Lipase Inhibitory Activity Research Articles

Bacillus lipopeptides inhibit lipase activity and promote 3T3-L1 preadipocyte differentiation.

Bacillus lipopeptides have been reported to display anti-obesity effects. In the present study, Lipopeptides from Bacillus velezensis FJAT-45028 that consisted of iturin, fengycin and surfactin were reported. The lipopeptides exhibited a strong lipase inhibition activity in a concentration-dependent manner with a half maximal inhibitory concentration of 0.012 mg/mL, and the inhibition mechanism and type were reversible and competitive, respectively. Results of CCK8 assay showed that 3T3-L1 preadipocyte cells were completely viable under treatment of 0.050-0.2 mg/mL lipopeptides for 24 or 48 h. It was found that the lipopeptides could increase lipid droplets in the differentiated 3T3-L1 adipocytes in tested concentration and suppress the expression of peroxisome proliferator-activated receptor gamma (PPARγ). These results indicated the potential anti-obesity mechanism of the tested lipopeptides might be to inhibit lipase activity but not to suppress lipid accumulation in the adipocytes. Moreover, the lipopeptides could elevate glucose utilisation by 14.43%-33.81% in the differentiated 3T3-L1 adipocytes.

Structural characterization of noni (Morinda citrifolia L.) pectin and its inhibitory activity on pancreatic lipase

This study aimed to investigate the physicochemical properties and biological activities of noni pectin (NP) extracted using various solvents, three fractions of noni pectin were obtained using traditional chemical and deep eutectic solvents. NPs are composed of various ratios of galacturonic acid, arabinose, rhamnose, xylose, glucose, and galactose with different yields, molecular weights, esterification degrees (DE), and microstructures. Among the fractions, noni pectin extracted with Betaine-citric acid (BNP) exhibited higher molecular weight, degree for esterification and pancreatic lipase (PL) inhibitory activity than the other fractions. Enzyme kinetic analysis indicated that BNP inhibited PL via a noncompetitive mechanism. BNP significantly altered the secondary structure of PL and quenched PL fluorescence, suggesting a static quenching mechanism. Isothermal titration calorimetry (ITC) further demonstrated that the binding of BNP to PL was spontaneous and driven by enthalpy, primarily mediated by hydrogen bonding and van der Waals forces. Molecular docking simulations also confirmed strong noncovalent interactions (hydrogen bonding and van der Waals forces) between BNP and PL. This study validated the high efficiency of the deep eutectic solvent-extracted noni pectin fraction in pancreatic lipase inhibition.

Exploring flavonoid derivatives as potential pancreatic lipase inhibitors for obesity management: An in silico and in vitro study.

Obesity is widely recognized as a major public health issue and is one of the leading causes of death worldwide. Overweight and obesity are prominent lifestyle ailments that not only give rise to additional health issues but also play a role in the development of other chronic diseases, such as cancer, diabetes, metabolic syndrome, and cardiovascular diseases. Orlistat is now the only pharmaceutical drug for the management of obesity. However, prolonged use of orlistat has been associated with detrimental consequences, hence necessitating the development of a new drug with reduced or no adverse reactions. Pancreatic Lipase is a critical enzyme in lipid metabolism. Using naturally occurring compounds as PL inhibitors has garnered significant attention because of their diverse structure and low toxicity. The present work investigates the inhibitory action of flavonoids on PL using in silico and in vitro methods. Thirteen flavonoid derivatives and orlistat were docked with PL. The ADME properties of the flavonoid derivatives were studied, and most of the compounds are in admire range. The stability of the best-docked complexes was checked by REMD. The in silico study demonstrated favorable inhibitory activity of flavonoids compared to orlistat. Consequently, an enzyme inhibitory experiment was conducted to authenticate the in silico results. The lipase inhibitory activity was assessed by using p-nitrophenyl butyrate as the substrate. Kaempferol exhibited significant inhibitory activity against PL, as shown by its IC50 value of 72.7 ± 3µM. This study proposed a natural drug candidate with promising inhibitory efficacy against PL for obesity.

