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Abstract Background Cyanidin-3-rutinoside (C3R), a naturally occurring anthocyanin, possesses anti-oxidant, anti-hyperglycemic, anti-glycation and cardioprotective properties. However, its mechanisms responsible for anti-hyperlipidemic activity have not been fully identified. The aim of the study was to investigate the lipid-lowering mechanisms of C3R through inhibition of lipid digestion and absorption in vitro. Methods The inhibitory activity of C3R against pancreatic lipase and cholesterol esterase was evaluated using enzymatic fluorometric and enzymatic colorimetric assays, respectively. An enzyme kinetic study using Michaelis-Menten and the derived Lineweaver-Burk plot was performed to understand the possible types of inhibition. The formation of cholesterol micelles was determined using the cholesterol assay kit. The bile acid binding was measured using the colorimetric assay. The NBD cholesterol uptake in Caco-2 cells was determined using fluorometric assay. The mRNA expression of cholesterol transporter (Niemann-Pick C1-like 1) was determined by RT-PCR. Results The results showed that C3R was a mixed-type competitive inhibitor of pancreatic lipase with the IC50 value of 59.4 ± 1.41 μM. Furthermore, C3R (0.125–1 mM) inhibited pancreatic cholesterol esterase about 5–18%. In addition, C3R inhibited the formation of cholesterol micelles and bound to primary and secondary bile acid. In Caco-2 cells, C3R (12.5–100 μM) exhibited a significant reduction in cholesterol uptake in both free cholesterol (17–41%) and mixed micelles (20–30%). Finally, C3R (100 μM) was able to suppress mRNA expression of NPC1L1 in Caco-2 cells after 24 h incubation. Conclusions The present findings suggest that C3R acts as a lipid-lowering agent through inhibition of lipid digestion and absorption.

Twenty-five structurally diverse compounds have been tested in vitro for their pancreatic lipase (PL) inhibitory activity. Despite the diversity of tested compounds, the relationship comprising structural attributes of the compounds could be established to correlate with the observed inhibitory activity. Compounds that exerted inhibitory action through surface activity were of different profile from the rest of compounds. When co-incubated with orlistat (OsT), important synergistic effects for some compounds (orphenadrine, gliclazide, cefuroxime and sulfacetamide) were revealed, while antagonistic effects were demonstrated for others (camphor sulfonic acid and dinitro salicylic acid). Docking studies for the most active molecules were performed and molecular interaction forces with the PL active site were identified. The results suggested co-binding of OsT along with the other inhibitor in the binding site in cases of synergistic effect but not in the case of antagonistic effect. These results were additionally supported by affinity capillary electrophoresis. In conclusion, synergistic lipase inhibitory activity between OsT and some other pharmaceutical compounds was demonstrated for the first time, which might help improve the pharmacological effect of OsT.

Plant polysaccharides exert a wide range of biological effects on the intestinal function. In this study, four polysaccharides containing β-D-Glup, including Dendrobium officinale polysaccharide (DOP), Dendrobium aphyllum polysaccharide (DAP), and glucans from yeast (G-Y) and barley (G-B), were investigated in vitro for their intestinal-promoting functions such as inhibition of digestive enzymes, effect of blood glucose and blood lipid levels by using ultraviolet spectrophotometry, as well as the relationship of their structures to those functions. The results indicated that all polysaccharides significantly slowed glucose diffusion rate, decreased protease, and pancreatic lipase activities. Increased branching degrees had a deleterious effect on the α-amylase activity but increased bile acid binding. Increased calcium concentration in glucans (G-Y and G-B) and increased mannose molar ratio in Dendrobium polysaccharides (DOP and DAP) were correlated with increased pancreatic lipase inhibition. The polysaccharides with higher glucose content and branching degrees had higher bile acid binding and disruption of cholesterol micelle formation. These polysaccharides exerted a variety of potential health-promoting effects attributed to their different structures, which should be further investigated in vivo.

The mealworm (Tenebrio molitor Linnaeus 1758) is gaining importance as one of the most popular edible insects. Studies focusing on its bioactivities are increasing, although alternative forms of consumption other than the whole insect or flour, such as bioactive non-protein extracts, remain underexplored. Furthermore, the incidence of metabolic syndrome-related pathologies keeps increasing, hence the importance of seeking novel natural sources for reducing the impact of certain risk factors. The aim was to study the potential of a non-protein mealworm extract on metabolic syndrome-related pathologies, obtained with ethanol:water (1:1, v/v) by ultrasound-assisted extraction. We characterized the extract by gas-chromatography mass-spectrometry and assessed its hypolipidemic potential, its ability to scavenger free radicals, to attenuate the inflammatory response in microglial cells, to affect mitochondrial respiration and to enhance insulin sensitivity in mouse hepatocytes. The extract contained fatty acids, monoglycerides, amino acids, certain acids and sugars. The mealworm extract caused a 30% pancreatic lipase inhibition, 80% DPPH· scavenging activity and 55.9% reduction in the bioaccessibility of cholesterol (p = 0.009). The extract was effective in decreasing iNOS levels, increasing basal, maximal and ATP coupled respiration as well as enhancing insulin-mediated AKT phosphorylation at low insulin concentrations (p < 0.05). The potential of a non-protein bioactive mealworm extract against metabolic syndrome-related pathologies is shown, although further studies are needed to elucidate the mechanisms and relationship with compounds.

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

Pancreatic lipase is a key lipase for triacylglyceride digestion and absorption, which is recognized as a promising target for treatment of metabolic disorders. Natural phytochemicals are hopeful sources for pancreatic lipase inhibitors. The leaves of Artemisia argyi H.Lév. and Vaniot (AL) is commonly used as herbal medicine or food supplement in China and other Asian countries for hundreds of years. AL mainly contains essential oils, phenolic acids, flavonoids and terpenoids, which exhibit many pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, analgetic, anti-cancer, anti-diabetes and immunomodulatory effects. However, the anti-lipase activity of AL was lack of study and the investigation of anti-lipase ingredients from AL was also insufficient. In the present study, the anti-lipase activity of AL was evaluated in vitro and the potentially pancreatic lipase inhibitors of AL were investigated. High performance liquid chromatography was used to establish fingerprints of AL samples, and fifteen peaks were selected. The anti-lipase activities of AL samples were evaluated by a pancreatic lipase inhibition assay. Then, the spectrum-effect relationships between fingerprints and pancreatic lipase inhibitory activities were investigated to identify the anti-lipase constitutes in AL. As the results, four caffeoylquinic acids, which were identified as neochlorogenic acid, chlorogenic acid, isochlorogenic acid B, and isochlorogenic acid A by high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, were selected as potential pancreatic lipase inhibitors in AL. Moreover, anti-lipase activity assessment and molecular docking study of the four compounds were performed to validate the potential lipase inhibitors in AL. The results revealed that the four caffeoylquinic acids in AL as bioactive compounds displayed with anti-lipase activity. The present research provided evidences for the anti-lipase activity of AL, and suggested that some bioactive compounds in AL could be used as lead compounds for discovering of new pancreatic lipase inhibitors.

