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One of the most effective therapeutic proposals for type 2 diabetes mellitus (T2DM) is regulation of postprandial blood glucose (PBG) level by inhibiting α-glucosidases. In this study, we firstly investigated the influence of ginsenoside Rg1 (Rg1) on activity of α-glucosidase in vitro. The results revealed that Rg1 had a reversible inhibition on α-glucosidase activity in an uncompetitive manner. Fluorescence spectrum and circular dichroism (CD) analysis indicated that the stable complex between Rg1 and α-glucosidase was mainly formed by hydrogen bonds and hydrophobic forces. In addition, the anti-hyperglycemic effect of Rg1 was confirmed by the sucrose tolerance test in normal and db/db mice. Caco-2 monolayer cell model further emphasized that decreasing effect of Rg1 on PBG may be achieved by reducing glucose uptake and transport which is accounted for inhibition of α-glucosidase. Taken together, those results suggested that Rg1 may be used as a promising α-glucosidase inhibitor to decrease PBG.

The fine aggregate of siliceous rock has the advantages of high production efficiency, stable yield and low construction and transportation cost. The Yangxi concrete dam was firstly apply siliceous rock as fine aggregate to a large concrete project of three million m3. However, siliceous rock aggregate has high SiO2 content, which is easy to trigger alkali-silicate reactivity. To investigate the alkali-silica reactivity characteristics of siliceous rock fine aggregate and its inhibitory measures, in this work, we used fly ash, ordinary silicate cement, and siliceous rock fine aggregate to prepare cement mortar. The effects of fly ash admixture on the expansion rate, as well as the flexural and compressive strength of the mortar were investigated by the mortar rod rapid method and mechanical tests. The inhibition mechanism of fly ash on the siliceous rock fine aggregate was analyzed by scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) techniques. The results showed that the addition of 30 % fly ash to the siliceous rock mortar could effectively limit the mortar expansion and its late strength growth was the most rapid. Compared to siliceous rock mortar without fly ash, the FA30 specimen mixed with 30 % fly ash had a denser structure, the hydration products at the ITZ were more closely arranged, and the C-A-S-H gel with a low calcium-silica ratio was generated internally, which could effectively inhibit the ASR of the siliceous rock fine aggregate.

Tyrosinase is a rate-limiting enzyme for melanogenesis and abnormal melanin production can be controlled by utilizing tyrosinase inhibitory substances. To develop potent and safe inhibitors of tyrosinase, complex tannins a narrowly distributed plant polyphenols were prepared from the fruit peel of Euryale ferox (EPTs) and then structurally characterized, as well as investigated for their inhibitory effects and the involved mechanisms against tyrosinase activity and melanogenesis. The structures of EPTs were established to consist of 63.49% hydrolyzable tannins and 36.51% flavan-3-ol units. EPTs inhibited both the monophenolase and diphenolase activities of tyrosinase efficiently. This outstanding inhibition was presumably ascribed to the strong copper-ion chelating ability of EPTs and the microenvironment modification and secondary structure rearrangement of tyrosinase caused by the formation of EPTs-tyrosinase complexes. Treatment of EPTs to B16F10 cells also decreased the intracellular tyrosinase activity, induced apoptosis and G2/M cell cycle arrest, suppressed melanoma cell proliferation and downregulated the mRNA expression of tyrosinase, TRP-1 and MITF, consequently leading to a distinct reduction in melanin content. Furthermore, EPTs exhibited powerful antioxidant properties, which maybe contributed to impeding the initial steps of melanin formation. This study offered theoretical guidance for the potential applications of EPTs in cosmetic, functional food and medical industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Theaflavins, oxidation product of tea polyphenols, have demonstrated significant inhibitory effects on α-glucosidase, which is beneficial in alleviating hyperglycemia. This study found that the inhibition of four monomers of theaflavins on α-glucosidase was related to the presence of the galloyl moiety (GM), with IC 50 values ranging from TFDG (0.26 mg/mL) < TF3'G (0.33 mg/mL) < TF3G (0.39 mg/mL) ≪ TF (3.26 mg/mL). The multi-spectroscopic analyses revealed that theaflavin monomers changed the microenvironment around aromatic amino acid residues and conformation of α-glucosidase, with the hierarchy being TFDG > TF3'G > TF3G > TF. The binding of theaflavins with α-glucosidase was confirmed by differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC), molecular docking and molecular dynamics simulations analysis. It was confirmed that theaflavins can form stable complexes with α-glucosidase, and that hydrogen bonding and van der Waals forces play important roles in the binding of theaflavins to α-glucosidase. The strongest binding affinity was observed between TFDG and the enzyme's active site, which corresponded with its enzyme activity inhibition ability. The study suggests that GM substitution plays a crucial role in enhancing the binding of theaflavins to α-glucosidase, thereby inducing greater conformational changes and leading to a stronger inhibitory effect on α-glucosidase., Competing Interests: Declaration of competing interest The authors declare that no conflicts of interests exist., (Copyright © 2025 Elsevier B.V. All rights reserved.)