Effects of acid, alkaline and enzymatic extraction methods on functional, structural and antioxidant properties of dietary fiber fractions from quince (Cydonia oblonga Miller)

In this study, quince soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were obtained by acid extraction, enzyme extraction and alkaline extraction methods. The acid extracted DF displayed higher results compared to enzyme and alkaline extraction methods in terms of water holding capacity (15.97 g/g SDF), oil holding capacity (1.05 g/g SDF) and nitrite ion adsorption capacity (92.83 mg/g SDF). The antioxidant activity and phenolic content of acid extracted IDF were significantly higher than the other quince DFs. In addition, quince DFs exhibited in vitro hypoglycaemic activity, exhibiting high glucose adsorption capacity (237 mg/g) and α-amylase inhibition activity (82 %). Similarly, acid extracted SDF of quince showed in vitro hypolipidemic activity, with cholesterol adsorption capacity of 155 mg/g and lipase inhibition activity of 36 %. The structures and thermal properties of quince DFs were characterized by FT-IR and TGA. Quince DFs with high functional properties might be suitable agents for functional food formulations, such as meat products, low-calorie fruit bars, flour mixtures, etc.

Chemical composition and physiological bioactivities of Stiefia multicaulis (Vahl) Soják Vahl grown in Palestine

Background: Herbal products encompass a wide range of natural substances that show great potential as therapeutic materials. Consequently, there has been a substantial investigation into the therapeutic potential of numerous plant species in recent times. The present study sought to determine the components and assess the antioxidant, antilipase, α-amylase, and α-glycosidase enzyme inhibitory activities of Stiefia multicaulis (Vahl) Soják Vahl hexane, acetone, methanol, and aqueous fractions. Methods: Standard pharmacopeia methods were used to conduct screenings for both quantitative and qualitative phytoconstituents. The lipase, α-amylase, and α-glycosidase enzyme inhibitory activities were assessed using established reference methods. In addition, the antioxidant activity was assessed using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Results: The screening methods of pharmacopeias revealed that S. multicaulis contains a wide range of secondary metabolites, especially tannins. However, the most potent antioxidant, antilipase, α-glucosidase, and α-amylase inhibitory activities were acetone fraction, hexane, methanol, and aqueous S. multicaulis fractions, respectively. Conclusion: The current study outcomes are the first on the α-amylase, lipase, α-glucosidase inhibitory activities of S. multicaulis four solvent fractions. Further investigations are needed to assess the in vivo potential of these plant fractions in animal models.

Exploring the nutritional and biological properties of green coffee extracts: A comparative study of aqueous and enzymatic extraction processes

The effects of aqueous (AEP) and enzyme-assisted aqueous extraction processes (EAEP) on the biological and nutritional properties of green coffee extracts (protein and antioxidant-rich fraction) were investigated. All extracts exhibited high in vitro protein digestibility (>98%), regardless of the pH and use of enzymes during extraction, probably due to the low molecular weight of coffee proteins. Raising extraction pH from 7.0 to 9.0 resulted in extracts with lower concentrations of caffeine and some phenolic compounds such as chlorogenic and cinnamic acids, as well as catechin and epicatechin. This led to a reduction in the antioxidant activity of the extracts obtained at alkaline pH (AEP – pH 9.0). Overall, higher phenolic and caffeine extractability was achieved at neutral pH (AEP – pH 7.0), with no observed improvement in extraction yields when carbohydrases and/or proteases were employed. Coffee extracts generated by AEP at pH 7.0 exhibited the highest lipase inhibitory activity (66%), primarily attributed to their higher chlorogenic acid concentration. Conversely, EAEP extracts exhibited higher angiotensin-converting enzyme inhibition (up to 85%) compared to AEP extracts (68.5 – 74.3%). This strong inhibitory activity is likely related to the presence of both phenolic compounds (mainly chlorogenic acid) and smaller peptides. Nevertheless, all extracts exhibited low effectiveness for α-glucosidase inhibition (≤14%) and antimicrobial activity against S. aureus and E. coli. The current research underscores the feasibility of modulating the composition of green coffee extracts using sustainable and scalable AEP and EAEP, paving the way for developing tailored extracts with specific biological properties.

