Mahanine and 8-hydroxymahanimbine: Pancreatic lipase inhibitors with anti-hyperlipidemic effects from Clausena cambodiana leaves

Roots of the herb Panax ginseng are known to contain high levels of bioactive saponins. Here, we isolated saponins from ginseng root powder and studied their inhibitory effect on the absorption of dietary fat in male Balb/c mice. Consumption of ginseng saponins suppressed the expected increase in body weight and plasma triacylglycerols, following a high-fat diet and observed higher intake. Consumption of ginseng saponins had no effect on the concentration of the total plasma cholesterol in both chow and high-fat diets in mice. The mode by which saponins from ginseng inhibit lipid metabolism was assessed as the in vitro inhibition of pancreatic lipase. Ginseng saponin inhibited pancreatic lipase with an apparent IC50 value of 500 mug/mL. Our results suggest that the anti-obesity and hypolipidemic effects of Ginseng in high-fat diet-treated mice were attributed to the isolated saponin fraction. These metabolic effects of the ginseng saponins may be mediated by inhibition of pancreatic lipase activity.

Methyl xestospongoate (MXS), a brominated polyunsaturalted lipid recently isolated from the Chinese marine sponge Xestospongia testudinaria, showed strong in vitro pancreatic lipase (PL) inhibitory activity. Inspired by its promising activity and potential clinical application, a series of shorter or longer‐chain and chlorinated analogs of MXS was prepared and evaluated for PL inhibitory activity. The result of a bioassay indicated that the terminal brominated ones are better than the chlorinated ones on their bioactivity, and 16–20 C‐atoms in the structures of MXS analogs might be optimal for their PL inhibitory activity. The results obtained in the present work are useful for the design of novel pancreatic lipase inhibitors.

Context: Sea cucumbers have been consumed as tonic, food, and nutrition supplements for many years.Objective: The objective of this study is to investigate the antiobesity and lipid-lowering effects of sea cucumber extracts in in vitro and in vivo models and elucidate the mechanism of action of the extracts on obesity and dyslipidemia.Materials and methods: The 60% ethanol extracts from the body walls of 10 different sea cucumbers were investigated for the inhibition of pancreatic lipase (PL) activity in vitro. The optimal active extract (SC-3) was further chemically analyzed by LC-MS and UV. And 0.1% and 0.2% of SC-3 was mixed with a high-fat diet to treat C57/BL6 mice for 6 weeks or 2 weeks as preventive and therapeutic study. The body weight, serum, and liver lipid profile in the mice were investigated.Results: The crude extract of Pearsonothuria graeffei Semper (Holothuriidae) inhibited the PL activity by 36.44% of control at 0.5 μg/mL. SC-3 and echinoside A inhibited PL with an IC50 value at 2.86 μg/mL and 0.76 μM. 0.1% of SC-3 reduced the body weight (23.0 ± 0.62 versus 26.3 ± 0.76 g), the serum TC (2.46 ± 0.04 versus 2.83 ± 0.12 mmol/L), TG (0.19 ± 0.08 versus 0.40 ± 0.03 mmo/L), and LDL-c (0.48 ± 0.02 versus 0.51 ± 0.02 mmol/L), and liver TC (1.19 ± 0.17 versus 1.85 ± 0.13 mmol/mg) and TG (6.18 ± 0.92 versus 10.87 ± 0.97 mmol/mg) contents of the obese C57BL/six mice on a high-fat diet.Discussion and conclusion: Sea cucumber may be used for developing antiobesity and antihyperlipidemia drugs.

BackgroundObesity 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.ResultsWe 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 IC50 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 1H and 13C NMR techniques and had an IC50 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.ConclusionCombining 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.