Obesity is considered a serious prevalent disease that is accelerating at an alarming rate. It has drawn worldwide attention and many approaches have been suggested to reduce dietary lipid hydrolysis and absorption. One of the substantial approaches is to inhibit pancreatic lipase (PL) that is the major responsible enzyme for fat digestion in the gastrointestinal lumen. Unfortunately, till now, the only pharmaceutical drug approved for obesity management is “Orlistat”, which has many unpleasant side effects. During the last decade, a massive effort has been dedicated to discovering safe lipase inhibitors from natural sources to avoid undesired drawbacks. The Middle East region is well known for its highly diverse flora with vast potential medicinal value. In this review, we try to provide an overview of the edible plants with potent anti-lipase activities and comprise a number of common ingredients in the Middle Eastern cuisine. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of ternary ammonium and phosphonium-based DESs were prepared and used as potential media for enzymatic hydrolysis. • Physicochemical properties of the DES systems including surface tension, conductivity, density, and viscosity were measured. • The kinetics and molecular docking simulation study of the DESs toward lipase enzyme were reported. • The ternary deep eutectic solvent systems would be a viable lipase activator in hydrolysis reaction. The present study investigates deep eutectic solvents (DESs) as potential media for enzymatic hydrolysis. A series of ternary ammonium and phosphonium-based DESs were prepared at different molar ratios by mixing with aqueous glycerol (85%). The physicochemical properties including surface tension, conductivity, density, and viscosity were measured at a temperature range of 298.15 K – 363.15 K. The eutectic points were highly influenced by the variation of temperature. The eutectic point of the choline chloride: glycerol: water (ratio of 1: 2.55: 2.28) and methyltriphenylphosphonium bromide:glycerol:water (ratio of 1: 4.25: 3.75) is 213.4 K and 255.8 K, respectively. The stability of the lipase enzyme isolated from porcine pancreas (PPL) and Rhizopus niveus (RNL) toward hydrolysis in ternary DESs medium was investigated. The PPL showed higher activity compared to the RNL in DESs. Molecular docking simulation of the selected DES with the substrate (p -nitrophenyl palmitate) toward PPL was also reported. It is worth noting that ternary DES systems would be viable lipase activators in hydrolysis reactions. [ABSTRACT FROM AUTHOR]

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: It is well established fact that the phytochemicals with phenolic and flavonoids origin have antioxidant property. Thus in this study it was aimed to determine the in vitro antioxidant potential of various extracts of Smilax zeylanica L. stems. Methods: The Photochemical screening was done following the standard procedures. The Antioxidant activity was tested using several in vitro assays, viz., 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The Total phenol and flavonoid contents were determined by colorimetric method. Further porcine lipase activity was determined. Results: The phytochemical screening revealed the presence of phenols and flavonoids the extracts. The Methanolic extract showed significant antioxidant potential than other extracts in all assays. The IC50 value of cyclo hexane extract, ethyl acetate extract and methanol extract of Smilax zeylanica was 29.14 ± 0.39 µ g/mL, 78.41 ±5 .53 µg/mL and 120.30 ±3 .32 µg/mL respectively in DPPH assay. Porcine pancreatic lipase inhibition assay lshowed dose-dependent effect. The % Inhibition of cyclohexane extract (SZH) was 37.52% 54.44% and 77.07% at the highest dose 200 µg/ml. The highest inhibition was obtained in the methanolic extract at 200 µg/ml conc which was close to the standard orlistat i.e. 82.39 at 200 µg/ml. Conclusion: The methanolic extracts showed potential pancreatic lipase inhibition. [ABSTRACT FROM AUTHOR]

BACKGROUND: Obesity and type 2 diabetes mellitus are the most extended current chronic diseases and also Alzheimer pathology which is a progressive degenerative neurological disorder. Therefore, finding effective enzyme inhibitors responsible for the development of these diseases are essential. Therefore, the aim of this study was to investigate the impact of fruit purée (Cydonia oblonga, Ziziphus jujube and Malus domestica) and pomegranate juice cultivar ('Mollar de Elche' and 'Wonderful') of dried pomegranate sheets (DS) on the inhibition of enzymes associated with metabolic (α‐amylase, α‐glucosidase, and pancreatic lipase activity), and neurological disorder (acetylcholinesterase and butyrylcholinesterase activity). Quality properties (colour coordinates, texture properties and sensory characteristics) of DS were also studied. In addition, it was researched the effect of storage conditions (4 months at 4 and 20 °C) on phenolic content. RESULTS: DS from jujube had the highest antioxidant capacity and were characterized by the highest storage stability with respect to phenolic compounds. The α‐amylase and α‐glucosidase half maximal inhibitory concentration (IC50, in mg mL−1) inhibition of DS ranged from 107 to 216 and from 55.2 to values indicating no effect, respectively. The inhibition toward pancreatic lipase (IC50 < 5 mg mL−1), acetylcholinesterase (ranged 9.15–22.2%) and butyrylcholinesterase (ranged 20.6–48.6%) was increased with the presence of total flavonoids and hydroxycinnamic acids content (identifying mainly in DS from quinces). It is noteworthy that none of the samples presented off‐flavour notes, supporting the high quality of the products. CONCLUSION: DS can be an innovative supplement to a diet as a snack used in the prevention of neurological changes and disorders of carbohydrate and lipid metabolism. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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

Brown seaweeds are a good source of bioactive compounds, particularly of phlorotannins, which may exert a wide spectrum of pharmacological properties. In the present study, phlorotannins of S. vulgare were extracted using a 70% acetone solution and the crude extract was further purified through liquid–liquid partition, giving rise to n-hexane, ethyl acetate and aqueous residue fractions. The crude extract and the purified fractions were evaluated for potential antioxidant abilities as well as for inhibitory potential towards the digestive enzymes α-amylase and pancreatic lipase, and anti-inflammatory potential through the hindering of albumin denaturation. Overall, the ethyl acetate fraction was the richest in phlorotannins (9.4 ± 0.03 mg PGE/g) and was also the most promising regarding the tested bioactive properties. Of note, its inhibitory potential towards α-amylase was about nine times that of the commercial drug acarbose and its inhibitory activity against high temperature-induced protein denaturation was superior to that of the non-steroidal drug ketoprofen. According to UHPLC-DAD-ESI-MS/MS analysis, this fraction contained a range of phlorotannins with at least six units of phloroglucinol, including dibenzodioxine-1,3,6,8-tetraol, fuhalol, pentaphlorethol, fucopentaphlorethol and dihydroxypentafuhalol, in addition to several less common phlorotannin sulfate derivatives.