The objective of this study was to investigate the antioxidant mechanism of action of fucoidan in sunflower oil and its oil-in-water emulsion. In addition, the effect of lecithin on the antioxidant mechanism of action of fucoidan in sunflower oil was investigated. In sunflower oil, fucoidan at 0.02 % (w/w) concentration showed the highest induction period (591.02 h), while in sunflower oil-in-water emulsion, fucoidan at 0.04 % (w/w) concentration showed the highest induction period (141.57 h). In addition, the induction period of sunflower oil samples containing fucoidan with lecithin was higher than those without lecithin. Evaluating the mechanism of action of fucoidan in sunflower oil and its oil-in-water emulsion indicated that fucoidan took part in the initiation chain's side reactions and the major termination reaction. The interfacial tensions of samples containing lecithin were significantly lower than those without lecithin. In addition, the reverse micelle size of samples containing lecithin was considerably lower than those without lecithin. Therefore, lecithin enhanced fucoidan's effectiveness by decreasing interfacial activity and increasing the capacity to incorporate lipid hydroperoxides within the structure of reverse micelles. The water produced during oxidation played an essential role in the antioxidant potency of fucoidan. Taken together, lecithin significantly enhanced the antioxidant activity of fucoidan by improving its interfacial activity in sunflower oil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Browning caused by polyphenol oxidase (PPO) and microorganisms significantly impacts the nutritional quality of fruits and vegetables. This study identified 7-(Diethylamino) coumarin-3-carboxylic acid (7-DCCA) as an effective inhibitor of both PPO and bacteria. Enzyme assays revealed that 7-DCCA competitively inhibits PPO activity with an IC 50 value of 0.275 ± 0.002 mM. Fluorescence and molecular simulation methods demonstrated that 7-DCCA forms a complex with PPO through hydrogen bonding and hydrophobic interactions, altering the enzyme's structure and reducing its activity. Thermogravimetric and differential scanning calorimetry (DSC) assays showed that 7-DCCA stabilizes PPO, delaying its thermal decomposition. Antibacterial tests proved that 7-DCCA inhibits Staphylococcus aureus and Escherichia coli by disrupting cell membranes. Additionally, 7-DCCA suppressed PPO and peroxidase activities, delaying phenolic oxidation and preventing browning in fruits and vegetables. Cytotoxicity assays confirmed its safety, with over 85 % cell viability at concentrations up to 0.1 mM. Stability experiments verified that 7-DCCA had greatly light and thermal stability. This study highlighted 7-DCCA as a promising antibrowning agent with potential application in food preservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bisdemethoxycurcumin (BDMC), a demethoxy derivative of curcumin, has garnered interest for its potential anti-tyrosinase properties, which are crucial for applications in food preservation and cosmetic industries. Despite its recognized bioactive effects, the detailed inhibitory action and interaction of BDMC on tyrosinase and its application in anti-browning processes remain unclear. This study aims to dissect the molecular interactions of BDMC with tyrosinase, elucidate its inhibition mechanism, and assess its efficacy in preventing browning, thereby underpinning its potential as a natural anti-browning agent. Employing a battery of spectroscopic techniques, we characterized the interaction of BDMC with tyrosinase. The anti-browning properties of BDMC were evaluated on fresh-cut apples, and its effect on enzymatic activities related to browning was also investigated. The results indicate that BDMC interacts with tyrosinase in a reversible mixed-type inhibition manner with an IC 50 value of 12.5 ± 0.2 μM. Surface Plasmon Resonance (SPR) results indicated that BDMC presented good binding affinity toward tyrosinase. Fluorescence quenching results showed that BDMC could quench the fluorescence of tyrosinase in a static process. Synchronous fluorescence, circular dichroism spectra, and three-dimensional fluorescence results indicated that interaction of BDMC against tyrosinase resulted in changes of tyrosinase on microenvironment and conformation, thus causing decrease of tyrosinase activity. Copper-chelating results presented that BDMC could chelate to copper with stoichiometric ratio of 1: 2. Molecular docking provided intricate details of how BDMC interacted with tyrosinase. Moreover, BDMC exhibited anti-browning capability on fresh cut apples, and could regulate PPO, POD, and APX activities. The comprehensive analysis proposed in this study consolidated the theoretical basis of BDMC as a tyrosinase inhibitor and supported its potential anti-browning application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this work, four novel angiotensin I-converting enzyme inhibitory (ACEI) peptides were isolated and identified from peony (Paeonia suffruticosa Andr.) seed hydrolysate (PSH) by consecutive chromatography and UPLC-ESI-QTOF-MS/MS. The IC50 values of HWS (0.640 ±0.016 mg/mL) and VLSGF (0.328 ± 0.040 mg/mL) were significantly (p < 0.05) lower than those of the other two peptides. The Lineweaver-Burk plots showed that VLSGF is competitive inhibition against ACE and HWS acted as a mixed-type inhibitor. Meanwhile, the results of molecular docking showed hydrogen interactions between VLSGF/HWS and ACE. In human endothelial cells, the pretreatments of VLSGF and HWS could increase the production of nitric oxide (NO) and the expression of endothelial nitric oxide synthase (eNOS). In addition, they also decreased the reactive oxygen species (ROS) production. These results indicated that it may be possible to use peony seed protein hydrolysate to create ingredients for functional foods.