Metabolic Profiling, Antioxidant, and Anti-lipase Activity from Combined Leaves Extracts of Tamarindus indica and Murraya paniculata: A Simplex Lattice Design Approach

Tamarindus indica leaves are recognized for their potent antioxidant and hypolipidemic properties, whereas Murraya paniculata leaves are known for their abilities to lower lipids and glucose levels. This study aimed to assess the combined extract of both leaves against pancreatic lipase inhibition and analyze their metabolomic profiles as an initial step toward developing a polyherbal treatment for hypertriglyceridemia. The extracts were subjected to Liquid Chromatography-High Resolution Mass Spectrometer (LC-HRMS) untargeted system coupled with Compounds Discoverer software to reveal their metabolomic profile. Subsequently, both individual extracts and their combination were evaluated for anti-lipase activity using pancreatic lipase enzyme with p-nitrophenyl butyrate as the substrate. The combination of the two extracts (0-300 μg/mL, 300 μg/mL in total) was prepared following the Simplex Lattice Experimental Design with 5 different composition variations. Results: The findings indicated that Tamarindus indica leaf extract (TIE) predominantly exhibited lipase inhibitory activity. Interestingly, the addition of Murraya paniculata extract (MPE) diminished this enzyme inhibitory effect. TIE was found to be rich in polyhydroxy flavonoids followed by fatty amides, whereas MPE contained mainly polymethoxy flavonoids, fatty amides, and coumarins. The presence of fatty amides in both extracts was identified as a potential cause for this incompatibility. In summary, Tamarindus indica leaf extract demonstrated strong lipase inhibition; however, its effectiveness was reduced when combined with Murraya paniculata extract, possibly due to primary fatty amides. Further research is necessary to explore strategies for eliminating these compounds and confirming their impact in vivo.

Lipase Enzyme Kinetics with the Addition of Avocado Seed Extract as an Inhibitor in Olive Oil

Free fatty acids are compounds resulting from the hydrolysis of triglycerides catalyzed by the enzyme lipase. Free fatty acids harm health if they enter the body in large amounts. Avocado seed extract can reduce free fatty acid levels by inhibiting lipase activity. This research is a type of true-experimental research that aims to determine the effect of variations in substrate concentration on lipase enzyme activity with the addition of avocado seed extract and to determine the impact of the addition of avocado seed extract as an inhibitor on lipase enzyme kinetics. Lipase activity was determined based on the amount of oleic acid formed using Cu acetate pyridine reagent by Uv-Vis spectrophotometry at a wavelength of 715 nm. Lipase enzyme kinetics were determined using the Lineweaver-Burk curve equation, a transformed form of the Michaelis-Menten equation. The results showed that 60% substrate concentration was the most effective in reducing lipase enzyme activity by 60%. In addition, the addition of avocado seed extract proved to act as a competitive inhibitor, with the KM value decreasing from 0.014 M to 0.004 M and Vmaks remaining relatively stable at 23.2 µM. This shows that avocado seed extract effectively reduces lipase enzyme activity, which has implications for reducing FFA levels in olive oil. Thus, this study concludes that avocado seed extract has great potential as a natural inhibitor agent in reducing lipase enzyme activity.

Influence of flaxseed mucilage on the formation, composition, and properties of exopolysaccharides produced by different strains of lactic acid bacteria

Microorganisms produce a wide variety of polysaccharides. Due to biosafety considerations, lactic acid bacteria (LAB) are popular producers of exopolysaccharides (EPS) for various applications. In this study, we analyzed the composition and properties of EPS produced by L. delbrueckii ssp. bulgaricus and LAB from clover silage (L. fermentum AG8, L. plantarum AG9) after growth on Man, Rogosa, and Sharpe broth (MRS) and with the addition of flaxseed mucilage (FSM) using chromatography, microscopy, and biochemical methods. We found that adding 0.4 % FSM does not drastically alter the medium's rheology but substantially increases EPS yield (by 3.1 to 3.8 times) and modifies the composition and macrostructure of EPS, as well as changes the spatial organization of LAB cells. The presence of FSM led to the production of xylose- and glucose-enriched EPS, which also contained varying proportions of fucose, rhamnose, arabinose, mannose, glycosamines, and uronic acids, depending on the strain. Most EPS had a low molecular weight (up to 32 kDa), except for EPS produced by L. fermentum AG8 in FSM-containing medium, which had molecular weight of 163 kDa. All EPS exhibited a porous microstructure and demonstrated scavenging capacity for OH- and DPPH-radicals, as well as high levels of α-glucosidase and lipase inhibitory activities, even at low concentrations (<1 g·L−1 of EPS). These characteristics make them promising for use in functional food production and medicine.