Sixteen substituted 1-hydroxy-3-methylxanthones were synthesized in one step. The yields ranged from 33 to 76%. Then, the antitumor, antioxidant, anti-tyrosinase, anti-pancreatic lipase, and antifungal activities of compounds 1–16 were evaluated. Compounds 10–12 and 14 inhibited tyrosinase and pancreatic lipase activity to a certain extent, respectively. Compound 16 exhibited obvious cytotoxicity against fifteen cancer cells, moderate antioxidant activity, and moderate inhibitory activity against Candida albicans. In particular, compound 16 exhibited strong inhibitory activity against A-549 and A549/Taxol cells. These results demonstrated that compounds 10–12, 14, and 16 are promising leads for further structural modification. [ABSTRACT FROM AUTHOR]

The effects of galactofucan from Laminaria japonica on the digestion and intestinal microbiota of human were investigated in the present study. Crude fraction of the sulfated polysaccharide from L. japonica (CF) and its molecular-weight homogeneous fraction (CGF-3) were prepared and characterized. In the simulated digestion model for the human saliva and gastrointestinal tract, no obvious changes in the molecular weight or the reducing sugar content of CGF-3 were observed, indicating CGF-3 is resistant to the human digestive system. Then CGF-3 did not affect the α-amylase activity while it dose-dependently inhibited the activity of pancreatic lipase partly depending on its sulfate groups. In the in vitro fermentation with the human fecal microbiota, CF did not change the total carbohydrate, reducing sugar and short chain fatty acids contents, which indicated CF was not utilized by the microbiota. However, the microbiota composition was modulated greatly by CF intervention. These findings shed a light on the better understanding of the impacts of dietary galactofucan on the digestion and intestinal microbiota. • Galactofucan from Laminaria japonica was not degraded in the simulated digestion. • The galactofucan inhibited pancreatic lipase activity. • The galactofucan was not utilized by the human microbiota in the fermentation. • The microbiota composition was obviously modulated by the galactofucan. [ABSTRACT FROM AUTHOR]

Protein hydrolysates were produced via enzymatic hydrolysis of sacha inchi protein isolate using three different protease enzymes: pepsin, papain and Flavourzyme. Each hydrolysate sample was then fractionated by ultrafiltration membrane at various molecular weight (MW) cut-off ranging from 1-10 kDa. The results show that peptide fraction with MW of 1-3 kDa produced with pepsin had the highest inhibitory activity against α-amylase. Peptide fraction with MW < 1 kDa produced by Flavourzyme had the highest inhibitory activity against α-glucosidase (51.06±0.08%), followed by fractions with MW < 1 kDa and 1-3 kDa (48.21±0.12% and 48.27±0.17%) produced by pepsin, and unfractionated hydrolysate produced by papain (42.81±0.38%). However, the fractionated peptides had reduced capacity in inhibiting lipase activity (IC50>3.0 mg/mL) compared with the unfractionated counterparts (IC50<3.0 mg/mL). The findings suggest that sacha inchi protein-derived peptides have the potential for being utilised as functional foods as they can play an important role in the management of caloric intake. [ABSTRACT FROM AUTHOR]

Introduction. The aim of the research is to determine the inhibitory activities of Caucasian Rhododendron (Rhododendron caucasicum) and Rkatsiteli wines against pancreatic lipase. Materials and methods. The leaves of Caucasian Rhododendron were collected in the Upper Svaneti region. Wines were made of Rkatsiteli grape variety. Titrimetric method was used to determine lipase activity, total phenolic content (TPC), and Ferric reducing ability of plasma (FRAP) were determined spectrophotometrically. Results and discussion. We could demonstrate in this research project a high correlation between TPC and antioxidant activity (AOA) in all samples. Pearson's correlation coefficient (R²) for the Caucasian Rhododendron samples and wine samples were 0.9758 and 0.9556, respectively. The average TPC in Caucasian Rhododendron was found to vary from 13.00±0.48 to 19.48±0.84 % Gallic acid equivalent (GAE) based on dry matter content. The 3-rd sample of Caucasian Rhododendron revealed the highest TPC, 19.48±0.84 % GAE, and possessed an AOA of 16.10±0.32. No significant difference was observed between the third and first sample of 17.97±0.42% GAE and 15.35±0.74 AOA (p<0.05). Even though the fourth sample showed the lowest TPC and AOA, its lipase inhibitory activity closely resembled Orlistat. t seems that polyphenol, which is most responsible for anti-lipase activity of Caucasian Rhododendron is easily oxidised in the air. Consequently, similar technology to green tea processing allows retaining most of the polyphenol in the vine sample. In the rest of the samples, this substance underwent oxidation by molecular oxygen. These results indicated that the treatment of Rhododendron samples could influence the composition of bioactive compounds. The results obtained herein allow one to conclude that white wines made with Kakhetian technology are rich with bioactive compounds and possess higher antioxidant activity and Lipase inhibitory activity when compared to wines made with European technology. Conclusion. Extracts from Caucasian Rhododendron can act as a promising natural inhibitor and reduce dietary cholesterol' absorption. Based on a dry matter content, Caucasian Rhododendron offered better inhibitory activity than white wine samples. [ABSTRACT FROM AUTHOR]