Background: Curcumin has been recognized for its diverse therapeutic effects. Little is known about the impact of curcumin on pancreatic lipase inhibition. In recent years, researchers have explored curcumin with new and improved properties. This study evaluated a nano-formulation of curcumin using Tween 80 for its inhibitory effect on porcine pancreatic lipase. The nano-formulation demonstrated significant enzyme inhibition in vitro. Materials and Methods: A pancreatic lipase assay was conducted using p-nitrophenol palmitate as a synthetic substrate. To determine the inhibitory activity of pancreatic lipase, samples at a final concentration of 2 µg/mL were pre-incubated with the synthetic substrate. After the in vitro reaction, the inhibition percentage was calculated by measuring enzyme activity (international units). Additionally, the IC50 value of the curcumin nano-formulation was determined and expressed in μg/mL. The effect of pH (ranging from 3.0 to 9.0) on the pancreatic lipase inhibitory activity of the formulation was also examined. Results: At a final concentration of 2 μg/mL, curcumin and its nano-formulation demonstrated pancreatic lipase inhibition of 4.10 ± 2.0% and 82.9 ± 0.43%, respectively. The IC50 value for the nano-formulation was calculated to be 1.05 μg/mL. Additionally, this curcumin nano-formulation inhibited pancreatic lipase in a pH-dependent manner, with pH 8.0 being identified as the most favorable. Conclusion: This study explored the anti-obesity potential of a nanoform of curcumin. Pancreatic lipase is a recognized therapeutic target for the management of obesity. The nano-formulation exhibited notable pancreatic lipase inhibitory activity at a very low concentration, demonstrating its potency. This opens a new avenue for exploring this molecule as an orally active anti-obesity principle. These findings suggest that this curcumin nano-formulation could be a promising candidate for developing an orally active anti-obesity agent.

Design, synthesis, biological evaluation and molecular modelling studies of novel diaryl substituted pyrazolyl thiazolidinediones as potent pancreatic lipase inhibitors

The present study investigated the effects of green coffee bean extract and Theobroma cacao bean extract on pancreatic lipase activity in vitro. Green coffee bean extract produced a J-shaped dose-dependent inhibition of pancreatic lipase with the percentage inhibition of pancreatic lipase ranging from 11.8% to 61.5%. Similar concentrations of Theobroma cacao failed to produce any effect on pancreatic lipase. Non-linear regression analysis revealed that the concentration of green coffee bean extract required to elicit a 50% inhibition of pancreatic lipase activity (IC50) was approximately 43 μM. In conclusion, extracts of green coffee beans but not Theobroma cacao possess potent inhibitory activity against pancreatic lipase. © 2010 The Authors. Journal compilation © 2010 British Nutrition Foundation.

Excessive fat consumption can cause obesity, which is currently one of the global problems, because it can trigger various diseases such as coronary heart disease, diabetes, and so on. Absorption of fat into the body requires pancreatic lipase enzymes, which can be reduced by lipase inhibitors such as orlistat drugs. Previous research has shown that the extract of papaya seed, which contains many flavonoids, was able to inhibit pancreatic lipase. Therefore, the aims of this study are to isolate and identify the flavonoid compounds from papaya seeds that are active as pancreatic lipase inhibitors. Papaya seed powder was extracted using ethanol 70%, followed by isolation using TLC, identification by phytochemical test and UV and IR spectroscopy, while pancreatic lipase inhibitory activity has been done using titrimetric method. To confirm the Inhibitory activity of the predicted flavonoid against the enzyme, also had been done in silico study. The results had shown that there are two types of flavonoid in the ethanol extract of papaya seed, that are active as pancreatic lipase inhibitors. The two flavonoid isolates have inhibition power of 132 and 12 times stronger than orlistat in the same mass. Result of UV-VIS and IR spectrum has shown that both isolates were suspected to have a similar structure to the three flavonoid compounds: epicatechin, catechin or epigallocatechin-3-gallate (EGCG). In silico study, also confirmed that each of the predicted flavonoids has higher binding affinity against pancreatic lipase, than orlistat.

The inhibition of pancreatic lipase activity to reduce dietary lipid absorption is an effective strategy to combat obesity. Mangiferin, a bioactive flavonoid derived from Mangifera indica, exhibits potent lipid-lowering potential. However, although its in vitro inhibitory effect on pancreatic lipase has been identified, the underlying mechanism remains poorly understood. Direct in vivo evidence of its impact on dietary lipid absorption is also lacking. This study aimed to elucidate the mechanism of mangiferin's inhibition of pancreatic lipase through in vitro inhibitory kinetics assays and in silico molecular docking analysis. Its effects on dietary lipid absorption were also evaluated in a mouse model of high-fat diet (HFD)-induced obesity. Inhibitory kinetics assays demonstrated that mangiferin inhibited pancreatic lipase in a reversible, non-competitive manner, with a half- maximal inhibitory concentration (IC50) of 82.31 μmol L-1. Molecular docking showed that mangiferin bound to the enzyme's allosteric site through hydrogen bonds with Glu-188, Arg-191, Gln-22, and Val-21 residues, consistent with non-competitive inhibition. In vivo studies revealed that administration of 200 mg kg-1 body weight of mangiferin alleviated HFD-induced obesity, hepatic steatosis, and hyperlipidemia significantly. Notably, mangiferin increased fecal lipid excretion by 52.5%, which was significant, indicating reduced dietary lipid absorption. These findings suggest that mangiferin is a promising pancreatic lipase inhibitor, which may reduce dietary lipid absorption, contributing, at least partially, to its lipid-lowering effects. © 2025 Society of Chemical Industry.