In-vitro and in-silico investigation of anti-obesity effect of Shorea tumbuggaia

The rising prevalence of obesity has become a significant concern in both high income and low income countries. Addressing obesity has challenges due to the limitations in current treatment options. Dietary modifications have become a common approach in managing obesity and its associated risks. The study was aimed atinvestigating the anti-obesity effects of the methanol extract of Shorea tumbuggaia, focusing specifically on its ability to inhibit pancreatic lipase activity. Shorea tumbuggaia stem bark methanolic preparation was screened for total phenolic content and subjected to phytochemical tests for presence of secondary metabolites. The pancreas of a chicken was used to extract the lipase enzyme. Lipase inhibitory activity of various methanol extract concentrations was assessed using olive oil as the substrate. Additional docking investigations of Shorea tumbuggaia components were made to investigate the role in regulating obesity and its associated issues.The study revealed that the extract has exhibited concentration dependent inhibition of pancreatic lipase activity. The study findings on Shorea tumbuggaia lipase inhibitory activity are encouraging which may be due to the existence of secondary metabolites causing the inhibitory action.

UHPLC-Q-TOF-MS/MS identification of metabolites in cereal beverage ‘Borde’ and its anti-obesity efficacy in Caenorhabditis elegans model

This research explores the remarkable impact of fermented cereals such as sorghum, maize, and wheat with Pediococcus acidilactici WS07, a strain isolated from Ethiopia's traditional borde beverage. The fermented cereal extracts were thoroughly evaluated for antioxidant activity, inhibition of pancreatic lipase and α-glucosidase, metabolite identification through UHPLC-Q-TOF-MS/MS, and in vivo efficacy using the C. elegans model. The results revealed significant enhancements in the bioactive compounds of fermented cereals, demonstrating promising directions for obesity prevention strategies. Notably, the fermented sorghum extracts improved lipase (88.23 %) and α-glucosidase (85.62 %) inhibitory activities compared to its unfermented counterparts. The antioxidant properties of all fermented samples were confirmed through improved DPPH (67.77–71.86 %) and ABTS (59.91–65.49 %) scavenging activities. Fermentation also led to a notable increase in polyphenols and flavonoids, with detailed metabolite analysis revealing a dynamic shift in the composition of these bioactive compounds. Additionally, C. elegans indicates that fermented extracts extend lifespan, reduce lipid accumulation, and lower triglycerides, highlighting their potential as functional foods for health enhancement and obesity management. This study not only underscores the efficacy of P. acidilactici WS07 fermentation in transforming cereals into nutrient-rich functional foods but also provides insight into how microbial fermentation can unlock the health-promoting potential of traditional diets.

Effects of in vitro simulated digestion and fecal fermentation on the structure and regulating the glucose and lipid activity of a polysaccharide from Mori Folium

Mori folium, as a homologous drug-food, has hypoglycemic and lipid-lowering activity. Polysaccharides are the main bioactive ingredient of the Mori folium that exhibit diverse biological activities. In this study, a homogeneous polysaccharide (MP4) was purified and characterized from Mori folium. The changes of MP4 affected by saliva, simulated gastrointestinal juice, and human fecal fermentation, including physicochemical property or its bioactivity, were systematically investigated. Meanwhile, the influence of fermentation on the bioactivity were evaluated. The results showed that the backbone of MP4 is mainly composed of →4)-α-D-GalpA-(1→ residues. The molecular weight, the levels of reducing sugar content and free monosaccharides of MP4 exhibited no significant differences indicating that gastrointestinal digestion has a minimal effect on the physicochemical characteristics of MP4. However, during in vitro gut microbiota fermentation, MP4 are significantly degraded and utilized by gut microbiota, showing increased the production of short-chain fatty acids, notably acetic acid and propionic acid. The relative abundance of beneficial bacteria such as Bacteroidetes and Actinobacteria were significantly increased, whereas the levels of pathogenic bacteria such as Fusobacteria and Megamonas were significantly decreased, which changed the composition of the gut microbiota. The Firmicutes/Bacteroides ratio was also decreased significantly. Interestingly, after in vitro fermentation, the α-glucosidase inhibitory activity was increased, the lipase inhibitory activity and cholesterol adsorption activity was decreased. Correlation analysis showed that the relative abundance of some bacteria was significantly correlated with the bioactivities. These results provide a basis for the development of Mori folium polysaccharides as functional probiotic products.