Human pancreatic lipase (hPL) is a vital digestive enzyme responsible for breaking down dietary fats in humans, inhibiting hPL is a feasible strategy for preventing and treating obesity. This study aims to investigate the structure-activity relationships (SARs) of flavonoids as hPL inhibitors, and to find potent hPL inhibitors from natural and synthetic flavonoids. In this work, the anti-hPL effects of forty-nine structurally diverse naturally occurring flavonoids were assessed and the SARs were summarized. The results demonstrated that the pyrogallol group on the A ring was a key moiety for hPL inhibition. Subsequently, a series of baicalein derivatives were synthesized, while 4'-amino baicalein (ABA) and 4'-pyrrolidine baicalein (PBA) were identified as novel potent hPL inhibitors (IC 50  < 1 μM). Further investigations showed that scutellarein, ABA and PBA potently inhibited hPL in a non-competitive manner (K i  < 1 μM). Among all tested flavonoids, PBA showed the most potent anti-hPL effect in vitro, while this agent also exhibited favorable safety profiles, unique tissue distribution (high exposure level to intestinal system but low exposure levels to deep organs) and impressive in vivo effects for lowering blood triglyceride levels in mice. Collectively, this work uncovers the SARs of flavonoids against hPL, while a newly synthetic flavonoid (PBA) emerges as a potent hPL inhibitor with favorable safety profiles and impressive anti-hPL effects in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The antigenicity of β-lactoglobulin (β-LG) can be influenced by pH values and reduced by epigallocatechin-3-gallate (EGCG). However, a detailed mechanism concerning EGCG decreasing the antigenicity of β-LG at different pH levels lacks clarity. Here, we explore the inhibition mechanism of EGCG on the antigenicity of β-LG at pH 6.2, 7.4 and 8.2 using enzyme-linked immunosorbent assay, multi-spectroscopy, mass spectrometry and molecular simulations. The results of Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) elucidate that the noncovalent binding of EGCG with β-LG induces variations in the secondary structure and conformations of β-LG. Moreover, EGCG inhibits the antigenicity of β-LG the most at pH 7.4 (98.30 %), followed by pH 6.2 (73.18 %) and pH 8.2 (36.24 %). The inhibitory difference is attributed to the disparity in the number of epitopes involved in the interacting regions of EGCG and β-LG. Our findings suggest that manipulating pH conditions may enhance the effectiveness of antigenic inhibitors, with the potential for further application in the food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The postprandial hyperglycemia of diabetic patients is associated with a-amylase and a-glucosidase, searching safer enzyme inhibitors and deciphering their inhibition mechanism are important. In this study, gallocatechin gallate (GCG) was found to exert strong inhibition on α-amylase and α-glucosidase in the mixed-type and non-competitive manners, respectively. GCG could bind with α-amylase and α-glucosidase to form the complexes, which induced conformational changes of the two carbohydrate digestive enzymes. Docking analysis verified that GCG interacted with pivotal amino acids within the active site of α-amylase, while it bound to a site close to the active site of α-glucosidase, which might affect active site, causing declines in a-amylase and α-glucosidase activities. Moreover, the combination of GCG with acarbose increased the inhibition of α-amylase and α-glucosidase and reduced the dosage of acarbose. This study may provide theoretical basis for designing novel functional foods of GCG for the prevention and treatment of diabetes.

