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It is difficult to screen out as many active components as possible from natural plants all at one time. In this study, subfractions of Forsythia suspensa leaves were firstly prepared; then, their inhibitive abilities on pancreatic lipase were tested; finally, the highest inhibiting subfraction was screened by self-made immobilized pancreatic lipase. Results showed that nine ligands, including eight inhibitors and one promotor, were screened out all at one time. They were three flavonoids (rutin, IC50: 149 ± 6.0 μmol/L; hesperidin, 52.4 μmol/L; kaempferol-3-O-rutinoside, isolated from F. suspensa leaves for the first time, IC50 notably reached 2.9 ± 0.5 μmol/L), two polyphenols (chlorogenic acid, 3150 ± 120 μmol/L; caffeic acid, 1394 ± 52 μmol/L), two lignans (phillyrin, promoter; arctigenin, 2129 ± 10.5 μmol/L), and two phenethyl alcohol (forsythiaside A, 2155 ± 8.5 μmol/L; its isomer). Their action mechanisms included competitive inhibition, competitive promotion, noncompetitive inhibition, and uncompetitive inhibition. In sum, using the appropriate methods, more active ingredients can be simply and quickly screened out all at one time from a complex natural product system. In addition, F. suspensa leaves contain numerous inhibitors of pancreatic lipase.

Inhibition of human pancreatic lipase, a crucial enzyme in dietary fat digestion and absorption, is a potent therapeutic approach for obesity treatment. In this study, human pancreatic lipase inhibitory activity of aurone derivatives was explored by molecular modeling approaches. The target protein was human pancreatic lipase (PDB ID: 1LPB). The 3D structures of 82 published bioactive aurone derivatives were docked successfully into the protein catalytic active site, using AutoDock Vina 1.5.7.rc1. Of them, 62 compounds interacted with the key residues of catalytic trial Ser152-Asp176-His263. The top hit compound (A14), with a docking score of −10.6 kcal⋅mol−1, was subsequently submitted to molecular dynamics simulations, using GROMACS 2018.01. Molecular dynamics simulation results showed that A14 formed a stable complex with 1LPB protein via hydrogen bonds with important residues in regulating enzyme activity (Ser152 and Phe77). Compound A14 showed high potency for further studies, such as the synthesis, in vitro and in vivo tests for pancreatic lipase inhibitory activity.

As for ligand fishing, the current immobilization approaches have some potential drawbacks such as the small protein loading capacity and difficult recycle process. The core–shell metal–organic frameworks composite (Fe3O4-COOH@UiO-66-NH2), which exhibited both magnetic characteristics and large specific surface area, was herein fabricated and used as magnetic support for the covalent immobilization of porcine pancreatic lipase (PPL). The resultant composite Fe3O4-COOH@UiO-66-NH2@PPL manifested a high loading capacity (247.8 mg/g) and relative activity recovery (101.5%). In addition, PPL exhibited enhanced tolerance to temperature and pH after immobilization. Then, the composite Fe3O4-COOH@UiO-66-NH2@PPL was incubated with the extract of Scutellaria baicalensis to fish out the ligands. Eight lipase inhibitors were obtained and identified by UPLC-Q-TOF-MS/MS. The feasibility of the method was further confirmed through an in vitro inhibitory assay and molecular docking. The proposed ligand fishing technique based on Fe3O4-COOH@UiO-66-NH2@PPL provided a feasible, selective, and effective platform for discovering enzyme inhibitors from natural products.

Pancreatic lipase catalyzes the cleavage of triacylglycerols at the oil–water interface, and is known as the dominant determiner of dietary fat digestion. Reducing dietary fat digestion and absorption by modulating the activity of pancreatic lipase has become a favorable strategy to tackle obesity. Orlistat is, at present, the only pancreatic lipase inhibitor approved for the treatment of obesity; however, an array of gastrointestinal adverse effects associated with orlistat limits its tolerability. As a safe alternative to orlistat, a number of natural product-derived compounds with varying degrees of pancreatic lipase inhibitory activity have been reported. We herein reported that bioactivity-guided fractionation of sesame meal led to the identification of free linoleic acid and oleic acid as potent inhibitors of porcine pancreatic lipase in vitro with an IC50 of 23.1 µg/mL (82.4 µM) and 11.7 µg/mL (41.4 µM), respectively. In rats, a single oral dose of the mixture of these fatty acids significantly suppressed the elevation of blood triacylglycerol level following fat intake. These results substantiate the role of free linoleic acid and oleic acid as a novel class of natural product-derived functional molecules that act as pancreatic lipase inhibitors, and their potential for healthy, routine-based weight management.