How Enzyme Selectivity and Immobilization Affect Catalytic Yields in Lipase-Catalyzed Processes

Abstract: Herein, the influence of structural attributes, including the interactions of lipases with support systems, substrates, products/byproducts, and the media environment, on enzyme stability, selectivity and activity are discussed. Substrates/products, such as methanol, glycerol, phenolic acids and polyphenols, can inhibit lipase activity by influencing the mass flow of the reactants and products or by enzyme denaturation, which is also caused by extreme pH, high temperatures, and digestive action of most organic solvents. Immobilization techniques that involve chemical bonding between the functional groups of the support and the amino acids of the lipase maintain the enzyme’s active conformation via the formation of stable secondary structures. Functionalized metal nanoparticles and metal and covalent organic frameworks (COFs and MOFs) covalently bond to lipases, reducing the reliance of the active site conformation on hydrogen bonding and disulfide bonds. The crystallinity of COFand MOF-immobilized lipases allows them to be used in contrasting media environments and at high temperatures, which increases the reaction kinetics and improves the catalytic yield. On the other hand, inert support systems such as silica promote catalytic yields by minimizing protein leaching, which fairly maintains the amount of the preloaded lipase. The structure of substrates also plays a large role, whereas some lipases strictly prefer narrow substrates. In contrast, others, such as Candida species lipases, are liberal and allow substrates of varying bulkiness/steric hindrances.

Medicinal Plants and Natural Products to Treat Obesity through Inhibiting Pancreatic Lipase: A Review (2020-2022)

: Pancreatic lipase is an enzyme that catalyzes the hydrolysis of triglycerides to monoglycerides and free fatty acids which promote and accelerate their absorption by the intestine, thus leading to obesity. Drugs that have numerous side effects explain the beneficial medicinal effect of plants resulting from their Phyto molecules that exhibit strong anti-lipase activity. The present review reveals the medical treatment and consequently the associated side effects. It also represents an update of various medicinal plants and their metabolites that act as lipase inhibitors published between (2020-2022). We have discussed 93 species belonging to 48 different plant families and numerous bioactive molecules exerting this activity. We have compared 29 species for their anti-lipase potential. Fabaceae and Lamiaceae were the most dominant with 7 species, and the highest percentage (95%) for pancreatic lipase inhibitory activity was recorded by “Filipendula kmtaschatia” from Rosaceae family while “Piper betle” from Piperaceae family showed the lowest percentage (15.9%). The medical treatments with low dose effect were liraglutide saxenda (3mg/day), also flavonoids, in particular catechin derivatives, which were the most potent in terms of pancreatic lipase inhibitory activity with the lowest IC50s. This study summarized medical and natural treatments that are used to treat obesity through inhibiting pancreatic lipase and delaying fat assimilation in the intestines. So far, more studies are needed for the use of these as herbal medicine for obesity. Conclusion: This study summarized medical and natural treatments that are used to treat obesity through inhibiting pancreatic lipase and delaying fat assimilation in the intestines. So far, more studies are needed for the use of these as herbal medicine for obesity.

Evaluation of the In vitro and In silico Pancreatic Lipase Inhibitory Activity of Ethanol Leaf Extract of Tapinanthus cordifolius and its Effect on Oral Glucose Tolerance in Mice

Evaluation of the In vitro and In silico Pancreatic Lipase Inhibitory Activity of Ethanol Leaf Extract of Tapinanthus cordifolius and its Effect on Oral Glucose Tolerance in Mice

Acute Pre- and Post-administration of Lactiplantibacillus plantarum 2034 and Its Secretory Metabolites Ameliorates Hyperglycaemia, Hyperlipidaemia, and Oxidative Stress in Diabetic Rats.