Utilising bacteria to produce silver nanoparticles was highly favoured due to its ability to minimise costs and mitigate any potential negative environmental impact. Exopolysaccharides (EPS) extracted from the human gut microbe have demonstrated remarkable efficacy in combating various bacterial infections. Exopolysaccharide (EPS), a naturally occurring biomolecule found in the human gut isolate Proteus mirabilis DMTMMR-11, was characterised using analytical techniques such as Fourier transform infrared spectroscopy (FTIR), 1 H-nuclear magnetic resonance, 13 C-nuclear magnetic resonance (NMR), and chemical composition analysis, which confirms the presence of carbohydrates (81.03 ± 0.23), proteins (4.22 ± 1.2), uronic acid (12.1 ± 0.12), and nucleic acid content (2.44 ± 0.15) in exopolysaccharide. The one factor at a time (OFAT) and response surface methodology (RSM) - central composite design (CCD) approaches were used to optimise the production of Bio-Pm-AgNPs, leading to an increase in yield of up to 1.86 g/l. The Bio-Pm-AgNPs were then subjected to Fourier transform infrared spectroscopy (FTIR) which determines the functional groups, X-ray diffractometer confers that Bio-Pm-AgNPs are crystalline in nature, field emission-scanning electron microscopy (FE-SEM) reveals the morphology of Bio-Pm-AgNPs, energy dispersive X-ray spectroscopy (EDX) confirms the presence of elements like Ag, C and O, high-resolution transmission electron microscopy (HR-TEM) determines that the Bio-Pm-AgNPs are sphere-shaped at 75 nm. Dynamic light scattering (DLS) and zeta potential analysis were also carried out to reveal the physiological nature of Bio-Pm-AgNPs. Bio-Pm-AgNPs have a promising effect on the inhibitory mechanism of Vibrio cholerae cells at a MIC concentration of 20 μg/ml which significantly affects cellular respiration and energy metabolism through glycolysis and TCA cycles by deteriorating the enzyme responsible for ATP and NADH utilisation. The action of Bio-Pm-AgNPs reduces the purity and concentration of nucleic acids, which leads to higher DNA damage. In-vivo analysis reveals that the treatment of Bio-Pm-AgNPs decreased the colonisation of V. cholerae and improved the survival rates in C. elegans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obesity has been recognized as a key risk factor for multiple metabolic disorders, including diabetes, cardiovascular diseases and many types of cancer. Herbal medicines have been frequently used for preventing and treating obesity in many countries, but in most cases, the key anti-obesity constituents in herbs and their anti-obesity mechanisms are poorly understood. This study demonstrated a case study for uncovering the anti-obesity constituents in an anti-obesity herbal medicine (Ginkgo biloba extract) and deciphering their synergistic effects via targeting human pancreatic lipase (hPL). Following screening the anti-hPL effects of eighty herbal medicines, Ginkgo biloba extract (GBE50) was found with the most potent anti-hPL activity. Global chemical profiling of herbal constituents coupling with hPL inhibition assay revealed that the bioflavonoids and several flavonoids in GBE50 were key anti-hPL constituents. Among all tested thirty-eight constituents, sciadopitysin, bilobetin, quercetin, isoginkgetin, and ginkgetin showed potent anti-hPL effects (IC 50 values <2.5 μM). Inhibition kinetic analyses suggested that sciadopitysin, bilobetin, quercetin, isoginkgetin, and ginkgetin acted as non-competitive inhibitors of hPL, with the K i values were <2 μM. Docking simulations revealed that four bioflavonoids (sciadopitysin, bilobetin, isoginkgetin, and ginkgetin) could tightly bind on hPL at cavity 2, which it is different from the binding cavity of quercetin on hPL. Further investigations demonstrated that the combinations of quercetin and one bioflavonoid-type hPL inhibitor (sciadopitysin or bilobetin) showed synergistic anti-hPL effects, suggesting that the multi-components in GBE50 may generate more potent anti-hPL effect. Collectively, our findings uncovered the anti-obesity constituents in GBE50, and explored their anti-hPL mechanisms as well as synergistic effects at molecular levels, which will be very helpful for further understanding the anti-obesity mechanisms of Ginkgo biloba., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hydrothermal liquid digestate has been widely accepted as a substrate in anaerobic digestion (AD) for energy recovery. However, the potential negative impacts of hydrothermal liquid digestate on AD remain unclear. In this study, the organic biodegradability of hydrothermal liquid digestate produced from hydrothermal treatment (HTT) at different temperatures was analyzed, and the formation and degradation process of potential inhibitory substances were discussed. Results demonstrated that the AD lag phase of hydrothermal liquid digestate increased from 3 days at raw liquid digestate to 5-21 days. When the HTT temperature reached 220 °C, the methane yield decreased by 48%, and more than 71% of the organics in the hydrothermal liquid digestate were not utilized by AD. Biorefractory substances, such as fulvic and humic acids, accumulate in the hydrothermal liquid digestate. Potential inhibitory substances from Maillard reactions mainly affect the methanogenesis of AD. Most inhibitory substances were degraded within 7-22 days, with the degradation rate following the order of pyrroles > pyrazines > ketones > imidazoles > indoles. The AD community structure and methane conversion were partially re-established after most inhibitory