The rising global incidence of obesity underscores the urgent demand for effective therapeutic interventions. Natural products have emerged as promising alternatives; however, identifying candidates that effectively target the complex mechanisms underlying obesity remains a critical challenge. In this study, the specialized metabolites of Dendrobium albosanguineum were investigated for their anti-obesity potential. Methanolic extraction was performed on the entire plant, followed by systematic fractionation and compound elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy. A set of in vitro colorimetric assays was employed to assess pancreatic lipase inhibition, cytotoxicity, intracellular lipid storage, triglyceride content, and glycerol release in murine (3T3-L1) and/or human (PCS-210-010) adipocyte models. In addition, flow cytometry, western blotting analysis, and RT-qPCR were used to evaluate the effects of a chosen metabolite on cell cycle progression and the expression of adipogenesis-related genes and proteins. Eight metabolites were isolated, including bibenzyls (moscatilin, chrysotoxine), lignans (syringaresinol, foliachinenoside C), a sterol (daucosterol), a phenylpropanoid ( n -octacosyl- trans - p -coumarate), and flavonoids (rhoifolin, kaempferol-3- O -(2″,6″-dirhamnosyl)glucoside). Among them, foliachinenoside C exhibited the most potent activity, with 94.77 ± 0.85% inhibition of pancreatic lipase (IC 50  = 40.73 ± 0.74 µM). It significantly reduced triglyceride levels and promoted glycerol release in both murine and human adipocytes. Mechanistically, foliachinenoside C induced cell cycle arrest at the G0 phase in 3T3-L1 cells and downregulated key adipogenic transcription factors (PPARγ, C/EBPα, SREBP1c) and lipogenic proteins (FAS, PLIN1, LPL, ADPN, FABP4). Moreover, it modulated the AKT/GSK3β and AMPK-ACC signaling pathways, collectively suppressing adipocyte differentiation. These findings position foliachinenoside C as a promising plant-derived compound for obesity pharmacotherapy, warranting further investigation to facilitate its clinical development.

Three new tetradentate NNNS Schiff bases (L1–L3) derived from 2-(piperidin-4-yl)ethanamine were prepared in high yields. UV–Visible and FTIR spectroscopy were used to monitor the dehydration reaction between 2-(piperidin-4-yl)ethanamine and the corresponding aldehydes. Structures of the derived Schiff bases were deduced by 1H and 13C NMR, FTIR, UV–Vis, MS, EA, EDS, and TG-derived physical measurements. DFT/B3LYP theoretical calculations for optimization, TD-DFT, frequency, Molecular Electrostatic Potential (MEP), and highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) / were performed for L2. The in vitro antimicrobial activities of the three Schiff bases were evaluated against several types of bacteria by disk diffusion test using Gentamicin as the standard antibiotic. Schiff bases revealed good antioxidant activity by the DPPH method, and the IC50 values were compared to the Trolox standard. Pancreatic porcine lipase inhibition assay of the synthesized compounds revealed promising activity as compared to the Orlistat reference.

