Isolation of an α-glucosidase Inhibitor from Houttuynia cordata Thunb. and Its In vitro and In vivo Hypoglycemic Bioactivity.

The Houttuynia cordata Thunb. belongs to the Saururaceae family and is a well-known medicine and food homologous plant. Herein, the isolation of an α-glucosidase inhibitor from Houttuynia cordata Thunb. and characterization of its in vitro and in vivo hypoglycemic bioactivities are reported. We optimized the extraction conditions and isolated neochlorogenic acid (nCGA), which has α-glucosidase inhibitory activity from Houttuynia cordata Thunb. for the first time. nCGA competed with glucose for the α-glucosidase binding site, with a 50% inhibitory concentration (IC50) of 0.711 mg/mL. In vivo experiments in zebrafish showed that effects of nCGA on blood glucose varied by its concentrations. In particular, 4 mg/L nCGA significantly decreased the blood glucose level and inhibited effects of α-glucosidase in zebrafish. This work provides a theoretical basis for the extraction of hypoglycemic active ingredients from Houttuynia cordata Thunb. and a foundation for the development of natural and effective α-glucosidase inhibitors.

Influence of Degree of Polymerization of Low-Molecular-Weight Chitosan Oligosaccharides on the α-Glucosidase Inhibition.

Chitosan oligosaccharide (COS) is a bioactive compound derived from marine by-products. COS consumption has been demonstrated to lower the risk of diabetes. However, there are limited data on the inhibitory effect of low-molecular-weight COSs with different degrees of polymerization (DP) on α-glucosidase. This study investigates the α-glucosidase inhibitory activity of two low-molecular-weight COSs, i.e., S-TU-COS with DP2−4 and L-TU-COS with DP2−5, both of which have different molecular weight distributions. The inhibition constants of the inhibitors binding to free enzymes (Ki) and an enzyme−substrate complex (Kii) were investigated to elucidate the inhibitory mechanism of COSs with different chain lengths. The kinetic inhibition model of S-TU-COS showed non-completive inhibition results which are close to the uncompetitive inhibition results with Ki and Kii values of 3.34 mM and 2.94 mM, respectively. In contrast, L-TU-COS showed uncompetitive inhibition with a Kii value of 5.84 mM. With this behavior, the IC50 values of S-TU-COS and L-TU-COS decreased from 12.54 to 11.84 mM and 20.42 to 17.75 mM, respectively, with an increasing substrate concentration from 0.075 to 0.3 mM. This suggests that S-TU-COS is a more potent inhibitor, and the different DP of COS may cause significantly different inhibition (p < 0.05) on the α-glucosidase activity. This research may provide new insights into the production of a COS with a suitable profile for antidiabetic activity.

The development of novel cytochrome P450 2J2 (CYP2J2) inhibitor and the underlying interaction between inhibitor and CYP2J2.

Human Cytochrome P450 2J2 (CYP2J2) as an important metabolic enzyme, plays a crucial role in metabolism of polyunsaturated fatty acids (PUFAs). Elevated levels of CYP2J2 have been associated with various types of cancer, and therefore it serves as a potential drug target. Herein, using a high-throughput screening approach based on enzymic activity of CYP2J2, we rapidly and effectively identified a novel natural inhibitor (Piperine, 9a) with IC50 value of 0.44 µM from 108 common herbal medicines. Next, a series of its derivatives were designed and synthesised based on the underlying interactions of Piperine with CYP2J2. As expected, the much stronger inhibitors 9k and 9l were developed and their inhibition activities increased about 10 folds than Piperine with the IC50 values of 40 and 50 nM, respectively. Additionally, the inhibition kinetics illustrated the competitive inhibition types of 9k and 9l towards CYP2J2, and Ki were calculated to be 0.11 and 0.074 µM, respectively. Furthermore, the detailed interaction mechanism towards CYP2J2 was explicated by docking and molecular dynamics, and our results revealed the residue Thr114 and Thr 315 of CYP2J2 were the critical sites of action, moreover the spatial distance between the carbon atom of ligand methylene and Fe atom of iron porphyrin coenzyme was the vital interaction factor towards human CYP2J2.

Biodegradation of wastewater in alternating aerobic-anoxic lab scale pilot plant by Alcaligenes sp. S3 isolated from agricultural field.

