Identification of pancreatic lipase inhibitors from Eucommia ulmoides tea by affinity-ultrafiltration combined UPLC-Orbitrap MS and in vitro validation

Huang, Han; Han, Ming; Gu, Qi; Wang, Jiandong; Zhao, Heng; Zhai, Bo-Wen; Nie, Shuai; Liu, Zhiguo; Fu, Yujie

doi:10.1016/j.foodchem.2023.136630

Cited by 7 publications

(1 citation statement)

References 37 publications

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“…However, peptides incorporating β-amino acids have been reported as anti-HIV [ 35 ], anti-cancer [ 36 ], antimicrobial [ 37 ], and anti-bacterial [ 38 ]. Recently, plant sources [ 39 , 40 ] have been extensively studied as PL inhibitors. In addition, synthetic PL-inhibiting molecules like thiazole–benzimidazole conjugates [ 41 ], quinazolinone hybrid analogs [ 42 ], coumarin derivatives [ 43 ], indole–thiazolidinedione hybrids [ 44 ], and salicylanilides [ 45 ] have also been reported.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Short α and β-Mixed Peptides with Excellent Anti-Lipase Activities

Ahmed,

Asif,

Arfan

et al. 2024

Molecules

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Obesity is a source of significant pathologies and deadly diseases, including heart disease, diabetes, and cancer. One of the most intriguing strategies in the hunt for new anti-obesity medications is the inhibition of pancreatic lipase (PL). This study presents a novel application of short α and β-mixed peptides as pancreatic lipase inhibitors. These peptides were synthesized in the solution phase and characterized using FTIR and 1H-NMR. L-proline is present in a high percentage of natural anti-lipase peptides and was used as a β-amino acid in this study to enhance anti-lipase activity and proteolytic stability. Moreover, L-α-proline was converted to β-amino acid derivatives using the Arndt–Eistert method with the advantage of stereo control at the α-carbon. The synthesized peptides with anti-lipase activity are N-Boc-β-Pro-Gly-OBz (93%), N-Boc-O-Bz-Tyr-β-Pro-β-Pro-Gly-OBz (92%), N-Boc-O-Bz-Tyr-β-Pro-COOH (91%), N-Boc-Phe-β-Pro-OCH3 (90%), and N-Boc-O-Bz-Tyr-β-Pro-OCH3 (89%). These peptides may function as lead molecules for further modification to more significant molecules, which can help control obesity.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Short α and β-Mixed Peptides with Excellent Anti-Lipase Activities

Ahmed,

Asif,

Arfan

et al. 2024

Molecules

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Quaternity method for integrated screening, separation, extraction optimization, and bioactivity evaluation of acetylcholinesterase inhibitors from Sophora flavescens Aiton

Zhang,

et al. 2024

Phytochemical Analysis

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IntroductionSophora flavescens Aiton (Fabaceae), a ubiquitous plant species in Asia, contains a wide range of pharmacologically active compounds, such as flavonoids, with potential anti‐Alzheimer's disease (anti‐AD) effects.ObjectivesThe objective of the study is to develop a quaternity method for the screening, isolation, extraction optimization, and activity evaluation of acetylcholinesterase (AChE)‐inhibiting compounds from S. flavescens to realize high‐throughput screening of active substances in traditional Chinese medicine and to provide experimental data for the development of anti‐AD drugs.MethodsWith AChE as the target molecule, affinity ultrafiltration and liquid chromatography‐mass spectrometry were applied to screen for potential inhibitors of the enzyme in S. flavescens. Orthogonal array experiments combined with the multi‐objective Non‐Dominated Sorting Genetic Algorithm III was used for the first time to optimize the process for extracting the active substances. Enzyme inhibition kinetics and molecular docking studies were performed to verify the potential anti‐AD effects of the active compounds.ResultsFive AChE‐inhibiting compounds were identified: kushenol I, kurarinone, sophoraflavanone G, isokurarinone, and kushenol E. These were successfully separated at purities of 72.88%, 98.55%, 96.86%, 96.74%, and 95.84%, respectively, using the n‐hexane/ethyl acetate/methanol/water (4.0/5.0/4.0/5.0, v/v/v/v), n‐hexane/ethyl acetate/methanol/water (5.0/5.0/6.0/4.0, v/v/v/v), and n‐hexane/ethyl acetate/methanol/water (4.9/5.1/5.7/4.3, v/v/v/v) mobile phase systems. Enzyme inhibition kinetics revealed that kushenol E had the best inhibitory effect.ConclusionThis study elucidates the mechanism of action of five active AChE inhibitors in S. flavescens and provides a theoretical basis for the screening and development of anti‐AD and other therapeutic drugs.

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Rapidly screening of pancreatic lipase inhibitors from Clematis tangutica using affinity ultrafiltration‐HPLC‐QTOFMS technique combined with targeted separation, in vitro validation, and molecular docking

Wei,

Chen,

Song

et al. 2024

Phytochemical Analysis

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IntroductionScreening of novel pancreatic lipase inhibitors from complex natural products is a meaningful task.ObjectivesThrough accurately screening and separating pancreatic lipase inhibitors from Clematis tangutica (C. tangutica), to discover new leading compounds for slimming and accelerate the development and utilization of Tibetan medicine resources.MethodsAn integrated strategy that combines affinity ultrafiltration and high‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (AU‐HPLC‐QTOFMS), targeted separation, in vitro validation, and molecular docking was developed to screen pancreatic lipase inhibitors from C. tangutica. The AU‐HPLC‐QTOFMS technique was performed to fish for the potential active substances. Macroporous resin, preparative liquid chromatography, and high‐speed countercurrent chromatography were implemented for the accurate and targeted separation of active compounds. The inhibitory activities of target compounds to pancreatic lipase were detected by the inhibition experiments in vitro. The binding affinities and binding sites were analyzed using molecular docking.ResultsA total of eleven kinds of pancreatic lipase inhibitory substances were screened from C. tangutica. Seven triterpenoid saponins were screened for the first time as lipase inhibitors and successfully prepared with purities higher than 97%. Tanguticoside B, clematangoticoside J, hederoside H1, and rutin showed stronger inhibitory effects with IC50 values of 1.539 ± 0.048, 1.661 ± 0.092, 1.793 ± 0.069, and 1.792 ± 0.094 mmol/l. Moreover, they have the lowest ΔG values of −10.84, −9.97, −10.87, and −9.39 kcal/mol to pancreatic lipase.ConclusionThe integrated strategy using AU‐HPLC‐QTOFMS, targeted separation, in vitro validation, and molecular docking was feasible for rapidly screening and directionally isolating pancreatic lipase inhibitors from C. tangutica.

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Identification of pancreatic lipase inhibitors from Eucommia ulmoides tea by affinity-ultrafiltration combined UPLC-Orbitrap MS and in vitro validation

Cited by 7 publications

References 37 publications

Synthesis and Characterization of Short α and β-Mixed Peptides with Excellent Anti-Lipase Activities

Synthesis and Characterization of Short α and β-Mixed Peptides with Excellent Anti-Lipase Activities

Quaternity method for integrated screening, separation, extraction optimization, and bioactivity evaluation of acetylcholinesterase inhibitors from Sophora flavescens Aiton

Rapidly screening of pancreatic lipase inhibitors from Clematis tangutica using affinity ultrafiltration‐HPLC‐QTOFMS technique combined with targeted separation, in vitro validation, and molecular docking

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