A great number of chemically diverse pancreatic lipase (PL) inhibitors have been identified to tackle obesity; however, very few of them have entered clinical studies. The ethanolic extract of sesame meal is a potent PL inhibitor, and its activity hinges exclusively on two free fatty acids: linoleic acid and oleic acid, which were proven to reduce postprandial triglyceride excursion in rats. Herein, to investigate the clinical efficacy of the sesame meal extract, in a crossover trial, 30 healthy volunteers were randomized to receive the sesame meal extract containing experimental food or placebo along with a high-fat meal. Treatment with the sesame meal extract significantly lowered the incremental postprandial serum triglyceride concentration and reduced the incremental area under the curve (iAUC) by 16.8% (p-value = 0.03) compared to placebo. Significant decreases in postprandial remnant-like lipoprotein particle cholesterol and low-density lipoprotein particles were also observed, whereas high-density lipoprotein cholesterol was increased. These results suggest that treatment with the sesame meal extract significantly reduced the postprandial excursion of triglycerides and improved the lipidemic profile after high dietary fat intake in healthy individuals, indicating the substantial potential of free linoleic acid and oleic acid and natural products rich in these compounds for the management of obesity and related conditions.

Enzymatic inhibitions of crude extracts and their constituents from Zingiberaceae against both rat intestinal α-glucosidase and porcine pancreatic lipase were investigated. Structure–activity relationships using their derivatives were also investigated. The rhizomes extract of mango ginger, Curcuma amada showed remarkable inhibitory activity in the screening test. Two natural labdane diterpenes 1 and 2 and a drimane sesquiterpene 3 were major constituents isolated from this hexane extract. Among them, (E)-labda-8(17),12-diene-15,16-dial (1) was the most prominent compound and showed inhibitory activity against both α-glucosidase and lipase. Derivatives 4–10 from compound 1 were prepared and evaluated using inhibitory assays with these enzymes. The reduced derivative 4 maintained α-glucosidase inhibitory activity, but had decreased pancreatic lipase inhibitory activity compared with parent compound 1. Other tested derivatives of compound 1, including acetates 5–7 and oxidative derivatives 8–10, had very weak α-glucosidase inhibitory activity. Most of these compounds showed moderate pancreatic lipase inhibitory activity. However, only sesquiterpene albicanal (3) showed drastically decreased pancreatic lipase activity compared with 1. These findings suggested that molecular size was essential for enzymatic inhibitory activities of these compounds. These results demonstrated that mango ginger may be useful for the prevention of obesity and being overweight.

Background Obesity and its related diseases are increasing worldwide. One of the best therapeutic strategies for obesity management is through the inhibition of pancreatic lipase (PL) enzyme. So far orlistat is the only FDA approved PL inhibitor, but with unpleasant side effects. New efficacious anti-obesity drugs are needed to achieve a successful reduction in the incidence and prevalence of obesity. Many microbial metabolites have PL inhibitory activity. Screening soil inhabitants for PL inhibitors could help in increasing the available anti-obesity drugs. We aimed to isolate and identify alternative PL inhibitors from soil flora. Results We screened the crude mycelial methanolic extracts of 39 soil samples for PL inhibitory activity by the quantitative lipase colorimetric assay, using the substrate p -nitrophenyl palmitate and orlistat as positive control. AspsarO, a PL inhibitor producer, was isolated from an agricultural field soil in Giza, Egypt. It was identified as Aspergillus oryzae using colony morphology, microscopical characteristics, 18S rDNA sequencing, and molecular phylogeny. Increasing the PL inhibitor activity, in AspsarO cultures, from 25.9 ± 2% to 61.4 ± 1.8% was achieved by optimizing the fermentation process using a Placket–Burman design. The dried 100% methanolic fraction of the AspsarO culture had an IC 50 of 7.48 μg/ml compared to 3.72 μg/ml for orlistat. It decreased the percent weight gain, significantly reduced the food intake and serum triglycerides levels in high-fat diet-fed Sprague–Dawley rats. Kojic acid, the active metabolite, was identified using several biological guided chromatographic and 1 H and 13 C NMR techniques and had an IC 50 of 6.62 μg/ml. Docking pattern attributed this effect to the interaction of kojic acid with the key amino acids (Lys80, Trp252, and Asn84) in PL enzyme binding site. Conclusion Combining the results of the induced obesity animal model, in silico molecular docking and the lipase inhibitory assay, suggests that kojic acid can be a new therapeutic option for obesity management. Besides, it can lower serum triglycerides in obese patients.

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