind on an allosteric site of hPL. Collectively, this study reveals the key anti-obesity constituents in AGE and elucidates their inhibitory mechanisms against hPL, which offers convincing evidence to support the anti-obesity and lipid-lowering effects of this edible herb.

The Effect of Orlistat on Sterol Metabolism in Obese Patients.

BackgroundOrlistat, a reversible inhibitor of pancreatic and gastric lipase, is known to have anti-obesity and antioxidant properties. Cholesterol intermediates and metabolites have diverse and important functions in cardiovascular disease. Therefore, we aimed to evaluate the effect of orlistat on sterol metabolism in overweight and obese adults after weight loss during the intervention or weight loss at 12 weeks.MethodsA total of 51 (27 in the control group and 24 in the experimental group), patients with a BMI of 27 or greater were randomly assigned in a 1:1 ratio to receive either orlistat (120 mg) three times a day plus phentermine hydrochloride (37.5 mg) once daily or a placebo three times a day plus phentermine hydrochloride (37.5 mg) once daily. The primary study outcome was sterol metabolism.ResultsThe experimental group exhibited significantly decreased metabolic signatures of serum sterols, free cholesterol, sitosterol, 7α-hydroxycholesterol (7α-OHC), and 7β-OHC at 12 weeks. The experimental group also exhibited significantly decreased metabolic ratios of sitosterol and 7α-OHC to cholesterol at 12 weeks. Regarding changes in sterol signatures from baseline to 6-month follow-up, free cholesterol, plant sterols, and cholesterol precursors tended to decrease with weight loss during the intervention and increase again as the weight was regained in both groups.ConclusionOrlistat treatment improves oxysterol metabolism in overweight and obese adults. Our findings support that orlistat plays a crucial role in the process of endothelial dysfunction and atherosclerosis via oxysterol modulation.

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 24h. After 24h 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 24h had the highest inhibitory activity of lipase (p<0.05). CSC/collagenase hydrolysates (10mg/mL) presented the highest inhibitory activity (75.53%) (p<0.05). Ultrafiltrated fractions >5kDa from CSC/collagenase and PSC/MPRO NX® hydrolysates were the most bioactive fractions (IC50: 4.33mg/mL). The highest were obtained by CSC peptides (IC50s: 6.30 and 6.08mg/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.

In Vitro Antilipidic and Antithrombotic Activities of Plectranthus glandulosus (Lamiaceae) Leaves Extracts and Fractions.

Objective The present study investigated the effect of the leaves extracts and fractions of Plectranthus glandulosus on the inhibition of pancreatic lipase, cholesterol esterase, adipocytes lipid uptake, and antithrombotic activity which may be important in atherosclerosis development. Methods Aqueous, ethanolic, and hydroethanolic extracts of Plactranthus glandulosus were prepared by maceration. The hydroethanolic extract was fractionated into n-hexane, ethylacetate, and n-butanol fractions and their inhibition of pancreatic lipase, cholesterol esterase, adipocytes lipid uptake, and antithrombotic activities measured. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis was carried out to determine phytochemical constituents present in the extracts. Results The standard orlistat exhibited a higher inhibitory activity on pancreatic lipase and cholesterol esterase (16.31 μg/mL and 15.75 μg/mL, respectively) compared to ethyl acetate fraction (IC50, 17.70 μg/mL and IC50, 24.8 μg/mL, respectively). Among crude extract, hydroethanolic extract showed a better inhibition against pancreatic lipase (IC50, 21.06 μg/mL) and cholesterol esterase (IC50, 25.14 μg/mL) though not comparable to the effect of orlistat. The best lipid uptake inhibition was observed in the hydroethanolic extract (IC50, 45.42 μg/mL) followed by the ethyl acetate fraction (IC50, 47.77 μg/mL). A better antithrombolytic activity was exhibited by the ethyl acetate fraction at all concentrations (50-800 μ/mL), while hydroethanolic extract exhibited the best activity among crude extract. However, these were not comparable to the standard aspirin. The LC-HRMS analysis revealed the presence of 7-O-methyl luteolin 5-O-β-D-glucopyranoside, chrysoeriol 5-O-β-D-glucopyranoside, 5,7-dihydroxy-3,2′,4′-trimethoxyflavone, and plectranmicin as major compounds in both hydroethanolic extract and ethyl acetate fraction. Conclusion Thus, our finding supports the traditional use of this plant, which might provide a potential source for future antiatherosclerotic drug discovery.