Overweight is a significant health hazard. It increases the risk of development of various diseases. The nutritional value, phytochemical composition and in-vitro antiobesity potential of the seeds and fruits pericarp of Livistona carinensis (L. carinensis) and Thrinax parviflora (T. parviflora) were assessed. The phytochemical screening of both plants showed the presence of tannins, carbohydrates, sterols, flavonoids and anthraquinones. GLC (Gas liquid Chromatography) analysis of lipids allowed the identification of stigmasterol as the major phytosterol in seeds and pericarp of L. carinensis (9.01% and 10.81%), respectively while ß-sitosterol is the major in seeds and pericarp of T. parviflora (13.79% and 9.19%), respectively. Palmitic acid was the major fatty acid methyl ester in the pericarp of L. carinensis (35.01%), followed by myristic acid in the pericarp of T. parviflora (20.68%). Concerning unsaturated fatty acids linoleic acid is the major in seeds of T. parviflora (53.93%) followed by seeds and pericarp of L. carinensis (18.49% and 11.10%), respectively, while oleic acid is the major in pericarp of T. parviflora. Quantitative estimation of constituents revealed that L. carinensis seeds showed the highest concentration of total polyphenolics (39.02±1.24 mg/g gallic acid equivalents), flavonoids (10.75±0.40 mg/g quercetin equivalent) and tannins (15.82±0.62 mg/g tannic acid equivalents). While the highest steroidal content is found in T. parviflora pericarp (11.51±0.44 mg/g ß-sitosterol equivalent). Both plants pericarps possess higher content of carbohydrates than that of seeds while the protein content is higher in T. parviflora, pericarp and seeds than that of L. carinensis. Calcium and iron are found prominent in T. parviflora pericarp (6.47 and 2.07 mg/gm, respectively) while the highest concentration of potassium was found in L. carinensis pericarp (21.43 mg/gm). The free radicle scavenging activity using DPPH is found in the following order T. parviflora seeds (13.79 µg/ml)? T. parviflora pericarp (9.72 µg/ml)? L. carinensis pericarp (8.95 µg/ml) ? L. carinensis seeds (7.37 µg/ml) compared to ascorbic acid as standard (7.80 µg/ml). In addition, seeds and pericarp of L. carinensis showed the highest a-glucosidase inhibitory activity with IC50 values 0.93 and 1.17 mg/ml, respectively followed by the seeds and pericarp of T. parviflora (IC50 =1.46 and 1.76 mg/ml, respectively), compared to acarbose (IC50 = 0.72 mg/ml). Moreover, seed extracts of L. carinensis and T. parviflora showed powerful inhibitory activity against pancreatic lipase (IC50 = 10.95 and 9.33 µg/ml, respectively) compared to orlistat (6.82 µg/ml). In conclusion, seed extracts of L. carinensis and T. parviflora showed the most powerful a-glucosidase and lipase inhibitory activities, these recommend their incorporation in anti-obesity preparations. Their pericarps showed significant antioxidant activity with high calcium, iron and potassium contents in addition to their moderate a-glucosidase inhibitory activities which recommend their daily intake in weight control programs. [ABSTRACT FROM AUTHOR]

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.)

A series of 1,1'-biphenyl-3-carboxamide and furan-phenyl-carboxamide analogs were synthesized using an optimized scheme and confirmed by 1 H and 13 C nuclear magnetic resonance and high-resolution mass spectrometry techniques. The synthesized peptidomimetics analogs were screened in vitro to understand the inhibitory potential of pancreatic lipase (PL). Analogs were assessed for the PL inhibitory activity based on interactions, geometric complementarity, and docking score. Among the synthesized analogs, 9, 29, and 24 were found to have the most potent PL inhibitory activity with IC 50 values of 3.87, 4.95, and 5.34 µM, respectively, compared to that of the standard drug, that is, orlistat, which inhibits PL with an IC 50 value of 0.99 µM. The most potent analog, 9, exhibited a competitive-type inhibition with an inhibition constant (K i ) of 2.72 µM. In silico molecular docking of analog 9 with the PL (PDB ID:1LPB) showed a docking score of -11.00 kcal/mol. Analog 9 formed crucial hydrogen bond interaction with Ser152, His263, π-cation interaction with Asp79, Arg256, and π-π stacking with Phe77, Tyr114 at the protein's active site. The molecular dynamic simulation confirmed that analog 9 forms stable interactions with PL at the end of 200 ns with root mean square deviation values of 2.5 and 6 Å. No toxicity was observed for analog 9 (concentration range of 1-20 µM) when tested by MTT assay in RAW 264.7 cells., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Pancreatic lipase (PL) is a keen target for anti-obesity therapy that reduces dietary fat absorption. Here, we investigated the binding patterns of 220 PL inhibitors having experimental IC 50 values, using molecular docking and binding energy calculations. Screening of these compounds illustrated most of them bound at the catalytic site (S1-S2 channel) and a few compounds are at the non-catalytic site (S2-S3 channel/S1-S3 channel) of PL. This binding pattern could be due to structural uniqueness or bias in conformational search. A strong correlation of pIC 50 values with SP/XP docking scores, binding energies (ΔG MMGBSA ) assured the binding poses are more true positives. Further, understanding of each class and subclasses of polyphenols indicated tannins preferred non-catalytic site wherein binding energies are underestimated due to huge desolvation energy. In contrast, most of the flavonoids and furan-flavonoids have good binding energies due to strong interactions with catalytic residues. While scoring functions limited the understanding of sub-classes of flavonoids. Hence, focused on 55 potent PL inhibitors of IC 50 < 5 µM for better in vivo efficacy. The prediction of bioactivity, drug-likeness properties, led to 14 bioactive compounds. The low root mean square deviation (0.1-0.2 nm) of these potent flavonoids and non-flavonoid/non-polyphenols PL-inhibitor complexes during 100 ns molecular dynamics runs (MD) as well as binding energies obtained from both MD and well-tempered metadynamics, support strong binding to catalytic site. Based on the bioactivity, ADMET properties, and binding affinity data of MD and wt-metaD of potent PL-inhibitors suggests Epiafzelechin 3-O-gallate, Sanggenon C, and Sanggenofuran A shall be promising inhibitors at in vivo conditions.Communicated by Ramaswamy H. Sarma.

Pancreatic lipase (PL) inhibitor therapy is one of the most effective ways to treat obesity and obesity-associated metabolic disorders. Herein, bioactivity and liquid chromatograph-mass spectrometer (LC-MS) guided fractionation strategy was used to identify the naturally occurring PL inhibitors in Styrax, a popular folk medicine in Asia and Turkey. The results clearly showed that five pentacyclic triterpenoid acids in Styrax displayed strong inhibition on PL, with IC50 values ranging from 0.49 µM to 6.35 µM. Further investigations demonstrated that oleanonic acid and betulonic acid (the most two potent PL inhibitors in Styrax) potently inhibited PL in a reversible and mixed inhibition manner, while molecular dynamics simulations showed that these two agents could stably bind at the entrance to the active site of PL. Collectively, our findings revealed the molecular basis for the anti-obesity effects of Styrax, while the newly identified PL inhibitors in this herb could be used for development of novel anti-obesity agents.

Repression of pancreatic lipase activity reduces the excessive absorption of lipids, thereby reducing the risk of being overweight and obese. In the study, the inhibition of kaempferol on pancreatic lipase was studied by various spectroscopy techniques and molecular docking analysis. Kinetic analysis indicated that kaempferol reversibly inhibited pancreatic lipase activity in a competitive manner and showed the synergistic inhibition with orlistat. The fluorescence titrations suggested that kaempferol quenched the fluorescence of pancreatic lipase and the binding process was mainly driven by hydrophobic interactions and hydrogen bonds. The structural compactness of pancreatic lipase was verified by the results of circular dichroism and Fourier transform infrared spectra. Molecular docking and molecular dynamics simulation showed that kaempferol interacted with the residues Lys42 and Tyr404 in the active site of the enzyme by hydrogen bonds, preventing the substrate from binding to the active site. These findings may provide a theoretical basis for the further study of kaempferol as a natural anti-obesity supplement.