The isolated microbial Alcaligenes sp. S3 from the agricultural field was used for the biodegradation of synthetic wastewater containing atrazine. This study was conducted in an alternating aerobic-anoxic lab scale pilot plant. The performance of continuously operated pilot plant was evaluated in three different phases with varying atrazine concentration. The best performance of plant was observed in phase-II. The atrazine (200 mg/L) having COD value 1356 mg/L was used with varying flow rate and 90.56% COD removal was obtained at a flow rate of 300 mL/h on 122th day of operation. The effect of process parameter like pH and DO on the performance of the reactor was studied. The GC-MS analysis was investigated, and urea was found the intermediate/metabolites of atrazine biodegradation. The kinetic parameters such as half saturation rate constant (Ks) 106.80 mg/L; maximum specific growth rate (µmax) 0.208 per day and inhibition constant (Ki) 374.91 mg/L were evaluated by Andrew-Haldane model.

New Perspectives on the Risks of Hydroxylated Polychlorinated Biphenyl (OH-PCB) Exposure: Intestinal Flora α-Glucosidase Inhibition.

Polychlorinated biphenyls (PCBs) are a group of colorless and odorless environmental pollutants with a wide range of toxic effects. Some PCBs, especially less chlorinated ones, will rapidly undergo phase I metabolism after entering the body, and hydroxylated polychlorinated biphenyls (OH-PCBs) are the main metabolites of PCBs. Intestinal flora α-glucosidase is a common carbohydrate-active enzyme which is ubiquitous in human intestinal flora. It can convert complex dietary polysaccharides into monosaccharides, assisting the body in degrading complex carbohydrates and providing energy for the survival and growth of bacterial flora. The present study aims to investigate the inhibition of the activity of intestinal flora α-glucosidase by OH-PCBs. 4-Nitrophenyl-α-D-glucopyranoside (PNPG) was used as a probe substrate for α-glucosidase, and in vitro incubation experiments were conducted to study the inhibition of 26 representative OH-PCBs on α-glucosidase. Preliminary screening of in vitro incubation was performed with 100 µM of OH-PCBs. The results showed that 26 OH-PCBs generally exhibited strong inhibition of α-glucosidase. The concentration-dependent inhibition and half inhibition concentrations (IC50s) of OH-PCBs on α-glucosidase were determined. 4'-OH-PCB 86 and 4'-OH-PCB 106 were chosen as representative OH-PCBs, and the inhibition kinetic parameters (Kis) of inhibitors for α-glucosidase were determined. The inhibition kinetic parameters (Kis) of 4'-OH-PCB 86 and 4'-OH-PCB 106 for α-glucosidase are 1.007 µM and 0.538 µM, respectively. The silico docking method was used to further analyze the interaction mechanism between OH-PCBs and α-glucosidase. All these results will help us to understand the risks of OH-PCB exposure from a new perspective.

Optimization of a Novel Tyrosinase Inhibitory Peptide from Atrina pectinata Mantle and Its Molecular Inhibitory Mechanism.

In order to realize the multi-level utilization of marine shellfish resources and to develop the potential biological activity of processing by-products of Atrina pectinata, gelatin was extracted from the mantle and the potential whitening effect of its enzymatic peptides was explored. Taking tyrosinase inhibitory activity as the evaluation index, the enzyme hydrolysate process was optimized by response-surface methodology, and the optimal enzyme hydrolysate conditions were as follows: pH 5.82, 238 min enzyme hydrolysate time, and temperature of 54.5 °C. Under these conditions, the tyrosinase inhibition activity of Atrina pectinata mantle gelatin peptide (APGP) was 88.6% (IC50 of 3.268 ± 0.048 mg/mL). The peptides obtained from the identification were separated by ultrafiltration and LC-MS/MS, and then four new peptides were screened by molecular docking, among which the peptide Tyr-Tyr-Pro (YYP) had the strongest inhibitory effect on tyrosinase with an IC50 value of 1.764 ± 0.025 mM. The molecular-docking results indicated that hydrogen bonding is the main driving force for the interaction of the peptide YYP with tyrosinase. From the Lineweaver-Burk analysis, it could be concluded that YYP is inhibitory to tyrosinase and exhibits a mixed mechanism of inhibition. These results suggest that YYP could be widely used as a tyrosinase inhibitor in whitening foods and pharmaceuticals.

Optimization and Molecular Mechanism of Novel α-Glucosidase Inhibitory Peptides Derived from Camellia Seed Cake through Enzymatic Hydrolysis.