substances were degraded. This study provides valuable information on eliminating the potential negative effects of hydrothermal liquid digestate on AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glycoside hydrolase family 20 (GH20) β-N-acetyl-d-hexosaminidase (Hex) catalyzes the cleavage of glycosidic linkages in glycans, glycolipids and glycoproteins, and is involved in glycoprotein modification, metabolism of glycoconjugate and the degradation of chitin in fungal cell walls and arthropod exoskeletons. GH84 O-β-N-acetyl-d-glucosaminidase (OGA), which is mechanistically similar related to GH20, participates in the O-GlcNAcylation modification, hydrolyzing the O-GlcNAc moiety from protein acceptors. Hex and OGA are of interest due to their potential for the treatment of disorder diseases and plant protection. Hex inhibitors act as molecular chaperones to treat lysosomal storage disease and as growth regulators to arrest insect molting. Inhibition of OGA is a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer's disease. However, since Hex and OGA exhibit similar active sites, there are challenges in designing highly selective inhibitors. The elucidation of the structural basis of the catalytic mechanism and substrate binding mode of Hex and OGA has provided core information for virtual screening and rational design of inhibitors. A large number of high-potency and selective inhibitors have been developed in the last five years. In this review, we focus on the recent advances in the structural modification, inhibitory activity, binding mechanisms and biological evaluation of Hex and OGA inhibitors, which will facilitate the development of new drugs and agrochemicals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although ADP-dependent sugar kinases were first described in archaea, at present, the presence of an ADP-dependent glucokinase (ADP-GK) in mammals is well documented. This enzyme is mainly expressed in hematopoietic lineages and tumor tissues, although its role has remained elusive. Here, we report a detailed kinetic characterization of the human ADP-dependent glucokinase (hADP-GK), addressing the influence of a putative signal peptide for endoplasmic reticulum (ER) destination by characterizing a truncated form. The truncated form revealed no significant impact on the kinetic parameters, showing only a slight increase in the Vmax value, higher metal promiscuity, and the same nucleotide specificity as the full-length enzyme. hADP-GK presents an ordered sequential kinetic mechanism in which MgADP is the first substrate to bind and AMP is the last product released, being the same mechanism described for archaeal ADP-dependent sugar kinases, in agreement with the protein topology. Substrate inhibition by glucose was observed due to sugar binding to nonproductive species. Although Mg 2+ is an essential component for kinase activity, it also behaves as a partial mixed-type inhibitor for hADP-GK, mainly by decreasing the MgADP affinity. Regarding its distribution, phylogenetic analysis shows that ADP-GK's are present in a wide diversity of eukaryotic organisms although it is not ubiquitous. Eukaryotic ADP-GKs sequences cluster into two main groups, showing differences in the highly conserved sugar-binding motif reported for archaeal enzymes [NX(N)XD] where a cysteine residue is found instead of asparagine in a significant number of enzymes. Site directed mutagenesis of the cysteine residue by asparagine produces a 6-fold decrease in V max , suggesting a role for this residue in the catalytic process, probably by facilitating the proper orientation of the substrate to be phosphorylated., Competing Interests: Declaration of competing interest The authors don't declare any conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Developing naturally active components to control α-amylase/α-glucosidase activity is highly desired for preventing and managing type 2 diabetes. Rapeseed oil is rich in active phenolic compounds and seed oil is a major source of liposoluble inhibitors to these enzymes. However, it remains unclear about the interaction of phenolic compounds in rapeseed oil with α-amylase/α-glucosidase. This study found that the important phenolic compounds from rapeseed oil (Sinapic acid, SA; canolol, CAO; canolol dimer, CAO dimer) possessed effective inhibition performance against α-amylase and α-glucosidase. CAO showed the lowest and highest inhibitory effect, respectively. In the kinetics studies, the inhibition mechanism of SA/CAO/CAO dimer against α-glucosidase was non-competitive, exhibiting a different way from α-amylase. Fluorescence quenching spectra implied that the static processes were responsible for the spontaneous binding between the compounds and enzymes. Fourier-transform infrared spectroscopy (FT-IR) displayed these compounds-induced conformation alterations of α-amylase/α-glucosidase. Molecular docking revealed that SA/CAO/CAO dimer decreased the catalytic efficiency of α-amylase/α-glucosidase through hydrogen bonds, hydrophobic force, or π-π interaction. Molecular dynamics matched well with the experimental and docking results regarding the inhibitory behaviors and interactions toward α-amylase/α-glucosidase. These results demonstrated the potential benefits of phenolic compounds from rapeseed oil in antidiabetic-related activities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In recent years, researches on microalgae inhibition with plant-derived active substances have attracted much attention. In this study, the inhibition of six plant-derived alkaloids (neferine, isoliensinine, linensinine, nuciferine, capsaicin, and hordenine) on bloom-forming cyanobacteria Microcystis aeruginosa were investigated. The results showed that neferine and nuciferine had stronger inhibition on the growth of M. aeruginosa compared with the other four alkaloids, and the relative inhibition rate reached 91.27% and 88.70% at the concentration of 4.5 mg/L after 7 d of exposure, respectively. Different from neferine, nuciferine has no inhibition on Chlorella sp. and Tetradesmus obliquus. It also increased the diversity and species homogeneity of phytoplankton in the environmental water samples. Nuciferine decreased the contents of chlorophyll a and β-carotene in M. aeruginosa with the extension of treatment time, which was 59.40% and 31.90% of the control at the concentration of 1.04 mg/L after 48 h, respectively. After 48 h of nuciferine exposure, the values of fluorescence parameters including maximum quantum yield (Fv/Fm), actual quantum yield of PSII (Yield), non-photochemical quenching (qN and NPQ), and electron transport rates (ETR) of M. aeruginosa cells were significantly decreased and photosynthetic capacity was weakened. The superoxide dismutase (SOD), catalase (CAT), ascorbic acid (ASA), and glutathione (GSH) in the cells were significantly reduced, and the hydrogen peroxide (H 2 O 2 ) and malonaldehyde (MDA) contents continued to accumulate, causing severe oxidative damage. Therefore, the good biological safety and strong specific inhibition of nuciferine makes it have great application prospects in the inhibition of cyanobacteria blooms., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this study, anaerobic batch experiments were conducted to investigate the effect of carbon-based (biochar) and metal-based (nanoscale zero-valent iron, NZVI and zero valent iron, ZVI) mediators on the AD process treating phenolic wastewater. Fresh apricot shell- and wood-derived biochar (BiocharA, BiocharB) could remove the phenol efficiently (77.1% and 86.2%), suggesting that biodegradation cooperated with adsorption had advantage in phenol removal. BiocharB, NZVI and ZVI enhanced the methane production by 17.6%, 23.7% and 23.2%, respectively. Apart from serving as carrier for microbial growth, BiocharB might promote the direct interspecies electron transfer (DIET) since the Anaerolineaceae/Clostridium sensu stricto, which have potential for DIET, were enriched. NZVI and ZVI added systems mainly enhanced the abundance of Clostridium sensu stricto (24.5%, 37.6%) and Methanosaeta. Interestingly, BiocharA inhibited the methanogenesis completely. An inhibitory mechanism was proposed: the exposure of absorbed microbes on the BiocharA to the highly concentrated phenol in biochar' pores resulted in the inhibition of methanogens, especially for Methanosarcina. In conclusion, this study showed that suitable biochar (BiocharB) could serve as an alternative redox mediator for realizing simultaneously the efficient phenol removal and methane production., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, the inhibitory activities of eight caffeoylquinic acids (CQAs) against xanthine oxidase (XOD) in vitro were investigated, and the interaction mechanisms between each compound and XOD were studied. HPLC and fluorescence spectra showed that the inhibitory activities of dicaffeoylquinic acids (diCQAs) were higher than that of monocaffeoylquinic acids (monoCQAs), due to the main roles of hydrophobic interaction and hydrogen bond between XOD and diCQAs. Both the binding constant and the lowest binding energy data indicated that the affinities of diCQAs to XOD were stronger than that of monoCQAs. Circular dichroism showed that the structure of XOD was compacted with the increased of α-helix content, resulting in decreased enzyme catalytic activity. Molecular docking revealed that CQAs preferentially bind to the flavin adenine dinucleotide region in XOD. These results provided the mechanisms of CQAs on inhibiting XOD and the further utilization of CQAs as XOD inhibitors to prevent hyperuricemia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

3-Chymotrypsin-like protease (3CL pro ) is a virally encoded main proteinase that is pivotal for the viral replication across a broad spectrum of coronaviruses. This study aims to discover the naturally occurring SARS-CoV-2 3CL pro inhibitors from herbal constituents, as well as to investigate the inhibitory mechanism of the newly identified efficacious SARS-CoV-2 3CL pro inhibitors. Following screening of the inhibitory potentials of eighty herbal products against SARS-CoV-2 3CL pro , Ginkgo biloba leaves extract (GBLE) was found with the most potent SARS-CoV-2 3CL pro inhibition activity (IC 50  = 6.68 μg/mL). Inhibition assays demonstrated that the ginkgolic acids (GAs) and the bioflavones isolated from GBLE displayed relatively strong SARS-CoV-2 3CL pro inhibition activities (IC 50  < 10 μM). Among all tested constituents, GA C15:0, GA C17:1 and sciadopitysin displayed potent 3CL pro inhibition activities, with IC 50 values of less than 2 μM. Further inhibition kinetic studies and docking simulations clearly demonstrated that two GAs and sciadopitysin strongly inhibit SARS-CoV-2 3CL pro via a reversible and mixed inhibition manner. Collectively, this study found that both GBLE and the major constituents in this herbal product exhibit strong SARS-CoV-2 3CL pro inhibition activities, which offer several promising leading compounds for developing novel anti-COVID-19 medications via targeting on 3CL pro ., (Copyright © 2021. Published by Elsevier B.V.)

