Dietary polyphenols have shown hypolipidemic effects by reducing triglyceride absorption. The mechanisms may involve modifying fat emulsion during digestion in the gastrointestinal tract and suppressing lipase during hydrolysis in the small intestine. In an in vivo study, lotus seedpod oligomeric procyanidin (LSOPC) decreased total serum triglyceride and total cholesterol and elevated the high-density lipoprotein level in the hyperlipidemic rat model. In addition, LSOPC suppressed de novo lipogenesis-related gene expressions. In an in vitro study, the LSOPC-enriched emulsion decreased the mean droplet size from 0.36 to 0.33 μm and increased the viscosity of the emulsion. Moreover, the LSOPC-enriched emulsion improved the antioxidant properties. A digestion model was developed and showed that the particle size of the LSOPC-enriched emulsion increased in the oral cavity. However, an increase and then a significant drop of the particle size was measured in the stomach and small intestine. The free fatty acid release rate was decreased in the LSOPC-enriched emulsion partly ascribed to the inhibition of lipase by LSOPC.

Aim: Due to the pivotal role in the oxidative deamination of monoamine neurotransmitters, two distinct monoamine oxidase (MAO) subtypes, MAO-A and MAO-B, present a significant pharmacological interest. Here, we reported a hierarchical and time-efficient ligand-based virtual screening strategy to identify potent selective and reversible MAO inhibitors. Result: A total of 130 compounds were assessed in dose-response biochemical assay against MAOs. Among them, 70 compounds were active with inhibition higher than 70%, involving 25 compounds with IC50 values less than 1 mu M. Conclusion: Our research demonstrated the validity of Biologically Relevant Spectrum (BRS-3D) in predicting subtype-selective ligands and afforded a novel highly efficient way to develop selective inhibitors in the early stage of drug discovery.

As a major component of green tea, (-)-epigallocatechin-3-gallate (EGCG) has attracted interest from scientists owing to its potential to combat a variety of human diseases including abnormal glucose metabolism in obesity and diabetes. This study aims to (1) evaluate the molecular mechanism of EGCG in starch digestion before EGCG absorption; (2) investigate the link between PXR/CAR-mediated phase II metabolism and glucose homeostasis after EGCG is transported to small intestine and liver. EGCG suppressed starch hydrolysis both in vitro and in vivo. Molecular simulation results demonstrated that EGCG could bind to the active site of α-amylase and α-glucosidase, acting as an inhibitor. In addition, the anti-diabetic action of EGCG was investigated in high fat diet and STZ-induced type 2 diabetes. EGCG improved glucose homeostasis and inhibited the process of gluconeogenesis (PEPCK and G-6-Pase) and lipogenesis (SREBP-1C, FAS and ACC1) in the liver. Meanwhile, EGCG treatment activated PXR/CAR, accompanied by upgrading PXR/CAR-mediated phase II drug metabolism enzyme expression in small intestine and liver, involving SULT1A1, UGT1A1 and SULT2B1b. Dietary polyphenol EGCG could serve as a promising PXR/CAR activator and therapeutic intervention in diabetes.

Menaquinone (MK) has an important role in human metabolism as an essential vitamin (VK2), which is mainly produced through the fermentation of microorganisms. MK8(H2) was identified to be the main menaquinone from Rhodococcus sp. B7740, a bacterium isolated from the arctic ocean. In this work, MK8(H2) (purity: 99.75%) was collected through a convenient and economic extraction process followed by high-speed countercurrent chromatography (HSCCC) purification. Additionally, high-resolution mass spectrometry (HRMS) was performed for further identification and the hydrogenation position of MK8(H2) (terminal unit) was determined using nuclear magnetic resonance (NMR) for the first time. MK8(H2) showed a superior antioxidant effect and antiglycation capacity compared with ubiquinone Q10 and MK4. High-performance liquid chromatography–mass spectrometer (HPLC-MS/MS) and molecular docking showed the fine interaction between MK8(H2) with methylglyoxal (MGO) and bull serum albumin (BSA), respectively. These properties make MK8(H2) a promising natural active ingredient with future food and medicine applications.

Off-target effects played a vital role in the pharmacological understanding of drug efficacy and this research aimed to use text mining strategy to curate molecular level information and unveil the mechanism of off-target effect caused by the usage of anti-multiple myeloma (MM) drugs. After training a hybrid CNN-CRF-LSTM neural network upon the training data from TAC 2017 benchmark database, we extracted all of the side effects of 16 anti-MM drugs from drug labels, and combined the results with existed database. Afterwards, gene targets of anti-MM drugs were obtained by using structure similarity, and their related phenotypes were retrieved from Human Phenotype Ontology. Furthermore, linked phenotypes to candidate genes and adverse reaction of known drugs formed a knowledge graph. Through regulation analysis upon intersected phenotypes of drugs and target genes, an off-target effect caused by SLC7A7 was found, which with high possibility unveiled the pharmacological mechanism of side effect after using combination of anti-MM drugs.

To monitor the abuse of antibacterial synergists, a hapten, trimethoprim carboxylic derivative (TMPCOOH), was designed by using molecular modelling technology. A broad-spectrum monoclonal antibody (mAb) TMP/2G1 was prepared, for which the IC50 values of trimethoprim, diaveridine, aditoprim, baquiloprim, ormetoprim, and brodimoprim were 0.232, 0.527, 1.479, 4.354, 0.965, and 0.119 mu g L-1, respectively. Based on the broad spectrum mAb, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was developed to determine the residues of antibacterial synergists. The limit of detection regarding the developed ic-ELISA for antibacterial synergists ranged from 0.025 to 1.126 mu g L-1 in milk, honey and edible animal tissues. The recoveries ranged from 81.4% to 107.7%, with a coefficient of variation less than 20%. A good correlation (R-2 = 0.994) between the ic-ELISA and HPLC-MS/MS showed the reliability of the developed ic-ELISA.

Isorenierantene was reported to be an aromatic carotenoid and has become a food ingredient, mainly from smear cheese, which possesses special antioxidant ability and significant photoprotective effect. In this paper, the interaction of isorenieratene with human serum albumin (HSA) was explored and compared with that of nonaromatic carotenoids using multi-spectroscopic methods and docking simulations. The results suggested isorenieratene could bind to HSA through a static quenching mechanism. The binding processes were spontaneous and exothermic, and the binding between isorenieratene and HSA was mainly driven by hydrophobic forces and electrostatic attraction. Synchronous fluorescence spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and surface-enhanced Raman scattering (SERS) experiments showed isorenieratene may change the secondary structure of HSA and the micro-environment of its amino acids. Additionally, isorenieratene showed higher stability during the binding process than did nonaromatic carotenoids. Docking simulation indicated isorenieratene may bind to HSA at site II.