Lyciumruthenicum Murray (L. ruthenicum) has been used both as traditional Chinese medicine and food. Recent studies indicated that anthocyanins are the most abundant bioactive compounds in the L. ruthenicum fruits. The purpose of this study was to investigate the preventive effects and the mechanism of the anthocycanins from the fruit of L. ruthenicum (ACN) in high-fat diet-induced obese mice. In total, 24 male C57BL/6J mice were divided into three groups: control group (fed a normal diet), high-fat diet group (fed a high-fat diet, HFD), and HFD +ACN group (fed a high-fat diet and drinking distilled water that contained 0.8% crude extract of ACN). The results showed that ACN could significantly reduce the body weight, inhibit lipid accumulation in liver and white adipose tissue, and lower the serum total cholesterol and low-density lipoprotein cholesterol levels compared to that of mice fed a high-fat diet. 16S rRNA gene sequencing of bacterial DNA demonstrated that ACN prevent obesity by enhancing the diversity of cecal bacterial communities, lowering the Firmicutes-to-Bacteroidota ratio, increasing the genera Akkermansia, and decreasing the genera Faecalibaculum. We also studied the inhibitory effect of ACN on pancreatic lipase. The results showed that ACN has a high affinity for pancreatic lipase and inhibits the activity of pancreatic lipase, with IC50 values of 1.80 (main compound anthocyanin) and 3.03 mg/mL (crude extract), in a competitive way. Furthermore, fluorescence spectroscopy studies showed that ACN can quench the intrinsic fluorescence of pancreatic lipase via a static mechanism. Taken together, these findings suggest that the anthocyanins from L. ruthenicum fruits could have preventive effects in high-fat-diet induced obese mice by regulating the intestinal microbiota and inhibiting the pancreatic lipase activity.

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4–13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC50 = 25 μg/mL) and Klebsiella pneumoniae (IC50 = 50 μg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2–73.0% at a concentration of 50 μg/mL.

In this study, the effects of a chokeberry fruit crude extract (CE), its ethyl acetate fractions (EAF7 & EAF2) and a polyphenol-rich fraction (PRF) on esterase and lipolytic activities of pancreatic lipase (PL) were investigated. Ethyl acetate fractions, rich in flavonols, phenolic acids and low molecular procyanidins, showed a week inhibitory activity against PL while the CE and PRF, which contained the highly polymerized procyanidins exhibited the highest anti-lipase activity. The kinetic study showed that the inhibitory mode of CE was noncompetitive while PRF behaved like the mixed type inhibitor. Cumulative effects were observed when orlistat was used with either CE or PRF. These results indicate that black chokeberry fruits are a source of PL inhibitors with proanthocyanidins as the most active compounds.

Abstract Background Lifestyle-related diseases such as diabetes are steadily increasing worldwide. In Sudan, there are a variety of plant species used traditionally for the treatment of diabetes, obesity and other symptoms which need to be validated through scientific studies for their claimed traditional uses. Therefore, in the current study, the free radical scavenging activity, α-glucosidase inhibitory and pancreatic lipase inhibitory activities of 70% ethanol and water extracts of eighteen Sudanese medicinal plants were investigated using various in vitro assays. Moreover, the cytotoxicity and genotoxicity were assessed for the bioactive plant extracts. Methods Eighteen plants were selected on the basis of their traditional uses and extracted with 70% ethanol and water to obtain thirty-six extracts. The obtained extracts were screened using different in vitro bioassays namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, α-glucosidase inhibitory and pancreatic lipase inhibitory assays. Furthermore, the active plant extracts were investigated for their cytotoxicity and genotoxicity on HeLa cell line using HCS DNA Damage Assay. Results Both 70% ethanol and water extracts of Acacia nilotica, Ziziphus spina-christi, Abrus precatorius, and Geigeria alata along with the 70% ethanol extract of Martynia annua showed potent free radical scavenging activity. Regarding the α-glucosidase inhibition assay, both extracts of Acacia nilotica, Ziziphus spina-christi, Geigeria alata, and Cyperus rotundus showed potent activity. In general, 70% ethanol extracts were more potent compared to water extracts with exception of Cordia sinensis and Cymbopogon proximus, for which water extracts also showed potent enzyme inhibitory activity. Similarly, water extracts of Acacia nilotica and Ziziphus spina-christi showed potent inhibitory activity against pancreatic lipase enzyme. Some of the extracts also showed significant genotoxicity and cytotoxicity at the concentration range used for bioactivities. Conclusion The extracts of Acacia nilotica, Ziziphus spina-christi, Geigeria alata, Martynia annua and Abrus precatorius exhibited an appreciable range of activity on antioxidant and enzyme inhibitory assays.

Strictinin isolated from Pu’er tea was demonstrated to inhibit pancreatic lipase in vitro. In an olive oil tolerance test, the administration of strictinin (100 mg/kg) significantly reduced the blood triglyceride level and increased the fecal oil content of C57BL6 mice. In a long-term animal study, the body weight gained via high-fat diet was significantly reduced in the mice supplemented with strictinin of 130 mg/kg. Further analysis showed that weight of epididymal fat, but not that of liver or muscle, increased in mice fed with high-fat diet, and the increase of fat was reduced in the mice supplemented with strictinin. Correspondingly, sizes of adipocytes in epididymis were substantially enlarged in mice fed with high-fat diet, and the enlargement of adipocytes was decreased when strictinin was supplemented. Levels of blood triglyceride, cholesterol and glucose were elevated in mice fed with high-fat diet, and these elevated levels were reduced when strictinin was supplemented.

Astaxanthin is a natural pigment that possesses benefit potentials to prevent obesity, however, its underlying mechanism is not clarified. In the current study, Phaffia rhodozyma astaxanthin was prepared and its inhibitory effect on pancreatic lipase was evaluated. The results showed that astaxanthin significantly inhibited the activity of pancreatic lipase in a dose-dependent manner within the tested concentration ranges. The kinetic analysis demonstrated that astaxanthin noncompetitively inhibited pancreatic lipase activity. In addition, astaxanthin induced secondary structure changes which resulted in decreased enzyme activities. Furthermore, the molecular docking analysis revealed that astaxanthin blocked the channel of catalytic site to delay substrate entrance or prevent product diffusion through changing the catalytic site conformation. These findings not only shed light on the underlying inhibitory mechanism of astaxanthin on pancreatic lipase, but also provide scientific evidence for extending the application of astaxanthin in functional food industries.