The global prevalence rate of diabetes in 2021 was 6.1% making diabetes one of the top 10 causes of death. Prolonged use of antidiabetic medications is associated with various side effects; therefore, alternative treatment strategies for diabetes need exploration. The antidiabetic properties of Lactiplantibacillus plantarum 2034 was explored both in in vitro and in vivo studies. Secretory metabolites of probiotic L. plantarum 2034 exhibited alpha-glucosidase, alpha-amylase, and lipase inhibitory activities, in vitro. Further, the antidiabetic efficacy of 2034 was evaluated in streptozotocin-nicotinamide-induced diabetic rats. In the therapeutic model, oral administration of L. plantarum resulted in normalization of body weight, fasting blood glucose, total cholesterol (TC), and liver enzymes, and significant (p < 0.05) reduction in insulin and triglyceride (TG) levels. Histological evaluation of pancreas, liver, and kidney showed restoration of normal architecture in probiotic-treated group. Similarly, in a preventive + therapeutic model, 14days of pre-administration of 2034 in pre, pre + post, and cell-free supernatant resulted in significant reduction in glucose, TG, TC, and liver biochemistry of diabetic rats as compared to untreated diabetic rats. An oral glucose tolerance test showed that the glucose levels normalized within 90min in all the treated groups. Further, the oxidative stress parameters were also studied that showed that in all the treated groups, the concentration of antioxidant enzymes significantly (p < 0.05) increased as compared to diabetic untreated rats. Thus, administration of L. plantarum 2034 and its metabolites successfully ameliorated hyperglycaemia and hypercholesterolemia in both the models probably due to inhibition of gut enzymes and by increasing the concentration of liver antioxidant enzymes.

Oil in water emulsion stabilized by glycated rice bran protein aggregates: Effect on interfacial behavior and in vitro digestion of emulsion

To investigate the effect of molecular weight of saccharides and heating time on interfacial behavior of protein, glycated rice bran protein aggregates (gRBPAs) were obtained by incubating rice bran protein (RBP) with glucose (Glu), maltose (Mal) and dextran (Dex) via acid-heat treatment (pH 2.0, 90 °C). Subsequently, the stability and in vitro simulated digestion properties of oil in water (O/W) emulsion stabilized by gRBPAs were analyzed. Structural analysis (circular dichroism and fluorescence spectra) proved that the tertiary structure and secondary structure of RBP changed after glycation, and the contents of β-sheet structure of gRBPAs increased significantly. Besides, the glycation improved the interfacial activity and emulsification of protein obviously. Compared with Glu or Mal, the grafting of Dex could produce larger steric hindrance, which better inhibited the aggregation of emulsion droplets. Furthermore, glycation enhanced the pancreatic lipase (PL) inhibitory activity of gRBPAs obviously, and the emulsions stabilized by gRBPAs exhibited higher anti-digestion ability (62.12–75.00%) compared with RBP (95.27%). Moreover, the free fatty acid (FFA) rate of O/W emulsion was closely related to the surface hydrophobicity, degree of glycation, PL inhibitory activity and interfacial behavior of gRBPAs. Therefore, these findings would be enlightening to intuitively tailor the physicochemical stability and digestibility of O/W emulsion system according to heating time and molecular weight of saccharides. Meanwhile, this work would facilitate the application of O/W emulsion stabilized by glycated protein aggregates in functional foods.

Discovery of Curcuminoids as Pancreatic Lipase Inhibitors from Medicine-and-Food Homology Plants.

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 IC50 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.

Residue profiles of peptides with cholesterol esterase and pancreatic lipase inhibitory activities through virtual screening and sequence analysis

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 202 dipeptides and 203 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 IC50 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.

Synthesis and pancreatic lipase inhibition activity evaluation ofaurone derivatives with substituents on benzylidene ring

Pancreatic lipase is an essential enzyme for the digestion and absorption of dietary fat. Inhibiting this enzyme is one of the strategies in tackling obesity. To date, orlistat is the only Food and Drug Administration (FDA)-approved drug for obesity treatment via this mechanism. Therefore, there has been a growing interest in exploring novel compounds with natural structural frameworks that can give similar activity with fewer side effects. In this study, we describe the synthesis and pancreatic lipase inhibitory activity evaluation of 10 aurone derivatives with different substituents on the benzylidene ring. Aurone derivatives were synthesised through aldol condensation of benzofuranone and corresponding benzaldehyde derivatives with medium to good yields (45-73%). Pancreatic lipase inhibitory activities of synthesized compounds were determined by UV-Vis spectroscopy with quercetin and orlistat as references. Three aurones were found to have higher I% than quercetin at the same concentration (50 μg/ml). Compound 5c (2-(5’bromo-2’-hydroxybenzylidene)benzofuran-3(2H)-one) exhibited the greatest activity (I%=60.95%), better than quercetin (I%=27.20%) at the concentration of 50 μg/ml