In recent years, food-derived hypoglycemic peptides have received a lot of attention in the study of active peptides, but their anti-diabetic mechanism of action is not yet clear. In this study, camellia seed cake protein (CSCP) was used to prepare active peptides with α-glucosidase inhibition. The optimization of the preparation of camellia seed cake protein hydrolyzed peptides (CSCPH) was conducted via response surface methodology (RSM) using a protamex with α-glucosidase inhibition as an indicator. The optimal hydrolysis conditions were pH 7.11, 4300 U/g enzyme concentration, 50 °C hydrolysis temperature, and 3.95 h hydrolysis time. Under these conditions, the α-glucosidase inhibition rate of CSCPH was 58.70% (IC50 8.442 ± 0.33 mg/mL). The peptides with high α-glucosidase inhibitory activity were isolated from CSCPH by ultrafiltration and Sephadex G25. Leu-Leu-Val-Leu-Tyr-Tyr-Glu-Tyr (LLVLYYEY) and Leu-Leu-Leu-Leu-Pro-Ser-Tyr-Ser-Glu-Phe (LLLLPSYSEF) were identified and synthesized for the first time by Liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) analysis and virtual screening with IC50 values of 0.33 and 1.11 mM, respectively. Lineweaver-Burk analysis and molecular docking demonstrated that LLVLYYEY was a non-competitive inhibitor of α-glucosidase, whereas LLLLPSYSEF inhibited α-glucosidase, which displayed a mixed inhibition mechanism. The study suggests the possibility of using peptides from Camellia seed cake as hypoglycaemic compounds for the prevention and treatment of diabetes.

An overview on the synthetic urease inhibitors with structure-activity relationship and molecular docking.

Urease is a kind of enzyme which could be found in various bacteria, fungi, plants, and algae, which can quickly catalyze the hydrolysis of urea into ammonia and carbon dioxide. With the ammonia concentration increasing, the activity of Helicobacter pylori has got an obvious enhancement and leads to mucosal damage in the stomach, gastroduodenal infection, peptic ulcers, and gastric cancer. The infectious diseases caused by Helicobacter pylori can be controlled to a certain extent by inhibiting urease activity with urease inhibitors. Hence, studies of urease inhibitors have attracted great attention all over the world and a variety of effective urease inhibitors have been synthesized in recent years. In this review, we will draw summaries for these inhibitors including urease inhibitory activity, inhibition kinetics, structure-activity relationship, and molecular docking. The collected information is expected to provide rational guidance and effective strategy to develop novel, potent, and safe urease inhibitors for better practical applications in the future.

Novel Peptide Sequences with ACE-Inhibitory and Antioxidant Activities Derived from the Heads and Bones of Hybrid Groupers (Epinephelus lanceolatus × Epinephelus fuscoguttatus).

The heads and bones of hybrid groupers are potential precursors for angiotensin-converting enzyme (ACE)-inhibitory and antioxidant peptides. The aim of this study was to isolate the dual-action peptides from the Alcalase-treated head and bone hydrolysate of hybrid groupers followed by identification of the novel peptides. The stability of these peptides against stimulated in vitro gastrointestinal digestion (SGID) was also determined. Fraction HB-IV (less than 1 kDa) obtained from ultrafiltration showed the strongest ACE-inhibition ability (IC50: 0.28 mg/mL), which was comparable to the potency of the commercial supplement, PeptACE (IC50: 0.22 mg/mL). This fraction also demonstrated the highest hydroxyl radical scavenging and metal-chelating activities. However, further fractionation of HB-IV by a series of chromatography resulted in peptide fractions of reduced ACE-inhibitory and antioxidant activities. The hydroxyl radical scavenging and reduction potential of HB-IV were enhanced, whereas ACE-inhibitory and metal-chelating activities were reduced following SGID. A total of 145 peptide sequences were identified from HB-IV, of which 137 peptides were novel to the BIOPEP database. The results suggested that the bioactive peptides isolated from the heads and bones of hybrid groupers could be used as functional foods/ingredients with potential ACE-inhibitory and antioxidant effects.

Cabozantinib Carries the Risk of Drug-Drug Interactions via Inhibition of UDPglucuronosyltransferase (UGT) 1A9.