Within this study phytochemical composition, antioxidant and enzyme inhibitory activities of extracts obtained from stem and flower of Verbascum cheiranthifolium var. cheiranthifolium were analysed. Both of the extracts were detected as rich sources of phenolics (verbascoside and luteolin hexoside), various volatile and fatty acid compounds. Luteolin hexoside rich stem extract had pronounced FCR, FRAP and α-glucosidase inhibitory activities. Flower extract had high levels of ORAC assay and effectively suppressed activity of pancreatic lipase enzyme, which was rich in verbascoside compound. Phenolic compounds and volatile compounds present in the extracts might be the main contributors of antioxidant capacity and enzyme inhibitory activities of the stem and flower extracts. Pronounced antioxidant and enzyme inhibitory activities and rich bioactive composition determined in this study reveal that Verbascum cheiranthifolium var. cheiranthifolum extracts might be a good source for natural health attributing sources.

The aim of this study was to isolate and purify anti-obesity peptides from Spirulina platensis protein. Five enzymes (trypsin, alcalase, pepsin, papain and protamex) were used for hydrolysis of the extracted protein. Subsequently, ultrafiltration and gel column chromatography were employed for further purification. The inhibitory effect on pancreatic lipase and 3T3-L1 preadipocytes were evaluated. The results showed that the 3–5 kDa fraction from pepsin digest exhibited good inhibition on lipase (72%), and its chromatographed fractions displayed strong inhibition on 3T3-L1 preadipocytes (72.7–88.1%) but low inhibitory or stimulatory activities on normal liver cells L-O2 (−26.02 to 12.16%). By mass spectrometry, four novel peptides NALKCCHSCPA, LNNPSVCDCDCMMKAAR, NPVWKRK and CANPHELPNK were identified, which exhibited inhibitory effects on 3T3-L1 preadipocytes proliferation (32.29–60.08%). Moreover, NPVWKRK and CANPHELPNK also significantly decreased the accumulation of triglyceride at 600 μg/mL (p

Lipids are one of the main macronutrients that constitute balanced feeds used in aquaculture. Adequate utilization of dietary lipid is influenced by the activity of pancreatic lipase, one of the enzymes that promotes digestion of dietary lipids in the gastrointestinal tract of fish. The culture of Totoaba macdonaldi is quite recent; its nutritional requirements have been partially established. Knowing the characteristics of pancreatic lipase for this species could help optimize the dietary lipids included in balanced feeds for its culture. Therefore, the aim of this work is to partially characterize and evaluate the enzymatic activity of pancreatic lipase for T. macdonaldi. Biological indices showed that experimental organisms had a good nutritional status. Pancreatic lipase molecular weight was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and its activity was evaluated in crude enzymatic extracts from different gastrointestinal tract regions. The molecular weight of lipase was estimated to be 70.4 kDa; the highest lipolytic activity was observed at 45°C and at a pH optimum of 8.0 in the anterior intestine and pyloric caeca, where the concentration and activity of the enzyme was significantly higher (P=0.004) compared to the distal parts of the intestine. Biochemical characteristics observed for the pancreatic lipase of T. macdonaldi are quite similar to other lipases of fish cultured worldwide; results provided in this study will help understand the role this lipolytic enzyme plays in the digestive process of this species.

The present study investigated the synergistic potential of methanol extract/fractions of Camellia sinensis (L.) Kuntze (CSM) leaves and orlistat on inhibition of Pancreatic Lipase (PL). Since PL is responsible for 50–70% of dietary fats digestion, its inhibition is considered as a promising target for the management of obesity. A synergy guided fractionation strategy has been incorporated with the help of combination index (CI) and isobologram methods. CSM exhibited a potential synergistic activity in combination with orlistat (CI value: 0.66). Amongst the subfractions of CSM, polyphenol-rich fraction exhibited a greater synergistic potential (CI-0.35) than remaining fractions. HPLC analysis identified epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) as major phytochemicals in polyphenol-rich fraction and the most active subfractions (F6 and F7). Two drug and three-drug combinations of these phytochemicals were investigated by partnering with orlistat. The three-drug combination (orlistat-EGCG-ECG) exhibited a greater synergistic potential (CI value-0.17) than the two-drug combinations of EGCG-orlistat and ECG-orlistat (CI values of 0.40 & 0.71, respectively). The resultant orlistat-EGCG-ECG combination resulted in a 12.11-fold dose reduction index for orlistat. Thus, synergistic drug combinations of polyphenol-rich fraction along with orlistat offers the prospect to enhance the orlistat anti-obesity efficacy in a decreased dose level, that will help to reduce its associated toxicities while maintaining its efficacy. Image, graphical abstract • Methanol extract of C. sinensis was subjected to synergy guided fractionation. • Polyphenol rich fraction showed synergistic potential than the subsequent fractions. • A three-drug synergy of EGC: EGCG: orlistat was performed. • A 12.11-fold dose reduction of orlistat was achieved. • First report on the role of phytochemicals as potential synergists for orlistat. [ABSTRACT FROM AUTHOR]

Background: Obesity, reached epidemic proportions globally is often associated with life threatening comorbidities. The unavailability of safe and effective long term medications for obesity in modern pharmacotherapy forces the scientific community to explore the potential of Ayurvedic traditional healers as they are considered safe and effective. Objective: To explore the anti-obesity potential of aqueous extract of aerial parts of Achyranthes aspera L. (AEAA), a traditional healer in high fat diet (HFD) induced obese rats. Methods: AEAA was prepared and subjected to in-vitro pancreatic lipase inhibition assay and in-vivo anti-obesity studies. For in-vivo studies, HFD fed obese prone Wistar albino rats were divided into five experimental groups (Group II to VI): animals fed with standard pellet chow served as normal control (Group I) while, animals continued with HFD alone served as obese control (Group II); Group III, IV and V were administered AEAA at a dose of 100, 200 and 300 mg/kg b.w. respectively along with HFD; and animals administered orlistat (30 mg/kg bw) along with HFD served as standard control (Group VI). All the drugs were administered orally once a day for a period of 60 days. At the end of the experimental period various physical, biochemical and histopathological observations were made. Results: In-vitro studies showed AEAA partially but not significantly inhibited the activity of pancreatic lipase. Data of in-vivo studies revealed, significant reduction in body weights, fat pad weights and organ weights upon AEAA treatment. Elevated levels of glucose, insulin, leptin, lipid profiles and antioxidant status were also brought back to normal. Conclusion: The obtained results clearly suggested that AEAA possess pronounced anti-obesity potential. [ABSTRACT FROM AUTHOR]