Resveratrol and oxyresveratrol are two natural polyhydroxy trans-stilbene products. Previous studies have shown that both of them can effectively inhibit the activity of tyrosinase. However, little attention has been paid to study the difference of their inhibitory mechanism. To reveal this difference, in this work a comparative study on the inhibitory effects of resveratrol and oxyresveratrol against cellular tyrosinase activity and melanin content were investigated by B16F0 cells, and the inhibitory mechanism of them on tyrosinase was revealed by cell-free tyrosinase inhibition, intrinsic fluorescence spectrum, circular dichroism and molecular docking. The results showed that the inhibitory capacity of oxyresveratrol toward tyrosinase activity and melanin formation was better than that of resveratrol. The difference of their inhibitory mechanism may be closely related to the different types of inhibition, the different strength of their interaction with tyrosinase and the different number of hydrogen bonds between them. The data in this study provide a scientific basis for revealing the inhibitory mechanisms of resveratrol and oxyresveratrol toward tyrosinase, and lay an experimental foundation for further development and utilization of them., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Previously, an antioxidant xanthan-oligosaccharide (LW-XG) was successfully produced via bio-degradation of commercial xanthan. In present work, the antibacterial activity and mechanism action of LW-XG against Staphylococcus aureus were studied. Inhibition zone of LW-XG in agar diffusion test was evident and its minimal inhibitory concentration (MIC) against S. aureus was 0.63 mg/mL. Inhibitory mechanism investigation showed that LW-XG increased the cell membrane permeability of S. aureus. Meanwhile, we found that LW-XG could retard the formation of S. aureus biofilm and lower the transcriptional levels of genes (fnbA, fnbB and clfB) related to biofilm formation. Furthermore, LW-XG decreased the Ca 2+ -Mg 2+ -ATPase activity on S. aureus cell membrane and promoted the accumulation of calcium ions in cytoplasm. Overall, LW-XG could inhibit the growth of S. aureus and be regarded as a promising antibacterial substitute in food and pharmaceutical industries., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Excessive coagulation can easily lead to arterial and venous thrombosis, which is the main reason for the evolution of myocardial infarction and cerebrovascular accidents. As a key coagulation factor for the coagulation pathway, thrombin has become a remarkable target for the control of thrombosis. The synthesized peptide P13 with amino acid sequence of N-RGDAGFAGDDAPR was expected to be an inhibitor with higher antithrombotic activity. The results showed that the IC 50 (50% inhibition of thrombin activity) of the peptide P13 was determined by colorimetric method to be 115 µM. And enzyme kinetic experiments showed that P13 was a competitive inhibitor of thrombin with K i  = 106 µM. Fluorescence spectra and three-dimensional fluorescence showed that P13 could alter the secondary structure of thrombin and the microenvironment of certain chromogenic amino acids. P13 can spontaneously bind with thrombin exosite 1 in the form of 1:1 mainly through hydrogen bonding and van der Waals force. And the optimal docking mode of P13 and thrombin was revealed by molecular docking with "-CDOCKER&#95;Energy" of 178.679 kcal mol -1 . This study revealed P13 may become a potential anticoagulant drug widely used after further studies in preclinical and clinical trials., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of the interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Tyrosinase is the rate-limiting enzyme for controlling the production of melanin in the human body, and overproduction of melanin can lead to a variety of skin disorders. In this paper, the inhibitory kinetics of phloretin on tyrosinase and their binding mechanism were determined using spectroscopy, molecular docking, antioxidant assays and chromatography. The spectroscopic results indicate that phloretin reversibly inhibits tyrosinase in a mix-type manner through a multiphase kinetic process with the IC 50 of 169.36 μmol/L. It is shown that phloretin has a strong ability to quench the intrinsic fluorescence of tyrosinase mainly through a static quenching procedure, suggesting that a stable phloretin-tyrosinase complex is generated. Molecular docking results suggest that the dominant conformation of phloretin binds to the gate of the active site of tyrosinase. Moreover, the antioxidant assays demonstrate that phloretin has powerful antioxidant capacity and has the ability to reduce o-dopaquinone to l-dopa just like ascorbic acid. Interestingly, the results of spectroscopy and chromatography indicate that phloretin is a substrate of tyrosinase but also an inhibitor. The possible inhibitory mechanism is proposed, which will be helpful to design and search for tyrosinase inhibitors., (Copyright © 2019. Published by Elsevier B.V.)

Flavonoids are natural polyphenolic compounds from plants. As a new biotechnological algaecide, the molecular mechanism of plant flavonoids on the inhibition of Microcystis aeruginosa is still unknown. Therefore, in this study, we analyzed the variation of expressions of photosynthesis-related genes, microcystin synthesis-related genes and the genes involved in N and P acquisition in M. aeruginosa under the flavonoids stress. The results showed that the expression of psbD1, psaB and rbcL related to photosynthesis were influenced by three flavonoids but with different changing tendencies. The transcription of mcyA, mcyD and mcyH related to microcystin synthesis were decreased after 5-d of exposure, which could block microcystin synthesis. Meanwhile, flavonoids treatments resulted in the inhibition of N and P acquisition related genes transcription to affect the absorption of N and P in algal cells, and further influenced the physiological metabolic process of M. aeruginosa., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this paper, the inhibitory kinetics of aloe-emodin on the activity of tyrosinase and the inhibitory mechanism have been investigated