BACKGROUND: Cabozantinib is a multiple receptor tyrosine kinases inhibitor (TKI) approved to treat progressive, metastatic medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma. Drugdrug interactions (DDIs) for cabozantinib have been identified involving the role of cytochromes P450. Although the previous study reported that cabozantinib showed a slight inhibition of UDP-glucuronosyltransferase (UGT) 1A1 at the highest concentration tested, there are no reports on the potential for UGTs-mediated-DDIs. Hence, the current study aims to address this knowledge gap. OBJECTIVE: This study aimed to investigate the inhibitory effect of cabozantinib on human UGTs and to quantitatively evaluate the DDI potential via UGT inhibition. METHODS: The inhibitory effects of cabozantinib on UGTs were determined by measuring the formation rates for 4- methylumbelliferone (4-MU) glucuronide and trifluoperazine N-glucuronide using recombinant human UGT isoforms in the absence or presence of cabozantinib. Inhibition kinetic studies were conducted to determine the type of inhibition of cabozantinib on UGTs and the corresponding inhibition constant (Ki) value. In vitro-in vivo extrapolation (IVIVE) was further employed to predict the potential risk of DDI in vivo. RESULTS: Cabozantinib displayed potent inhibition of UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7, and 2B15. Cabozantinib exhibited noncompetitive inhibition towards UGT1A1 and 1A3 and inhibition towards UGT1A7 and 1A9. The Ki,u values (mean ± standard deviation) were calculated to be 2.15±0.11 µM, 0.83±0.05 µM, 0.75±0.04 µM and 0.18 ± 0.10 µM for UGT1A1, 1A3, 1A7 and 1A9, respectively. Co-administration of cabozantinib at the clinically approved dose of 60 mg/day or 140 mg/day may result in approximately a 26% to 60% increase in the systemic exposure of drugs predominantly cleared by UGT1A9, implying a high risk of DDIs. CONCLUSION: Cabozantinib has the potential to cause DDIs via the inhibition of UGT1A9; therefore, additional attention should be paid to the safety of the combined use of cabozantinib and drugs metabolized by UGT1A9.

Pomegranate peel-derived punicalagin: Ultrasonic-assisted extraction, purification, and its α-glucosidase inhibitory mechanism.

The pomegranate peel is a by-product of pomegranate fruit rich in polyphenols. In this study, pomegranate peel polyphenols were explored using LC-MS/MS, and punicalagin was the most abundant compound. The highest yield (505.89 ± 1.73 mg/g DW) of punicalagin was obtained by ultrasonic-assisted extraction (UAE) with the ethanol concentration of 53%, sample-to-liquid ratio of 1:25 w/v, ultrasonic power of 757 W, and extraction time of 25 min. Punicalagin was further purified by the macroporous resin D101 and prep-HPLC, reaching the purity of 92.15%. The purified punicalagin had the IC50 of 82 ± 0.02 µg/mL against α-glucosidase, similar to the punicalagin standard with IC50 of 58 ± 0.014 µg/mL, both exhibiting a mixed inhibitory mechanism. Molecular docking further revealed that a steric hindrance with the intermolecular energy of -7.99 kcal/mol was formed between punicalagin and α-glucosidase. Overall, pomegranate peel is a promising source of punicalagin to develop anti-diabetic functional foods.

A new functionality study of vanillin as the inhibitor for α-glucosidase and its inhibition kinetic mechanism.

Vanillin is a natural phenolic compound mainly used as flavors in food industry. In this work, a new functionality of vanillin as the α-glucosidase inhibitor was studied based on the inhibition kinetic mechanism. The inhibitory effect (IC50) of vanillin against α-glucosidase was 28.34 ± 0.89 mg/mL, which belongs to mixed inhibition mechanism and its process was spontaneous. Vanillin could bind to α-glucosidase by hydrophobic interactions and hydrogen bonds with -8.42 kcal/mol intermolecular energy to form the steric hindrance. The average binding distances was calculated as 2.20 nm according to energy transfer theory. In addition, the protein secondary structure and denaturation temperature (decreasing about 10 °C) were changed significantly after vanillin binding to α-glucosidase, resulting in an inhibitory effect. The findings of this research provide insights for the development of vanillin as potential inhibitor for α-glucosidase in special dietary foods.

Inhibition Kinetics and Mechanism of Glutathione and Quercetin on Acrylamide in the Low-Moisture Maillard Systems.