Gallic acid and quercetin equivalent were determined in the crude extract of matured leaves Aquilaria malaccensis and Aquilaria subintegra. The leaves of both Aquilaria species were dried at 60 °C for 24 hours, ground and sieved into particle size of 250, 300, 400, 500, and 1000 μm. Then, each particle size of leaves was soaked in distilled water with a ratio of 1:100 (w/v) for 24 hours and undergoes the pretreatment method by using ultrasonicator (37 kHz), at the temperature of 60 °C for 30 minutes. The crude extracts were obtained after about 4 hours of hydrodistillation process. The highest concentration of gallic acid and quercetin equivalent was determined in the crude extract from the particle size of 250 μm. The kinetics of pancreatic lipase inhibition was further studied based using the Lineweaver- Burk plot, wherein the concentration of p-NPP as the substrate and pancreatic lipase were varied. Based on the formation of the lines in the plot, the crude leaves extract of both Aquilaria species exhibit the mixed-inhibition on pancreatic lipase, which indicates that in the reaction, the inhibitors were not only attached to the free pancreatic lipase, but also to the pancreatic lipase-(p-NPP) complex. The reaction mechanism was similar to non-competitive inhibition; however the value of dissociation constant, Ki, for both inhibition pathways was different. The inhibition shows an increment in Michaelis- Menten constant (Km) and a reduction in the maximum pancreatic lipase activity (Vm) compared to the reaction without Aquilaria spp. crude extracts (control). This proved that the inhibition occurred in this reaction. [ABSTRACT FROM AUTHOR]

Background: Serum feline pancreatic lipase immunoreactivity (fPL) commonly is used in the assessment of sick cats suspected to have pancreatitis but its diagnostic utility is debated. Objectives: To evaluate the diagnostic utility of the Spec fPL test and selected serum biochemistry tests in the diagnosis of pancreatitis in cats. Animals Two hundred seventy‐four client‐owned cats presented to a university teaching hospital in the United Kingdom, from April 2013 to May 2017, in which Spec fPL was measured. Methods: Cats were classified into 1 of 4 groups based on clinical signs (all cats), ultrasonographic findings (all cats) and histopathological or cytological assessment of the pancreas where available (9 cats) regardless of Spec fPL concentration. The groups were (a) definite pancreatitis (n = 9), (b) probable pancreatitis (n = 49), (c) possible pancreatitis (n = 139), and (d) unlikely pancreatitis (n = 77). Spec fPL and selected serum biochemistry test results were compared among groups. Results: Serum fPL concentrations >5.3 μg/L were classified as positive and concentrations <3.5 μg/L were classified as negative. There was a significantly (P =.03) lower proportion of false‐positive results (cats unlikely to have pancreatitis, n = 77, with a positive fPL, n = 8, 10%) than false‐negative results (cats with definite or probable pancreatitis, n = 58, with a negative fPL result, n = 14, 24%). None of the selected biochemical tests were helpful diagnostically. Conclusion and Clinical Importance: A positive Spec fPL result indicates that pancreatitis is a probable diagnosis, but the test cannot be used to rule the diagnosis out. [ABSTRACT FROM AUTHOR]

Context:Spinaciaoleracea (spinach) is abundant in antioxidant phytoconstituents, termed as the natural antioxidant mixture (NAO). Objective: This study evaluates the anti-hyperlipidemicand anti-obesity effects of an antioxidant-rich extract of Spinaciaoleracea (NAOE) and aerobic exercise (AE) in rats fed with high fat diet (HFD). Methods: Rats received NAOE (200 and 400 mg/kg), the standard drug orlistat (10 mg/kg), AE and NAOEAE (NAOE 400 mg/kg + AE) daily with HFD for 21 d. Results: Orlistat, NAOE and NAOEAE treatments to HFD-fed rats significantly reduced the HFD-elevated food intake, weight gain, pancreatic lipase activity and lipid peroxidation, and successfully restored the HFD-skewed lipid profile and antioxidant levels. Conclusions: It may be concluded that NAOE exhibited a promising anti-hyperlipidemic effect by its inhibitory action on pancreatic lipase. The combination treatment NAOEAE produced the best results indicating the essential role of exercise along with consumption of antioxidant-rich foods in maintaining a normal lipid profile and controlling obesity. [ABSTRACT FROM AUTHOR]

In the present study, the efficiency of three different solvents (H 2 O, acidified H 2 O, and 70% Methanol) for metabolites extraction from the leaves of sugar beet (Beta vulgaris subsp. vulgaris var. rubra) was investigated along with their inhibitory activity on pancreatic α-amylase and lipase for obesity management. The metabolic profile of the three extracts was analyzed by ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization high-resolution mass spectrometric (ESI-HRMS-MS). Mass spectrometry-based molecular networking was employed to aid in metabolites annotation and for the visual investigation of the known metabolites and their analogues. The study led to the tentative identification of 45 metabolites including amino acids, purine derivatives, phenolic acids, flavonoids, fatty acids, and an alkaloid, articulating 24 compounds as a first time report from beet leaves along with 2 new putatively identified compounds: a flavone feruloyl conjugate (39) and a malonylated acacetin diglycoside (40). The three extracting systems exhibited comparable efficiency for pulling out the secondary metabolites from the beet leaves. The in vitro study supported this finding and demonstrated that the three extracts inhibited the activity of both pancreatic α-amylase and lipase enzymes with no significant difference observed regarding the percentage of the inhibition of the enzymes. Conclusively, the extraction protocol has a minimal effect on the anti-obesity properties of beet leaves. [ABSTRACT FROM AUTHOR]

• The structural features of LEHSDF were characterized. • LEHSDF effectively inhibited the lipid accumulation in HepG2 cells and PL activity. • LEHSDF did not bind to BS, but exhibited a strong binding effect to PL. • LEHSDF-PL showed interaction forces of hydrophobic forces, electrostatic forces, encapsulation and adsorption. Aimed to evaluate the hypolipidemic effects of high molecular weight soluble dietary fiber extracted from L. edodes (LEHSDF), this study investigated the structure and interaction mechanism of LEHSDF with pancreatic lipase (PL) and bile salts (BS) that were involved in lipid digestion. 1D/2D NMR spectra indicated that the main chain of LEHSDF consisted of (1 → 2,4)-linked β-D-arabinopyranosyl, (1 → 3)-linked α-L-rhamnopyranosyl, (1 → 4)-linked β-D-xylopyranosyl, (1 → 6)-linked and (1 → 4)-linked β-D-glucopyranosyl, with β-D-galactopyranosyl and α-D-mannopyranosyl as terminal unit. Oil red O staining results suggested that LEHSDF had an effective inhibitory effect on lipid accumulation in HepG2 cells. Isothermal titration calorimetry, fluorescence and circular dichroism spectra showed that BS did not specifically bind to LEHSDF, and the strong inhibitory effect of LEHSDF on lipase was dominated by hydrophobic forces, electrostatic forces, encapsulation and adsorption interactions. The results will be helpful for the design of food containing LEHSDF as a functional additive to control lipid digestion. [ABSTRACT FROM AUTHOR]