by using spectroscopic and molecular docking techniques. The results showed that aloe-emodin inhibited tyrosinase activity in a competitive manner. The binding constants, number of binding sites and thermodynamic parameters obtained at different temperature suggested that aloe-emodin spontaneously binds to tyrosinase at one binding site, mainly via electrostatic forces. Analysis by UV-vis absorption (UV), circular dichroism (CD) and molecular docking indicated that aloe-emodin bound directly into the catalytic cavity and that binding of aloe-emodin to tyrosinase induced conformational changes of the enzyme and blocked the catalytic center of the enzyme preventing binding of the substrate, which caused the inhibition of the tyrosinase activity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hepatitis C virus, Nonstructural 3 helicase (NS3h) protein is a well-studied segment of Non-structural 3/4 A helicase-protease protein that is crucial for the RNA duplex unwinding and RNA translocation during the process of HCV replication. Similar to other HCV nonstructural proteins, helicase is a potential target for antiviral drugs and several antiviral molecules have been used to target the RNA-binding cleft, despite the fact that none of those helicase antivirals have advanced the clinical trials. Compound 2t9 (5-bromo-1H-indol-3-yl acetic acid) has been identified through the integrated strategies and considered as a potential lead compound for the inactivation of HCV helicase. This inhibitor bind to the 3´-terminal RNA-binding cleft, and reduced the RNA binding and unwinding activity of the targeted protein. In the current study, using all-atom molecular dynamic simulation and correlations network strategy, we scrutinized the inhibitory mechanism of compound 2t9 that needs to be elucidated for the improvement of indole-based and similar HCV helicase inhibitors. Consequently, by comparing the structural dynamics of free (NS3h WT ) and bound (NS3h/2t9 WT ) protein, we identified that the inhibitor-bound protein achieved a conformation resemblance to the open conformation, where the RNA is displaced results in destabilization of RNA-binding cleft, disruption in ATP/ADP binding site and alter the inter-domain communication. The results were evaluated by using the W501 L mutated system. The information based on detailed dynamic aspects of the drug targeted protein will facilitate the researchers in the development of HCV antiviral drugs., (Copyright © 2018. Published by Elsevier Ltd.)

Controlling the activity of tyrosinase, which plays an important role in melanin synthesis, is essential endeavor in the field of medicine, food, cosmetics, and agriculture. Baicalein is a widely available inhibitor of tyrosinase. The mechanism of this inhibition was studied through an integrated approach coupling enzyme kinetics, multiple types of spectroscopy and computational simulation. Baicalein conspicuously inhibited the diphenolase activity with an IC 50 value of 0.11 mM. The inhibtion kinetics indicated that baicalein was a mix-type tight binding inhibitor with a K i of 0.17 mM and an α value of 0.56. UV absorption spectra showed that a complex formed. Baicalein quenched the fluorescence via both static and dynamic quenching though a single binding site with a binding constant of 278,000 M -1 . Thermodynamic parameters suggested spontaneous binding through hydrogen bonding and van der Waals forces. The binding distance was estimated at 3.41 nm. Phase diagram analysis suggested baicalein induced at least two structurally distinct intermediates. Synchronous fluorescence and three-dimensional fluorescence spectra showed blue shift of the maximum emission wavelength. The content of α-helix decreased from 32.67% to 29.00% according to circular dichroism spectra. It was revealed that baicalein induced conformational changes in tyrosinase and enhanced the hydrophobicity of the microenvironment around Trp residues. Docking simulations predicted that baicalein mainly bound tyrosinase via its Met280 residue. This research will provide reliable basis concerning the inhibitory mechanism of baicalein against tyrosianse, and therefore eventually contribute to development of anti-tyrosinase agents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Although some naturally occurring polyphenols have been found to inhibit amyloid β (Aβ) fibril formation and reduce neuron cell toxicity in vitro, their exact inhibitory mechanism is unknown. In this work, discontinuous molecular dynamics combined with the PRIME20 force field and a newly built inhibitor model are performed to examine the effect of vanillin, resveratrol, curcumin, and epigallocatechin-3-gallate (EGCG) on the aggregation of Aβ(17-36) peptides. Four sets of peptide/inhibitor simulations are performed in which inhibitors (1) bind to Aβ(17-36) monomer (2) interfere with Aβ(17-36) oligomerization (3) disrupt a pre-formed Aβ(17-36) protofilament, and (4) prevent the growth of Aβ(17-36) protofilament. The single-ring compound, vanillin, slightly slows down but cannot inhibit the formation of a U-shaped Aβ(17-36) protofilament. The multiple-ring compounds, EGCG, resveratrol, and curcumin, redirect Aβ(17-36) from a fibrillar aggregate to an unstructured oligomer. The three aromatic groups of the EGCG molecule are in a stereo (nonplanar) configuration, helping it contact the N-terminal, middle, and C-terminal regions of the peptide. Resveratrol and curcumin bind only to the hydrophobic residues near peptide termini. The rank order of inhibitory effectiveness of Aβ(17-36) aggregation is as follows: EGCG > resveratrol > curcumin > vanillin, consistent with experimental findings on inhibiting full-length Aβ fibrillation. Furthermore, we learn that the inhibition effect of EGCG is specific to the peptide sequence, while those of resveratrol and curcumin are non-specific in that they stem from strong interference with hydrophobic side-chain association, regardless of the residues' location and peptide sequence. Our studies provide molecular-level insights into how polyphenols inhibit Aβ fibril formation, knowledge that could be useful for designing amyloid inhibitors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)