Spray dried extract of Callophyllum brasiliense Cambés produces a potent hypoglycemic effect and improves total serum cholesterol and triglycerides in diabetic rats

The species Calophyllum brasiliense Cambés (Calophyllaceae) is widespread throughout Central and South America. The stem bark infusion is used for lowering blood glucose. Aim: To optimize the spray dry extract of this plant using a D-optimal experimental design. Materials and methods: As factors were used the air-drying speed (3.5-4.5 m3/h), the feed flow rate of the suspension (5-11 mL/min), and the inlet air temperature (90-130 °C). The dried extract was character-ized by measuring the phenolics and flavonoids content, moisture, the water activity, apparent densities, flowability, and compressibility. The antioxidant activity, the inhibitory activity of lipase and alpha-glycosidase, and the antiglycant activity of the spray dried extract (SDE) were evaluated. Subsequently, the hypoglycemic activity was evaluated in rats by monitoring the blood glucose level, triglycerides, and choles-terol. Results: Inlet air temperature and feed flow rate were the factors that most affected the yield and phenolic content. SDE showed a potent antioxidant effect (IC50 1.83 μg/mL), a potent α-glycosidase (IC50 74.45 μg/mL) and pancreatic lipase (IC50 27.33 μg/mL) inhibition. A potent antiglycation effect (IC50 9.45μg/mL) was also observed. Conclusion: the SDE showed a potent hypoglycemic effect at 100 mg/kg. These results suggest that SDE could activate four important pathways that can contribute to diabetes control.

Phytochemical and biological characterization of dry outer scales extract from Tropea red onion (Allium cepa L. var. Tropea)–A promising inhibitor of pancreatic lipase

BackgroundAllium cepa L. var. Tropea is typically cultivated in Calabria (Italy) and it is certified as “Cipolla Rossa di Tropea Calabria-PGI” (Tropea red onion). The use of clinically available anti-obesity drugs such as Orlistat is being gradually dismissed due to their side-effects and this has encouraged the search for alternative inhibitors of intestinal lipases such as phytochemicals showing less side-effects. In this study we aimed to evaluate for the first time the anti-obesity potential of the hydroalcoholic extract from the dry outer scales of Tropea red onion by the assesment of its capacity to inhibit pancreatic lipase. Its possible mechanism of action was also studied with planar lipid membranes (PLMs) surrogate of intestinal membranes. MethodsSpecialized metabolites in the extract were determined by GC–MS, HPLC-DAD, HPLC-UV-DAD and HPLC-HRMS analyses. Inhibition of pancreatic lipase was studied in vitro against crude lipase Type II from porcine pancreas. PLMs used in the electrophysiology measurements were made up of DOPS:DOPE:POPC. ResultsThe extract contained quercetin-4′-O-glucoside, quercetin and quercetin-3,4′-O-diglucoside as the most abundant phenolics. Among apolar constituents, γ-sitosterol, linoleic and stearic acids were dominant. The lipase inhibitory effect of the extract had an IC50 value equal to 0.77±0.03 mg/mL (positive control, IC50 = 0.018 mg/mL). The electrophysiological study demonstrated that the extract is able to incorporate into PLMs and to form transient channel-like events ConclusionsTaken altogether, the results allow us to suggest that the hydroalcoholic extract from the dry outer scales of Tropea red onion could prevent lipid ester hydrolysis and it has a protective effect against phospholipase as found for interfacially active compounds.

Discovery of triterpenoids as potent dual inhibitors of pancreatic lipase and human carboxylesterase 1

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 IC50 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 IC50 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.

Screening for pancreatic lipase inhibitors: evaluating assay conditions using p-nitrophenyl palmitate as substrate

Current in vitro pancreatic lipase inhibitor screenings are based on previous spectrophotometric lipase assays. Nevertheless, they are with little evaluation of assay conditions. This study focuses on the impacts of experimental factors on enzyme activity in the assay with p-nitrophenyl palmitate as substrate by monitoring their effects on the hydrolysis rates. On the results, experimental conditions for lipase inhibitory assay were proposed. Notably, 5 mM sodium deoxycholate as emulsifier not only maintains the assay homogeneity but also enhances lipase activity. Organic co-solvents to dissolve organic inhibitors including DMSO, EtOH, MeOH, IPA, AcCN [0–30% (v/v)] was found well tolerated by the enzyme. With 10% (v/v) glycerol, lipase solutions can be stored at –20°C for up to one month without significant loss of activity. The results reported here provide researchers the assay condition sets in which most inhibitors can be dissolved, and lipase activity is not severely affected. This could accelerate the rational development of novel lipase inhibitors.

Solvents effect on phenolics, iridoids, antioxidant activity, antibacterial activity, and pancreatic lipase inhibition activity of noni (Morinda citrifolia L.) fruit extract

This study focused on the relationship between content levels of phytochemicals and the biological activities of noni (Morinda Citrifolia L.) fruit extracts (NFEs) prepared with traditional solvents and deep eutectic solvents (DESs). The results indicated the total phenolic content in Bet-Gly (Betaine: Glycerol) extracts (11.89 mg GAE/g DW) and total iridoid content in 70% ethanol extracts (26.38 mg CE/g DW) were the highest. A total of 17 compounds were identified and quantified in NFEs. Traditional solvent extracts, except ethyl acetate, exhibited higher antioxidant activities than DESs. Three DES extracts showed higher activities against pancreatic lipase than traditional solvent extracts. Multivariate analysis revealed that the type of extraction solvent exerts a significant influence on the phytochemical compositions and biological activities of NFEs. This study provided valuable information on the efficient extraction of phytochemicals from noni fruits and DESs are promising green solvent for the extraction of bioactive compounds from noni fruits.