Interference with fat hydrolysis results in the reduced use of ingested lipids. Inhibition of pancreatic lipase reduces the efficiency of fat absorption in the small intestine and thereby initiates modest long-term reduction in body weight. In an attempt to select peptides with affinity for the surface of pancreatic lipase and potential inhibitory activity, a random, cyclic heptapeptide phage-displayed library was used. Five independent selections, differing in elution step, were performed. In three selection protocols, a sequential elution strategy was applied in anticipation of improving the selection of high-affinity clones. Four heptapeptides with the highest affinity, seemingly for pancreatic lipase, were selected, synthesized, and characterized for their capacity to inhibit enzyme function. Although no clear consensus among the sequenced peptides was found, one of the selected peptides inhibited pancreatic lipase with an apparent inhibition constant of 16 muM.

Pancreatic lipase is one of the most important key targets in the treatment of obesity. Inhibition of pancreatic lipase can effectively reduce lipid absorption and treat obesity and other related metabolic disorders. The goal of this study is the efficient screening of pancreatic lipase inhibitors in the root and rhizome of Rheum palmatum using affinity ultrafiltration-high-performance liquid chromatography (AUF-HPLC) combined with high-resolution inhibition profiling (HRIP). Potential pancreatic lipase ligands and pancreatic lipase inhibitors in ethyl acetate fraction of R. palmatum were screened using AUF-HPLC and HRIP, respectively. All screened compounds were identified by HPLC- quadrupole time-of-flight (Q-TOF)/MS. Eight compounds were screened out by both AUF-HPLC and HRIP, and six compounds were screened out by either AUF-HPLC or HRIP alone. The pancreatic lipase inhibitory activities of all screened compounds were verified by enzyme inhibition assay and molecular docking. Five new potent pancreatic lipase inhibitors were discovered, namely procyanidin B5 3,3'-di-O-gallate (IC50 = 0.06 ± 0.01 μM), 1,6-di-O-galloyl-2-O-cinnamoyl-β-D-glucoside (IC50 = 12.83 ± 0.67 μM), 1-O-(1,3,5-trihydroxy)phenyl-2-O-galloyl-6-O-cinnamoyl-β-D-glucoside (IC50 = 17.84 ± 1.33 μM), 1,2-di-O-galloyl-6-O-cinnamoyl-β-D-glucoside (IC50 = 18.39 ± 1.52 μM), and 4-(4'-hydroxyphenyl)-2-butanone-4'-O-β-D-(2"-O-galloyl-6"-O-cinnamoyl)-glucoside (IC50 = 2.91 ± 0.40 μM). It was found that procyanidin B5 3,3'-di-O-gallate showed higher pancreatic lipase inhibitory activity than the positive control orlistat (IC50 = 0.12 ± 0.02 μM). The combination of affinity ultrafiltration-high-performance liquid chromatography (AUF-HPLC) and high-resolution inhibition profiling (HRIP) could reduce the risk of false-negative screening and missed screening and could achieve more efficient screening of bioactive compounds in complex natural products.

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

The inhibitory activity of Flos Sophorae Immaturus extract and its major flavonoid components on pancreatic lipase

Pancreatic lipase digests dietary fats by hydrolysis, which is a key enzyme for lipid absorption. Therefore, reduction of fat absorption by the inhibition of pancreatic lipase is suggested to be a therapeutic strategy for obesity. From the EtOAc-soluble fraction of the stem barks of Fraxinus rhynchophylla (Oleaceae), four secoiridoids such as ligstroside (1), oleuropein (2), 2″-hydroxyoleuropein (3) and hydroxyframoside B (4) were isolated. The inhibitory activity of these compounds on pancreatic lipase was assessed using porcine pancreatic lipase as an in vitro assay system. Compound 4 showed the strongest inhibition on pancreatic lipase, which followed by compounds 1–3. In addition, compound 4 exerted inhibitory effect on pancreatic lipase in a mixed mechanism of competitive and noncompetitive manner. Taken together, F. rhynchophylla and its constituents might be beneficial to obesity.

QSAR model of pancreatic lipase inhibition by phenolic acids and their derivatives based on machine learning and multi-descriptor strategy