ABSTRACT: The inhibition kinetics of glutathione (GSH) and quercetin on acrylamide (AA) formation in the low-moisture Maillard systems were investigated at 180°C. The inhibition rates in an equal-molar asparagine-glucose (Asn-Glc) system were higher than those in an asparagine-fructose (Asn-Fru) system, and the maximum inhibition rates for AA were 57.75% with 10-2 mol L-1 GSH and 51.38% with 10-1 mol L-1 quercetin. The Logistic-Index dynamic model and two consecutive simplified first-order kinetic models were well fitted to the changes of AA in the Asn-Glc system. The kinetics results suggested that the predominant inhibition effect of GSH on AA could be attributed to the competitive reaction between GSH and Asn for the consumption of Glc. The kinetic results and high-pressure liquid chromatography-tandem mass spectrometry analysis of the inhibitory effect of quercetin on AA indicated that quercetin might mitigate AA through the binding reaction of quercetin decomposition products and Maillard intermediate products. These experimental results provide theoretical data that may be useful to control the formation of AA during food thermal processing.

Screening and identifying of α-amylase inhibitors from medicine food homology plants: Insights from computational analysis and experimental studies.

There is a growing interest in screening α-amylase inhibitors from natural products for application in the development of new antidiabetic drugs or functional foods. In this study, a structure-based virtual screening was applied to rapidly identify the α-amylase inhibitors from medicine food homology (MFH) plants. Similarity search, docking & scoring were used for further filter small molecules. As a result, 21 corresponding potential α-amylase inhibitors from MFH plants were obtained. And, six polyphenol compounds (curcumin, procyanidins, epicatechin gallate (ECG), epigallocatechin gallate (EGCG), hesperidin, and puerarin) were highlighted for further verification after a thorough assessment of the classification of hit molecules as well as docking scores. The results of the enzyme inhibition test showed that ECG, EGCG, and procyanidins had the better binding ability of α-amylase among these six polyphenols. The Ki values of ECG, EGCG, and procyanidins on α-amylase were 0.70, 1.68, and 0.24, respectively. The CD spectra results indicated that the three polyphenols can cause conformational changes in α-amylase. PRACTICAL APPLICATIONS: A structure-based virtual screening method for rapid identifying α-amylase inhibitors from MFH plants was developed successfully in this study. These findings suggested that natural polyphenols such as ECG, EGCG, and procyanidins may be a potential inhibitor of α-amylase which could be used as a nutrient supplement for the prevention of diabetes mellitus or can be further used in the development of hypoglycemic drugs. At the same time, it can provide theoretical guidance for the better utilization and development of medicine food homology plants containing these potential α-amylase inhibitors. Moreover, this work may provide ideas and references for the screening of other target protein inhibitors.

Preparation and Irreversible Inhibition Mechanism Insight into a Recombinant Kunitz Trypsin Inhibitor from Glycine max L. Seeds.

Soybean Kunitz trypsin inhibitor (SKTI), extracted from soybean (Glycine max L.) seeds, possesses insect resistance and anti-tumor properties. But its specific mechanisms of action are not yet known. This article reports an efficient method to produce recombinant SKTI (rSKTI) in Escherichia coli, reveals some biochemical properties of rSKTI, and discusses the inhibition mechanism of SKTI. The rSKTI was expressed as inclusion body in E. coli BL21 (DE3). After refolding, the active rSKTI was obtained and was further purified with anion-exchange chromatography (DEAE-FF) efficiently. There were similar biochemical properties between SKTI and rSKTI. The optimum pH and the optimum temperature were pH 8.0 and 35 °C, respectively, being stable during pH 7.0-11.0 and below 37 °C. The activity against trypsin was inhibited by Co2+, Mn2+, Fe3+, Al3+, and epoxy chloropropane. Inhibition kinetic assay of SKTI against trypsin as Lineweaver-Burk plots analysis both showed an unchanged Km and a decreased Vmax with N-benzoyl-L-arginine ethyl ester (BAEE) as substrate. Molecular modeling showed Arg63 of SKTI (active residue of SKTI) that interacts with four residues of trypsin, including three catalytic site (His57, Asp102, and Ser195) and one binding site (Asp189), forming five interactions. These provide reference for understanding the inhibition mechanism of such kind of Kunitz trypsin inhibitors.

Distribution and Characteristics of Polyphenoloxidase from Pacific White Shrimp (Litopenaeus vannamei).