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

Pancreatic lipase (PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae (FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL (IC 50 < 10 μmol·L−1). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate (4-MUO) hydrolysis, with the K i values of 1.61, 3.77 and 10.16 μmol·L−1, respectively. Furthermore, docking simulations indicated that two chalcones (isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors. [ABSTRACT FROM AUTHOR]

Hyperglycemia and hyperlipidemia have been symptoms of many serious diseases such as diabetes and atherosclerosis overall the world. Thus, drug researchers have focused on new, natural and healthy drug alternatives. Marine macroalgae is a great source of hypoglycemic, hypolipidemic or hypocholesterolemic agents. In this study, we investigated that hypoglycemic, hypolipidemic and cytotoxic potentials of 22 marine macroalgae from the Gulf of Izmir. According to our results, the cold methanol extract of Polysiphonia denudata exhibited the highest antioxidant activity (93.6%) compared to BHA (95.3%). Three Cystoseira species, Cystoseria crinita (91.9%), Cystoseria barbata (90.7%), Cystoseria compressa (89.8%) showed higher a-glucosidase inhibition rates than oral antidiabetic acarbose (79.5%). It has also been observed that same species are potent inhibitors of pancreatic lipase. Cytotoxicity test revealed that these extracts did not cause viability inhibition on MCF-7. The results of maltose- glucose assay indirectly displayed that Cystoseira cold methanolic extracts inhibited maltose consumption better than acarbose on HT29. The results of this screening study show that these Cystoseira species may provide non- toxic bioactive agents to control non-communicable diseases (NCDs) such as cardiovascular disease and diabetes mellitus. [ABSTRACT FROM AUTHOR]

Molecular weights of trypsin, chymotrypsin, and lipase from anterior intestine and pyloric caeca of Totoaba macdonaldi were evaluated, as well as optimum temperature and pH for activity of the proteases. Trypsin was 24.1 kDa and effectively hydrolyzed Nα-benzoyl-DL-arginine 4-nitroanilide hydrochloride at optimum pH and temperature of 8 and 65°C, respectively. Chymotrypsin was 25.9 kDa and showed higher hydrolytic activity for N-benzoyl-L-tyrosine ethyl ester at pH 8 and 45°C, with a wider range of statistically similar activity values. Two pancreatic lipases of 70.2 and 47.5 kDa were detected, which could be the uncleaved and the final form of a colipase-dependent pancreatic lipase, since enzyme activity was detected without supplementation of bile salts and supplementing them inhibited activity. [ABSTRACT FROM AUTHOR]

Background: The growing incidence of obesity has attracted the concern of researchers to look for effective interventions for its management. Garcinia indica is a widely known ethnomedicine used to treat gastritis, diabetes, and metabolic disorders. Recently, there has been a surge in the use of G. indica fruits in weight loss preparations. Objective: To explore the anti-obesity effect of polyphenol-enriched fraction and the compounds isolated from G. indica fruits through the inhibition of key metabolizing enzymes and oxidative stress. Materials and Methods: Fruits of G. indica were extracted with methanol that was subjected to liquid–liquid extraction to yield ethyl acetate fraction (FGIEF), chloroform, butanol, and aqueous fractions. The extract and the fractions were screened for the total polyphenols content (TPC), total flavonoids content (TFC), pancreatic lipase (PL) and α-amylase inhibition, and antioxidant activity. The effect of FGIEF on the viability of 3T3-L1 preadipocytes using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay was assessed. FGIEF was subjected to normal-phase medium-pressure liquid chromatography (MPLC) to isolate compounds 1–3. Docking studies of representative polyphenols and the isolated compounds 1–3 with PL were undertaken to derive supporting evidence. Results: Among all the fractions, FGIEF was found to have the highest TPC (375.6 ± 4.5 gallic acid equivalent mg/g) and TFC (237.2 ± 6.2 quercetin equivalent mg/g). The extract and fractions showed concentration-dependent digestive enzyme inhibition and antioxidant effect. FGIEF inhibited PL and α-amylase (IC50values 257.3 ± 3.7 and 349.7 ± 5.8 μg/mL, respectively). FGIEF did not induce any cell death up to 800 μg/mL. MPLC of FGIEF led to the isolation of luteolin (1), napthyldioxolol (2), and oleantrienoic acid glucoside (3). Preferential inhibition by polyphenols compared to other compounds was notable in the docking studies. Conclusion: The study suggests that the fruits of G. indica exhibit anti-obesity effect through the inhibition of digestive enzymes that can be mainly attributed to the presence of polyphenols. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Herbal medicines are frequently used for the prevention and treatment of obesity and obesity-related disorders. Our preliminary screening showed that St. John's Wort (SJW) displayed potent inhibition on pancreatic lipase (PL), a key hydrolase responsible for lipid digestion and absorption in mammals. Herein, the inhibition potentials and inhibitory mechanism of SJW extract and its major constituents on PL were fully investigated by a set of in vitro and in silico studies. The results clearly demonstrated that the naphthodianthrones, biflavones and most of flavonoids in SJW displayed strong to moderate inhibition on PL. Among all tested natural compounds, two naphthodianthrones (hypericin and pseudohypericin) and one biflavone (I3,II8-biapigenin) isolated from SJW exhibited potent PL inhibition activity, with the IC 50 values of <1 μM. Inhibition kinetics analyses showed that hypericin, pseudohypericin and I3,II8-biapigenin inhibited PL via a mixed manner, while molecular dynamics simulations revealed that three newly identified PL inhibitors could bind on PL at both the catalytic cavity and the interface between colipase and the C-terminal domain of PL. Collectively, our findings suggested that part of major constituents in SJW displayed potent PL inhibition activities, which could be used as lead compounds for the development of novel PL inhibitors. • The inhibitory effects of St. John's wort extract and its major constituents on pancreatic lipase (PL) are assayed. • Hypericin, pseudohypericin and I3,II8-biapigenin display potent inhibition on PL, with the IC 50 values of <1 μM. • Hypericin, pseudohypericin and I3,II8-biapigenin are mixed inhibitors of PL. • Hypericin, pseudohypericin and I3,II8-biapigeninc could bind on PL at two distinct ligand-binding sites. [ABSTRACT FROM AUTHOR]