A new efficient multi-stage strategy based on the complementarity of ultrafiltration and high resolution biochromatogram for the screening of skin-whitening candidates from the fibrous root of Bletilla striata

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IntroductionPancreatic 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.ObjectivesThe 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).MethodsPotential 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.ResultsFive 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).ConclusionThe 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.

Section: Introductionmentioning

confidence: 99%

“…HRIP can avoid false‐positive screening to a large extent 29 . However, it can easily lead to false‐negative screening of trace bioactive compounds in complex mixtures 29 …”

Section: Introductionmentioning

confidence: 99%

Efficient screening of pancreatic lipase inhibitors from Rheum palmatum by affinity ultrafiltration–high‐performance liquid chromatography combined with high‐resolution inhibition profiling

Quan,

Wen,

et al. 2023

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Comparative study on metabolite variations of two rose teas by plant metabolomics and revealing their skin‐whitening candidates by spectrum–effect relationship analysis

Xu,

Ye,

Zhang

et al. 2024

IntroductionRosa rugosa var. plena Rehd (CBR) and Rosa chinensis cv. “JinBian” (JBR) are two common species used in rose tea among different original species. CBR, the officially documented original plant of the rose species for food and medicinal purposes, is more costly than JBR. With increasing demand for different rose teas, it is meaningful to compare the chemical constituents for their quality control and reveal their skin‐whitening components that will provide in‐depth insights for the expansion of the rose tea industry.ObjectiveThis study aims to reveal the chemical variances between CBR and JBR and determine their skin‐whitening components.MethodologyA strategy obtained by combining MS‐based plant‐metabolomics with spectrum–effect relationship analysis has been proposed for unveiling chemical differences between CBR and JBR and further exploring their potential skin‐whitening components.ResultsA total of 2030 metabolites were found that revealed considerable differences between CBR and JBR. The results of bioactivity assay demonstrated that JBR exhibited stronger tyrosinase inhibition activity than CBR. Six potential skin‐whitening compounds (di‐O‐galloyl‐HHDP‐glucoside, tri‐O‐galloyl‐HHDP‐glucoside, spiraeoside, quinic acid, rugosin A, and 1,2,3,6‐tetra‐O‐galloyl‐glucose) were discovered as potential tyrosinase inhibitors, via spectrum–effect relationship analysis. This is the first time that di‐O‐galloyl‐HHDP‐glucoside, tri‐O‐galloyl‐HHDP‐glucoside, rugosin A, and 1,2,3,6‐tetra‐O‐galloyl‐glucose have been reported with tyrosinase inhibitory activity. Additionally, molecular docking analysis was used to reveal the inhibition mechanism of these compounds toward tyrosinase.ConclusionThe finding of this study will be of great importance for the quality control of the two types of rose teas, and the revealed active ingredients will provide in‐depth insights for the expansion of the rose tea industry.

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

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.