Distribution of polyphenoloxidase (PPO) from different anatomical parts of Pacific white shrimp was examined. Among all parts, cephalothorax possessed the maximal PPO activity (P < 0.05), followed by pereopods, telson, pleopods, carapace, cuticle, and muscle, respectively. The higher PPO activity in cephalothorax was in line with the greater melanosis in this part during chilled storage. According to activity-staining toward 3,4-dihydroxy-ʟ-phenylalanine (ʟ-DOPA), PPO exhibited an activity band with a molecular weight (MW) of 210 kDa. When cephalothorax PPO was purified using ammonium sulfate precipitation and a series of chromatographic techniques, involving DEAE-Sepharose anion exchange and Sephadex G-75 gel filtration columns, homogeneity was obtained. Based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and native-PAGE, the Sephadex G-75 fraction showed a single band. The MW band on SDS-PAGE and gel filtration was estimated as 210 kDa, suggesting a monomeric molecule. For the inhibitor study, cysteine and 4-hexylresorcinol showed competitive inhibition toward PPO, while epigallocatechin gallate and kojic acid demonstrated mixed-type inhibition toward PPO. PRACTICAL APPLICATION: Melanosis (black spot formation) triggered by polyphenoloxidase (PPO) drastically reduces the shelf-life of shrimp. PPO was localized in several anatomical parts of Pacific white shrimp with varying activities. Certain compounds, including cysteine, 4-hexylresorcinol, epigallocatechin gallate, and kojic acid, showed PPO inhibitory activity with different modes of inhibition. The obtained information provided a promising method for manufacturers to keep the prime eating quality of Pacific white shrimp throughout postmortem transportation and storage using selected PPO inhibitors.

Per- and polyfluoroalkyl substances display structure-dependent inhibition towards UDP-glucuronosyltransferases.

Per- and polyfluoroalkyl substances (PFASs) are a large group of chemicals and can be detected in environmental and human samples all over the world. Toxicity of existing and emerging PFASs will be a long-term source of concern. This study aimed to investigate structure-dependent inhibitory effects of 14 PFASs towards the activity of 11 UDP-glucuronosyltransferase (UGT) isoforms. In vitro UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed to determine the inhibition of PFASs towards different UGT isoforms. All the PFASs showed <75% of inhibition or stimulation effects on UGT1A3, UGT1A7, UGT1A9, UGT2B4, UGT2B7 and UGT2B17. However, PFASs showed broad inhibition on the activity of UGT1A1 and UGT1A8. The activity of UGT1A1 was inhibited by 98.8%, 98%, 79.9%, 77.1%, and 76.9% at 100 µmoL/L of perfluorodecanoic acid (PFDA), perfluorooctanesulfonic acid potassium salt (PFOS), perfluorotetradecanoic acid (PFTA), perfluorooctanoic acid (PFOA) and perfluorododecanoic acid (PFDoA), respectively. UGT1A8 was inhibited by 97.6%, 94.8%, 86.3%, 83.4% and 77.1% by PFDA, PFTA, perfluorooctadecanoic acid (PFOcDA), PFDoA and PFOS, respectively. Additionally, PFDA significantly inhibited UGT1A6 and UGT1A10 by 96.8% and 91.6%, respectively. PFDoA inhibited the activity of UGT2B15 by 88.2%. PFDA and PFOS exhibited competitive inhibition towards UGT1A1, and PFDA and PFTA showed competitive inhibition towards UGT1A8. The inhibition kinetic parameter (Ki) were 3.15, 1.73, 13.15 and 20.21 µmoL/L for PFDA-1A1, PFOS-1A1, PFDA-1A8 and PFTA-1A8, respectively. The values were calculated to be 0.3 µmoL/L and 1.3 µmoL/L for the in vivo inhibition of PFDA towards UGT1A1-and UGT1A8-catalyzed metabolism of substances, and 0.2 µmoL/L and 2.0 µmoL/L for the inhibition of PFOS towards UGT1A1 and the inhibition of PFTA towards UGT1A8, respectively. Molecular docking indicated that hydrogen bonds and hydrophobic interactions contributed to the interaction between PFASs and UGT isoforms. In conclusion, exposure to PFASs might inhibit the activity of UGTs to disturb metabolism of endogenous compounds and xenobiotics. The structure-related effects of PFASs on UGTs would be very important for risk assessment of PFASs.

Fast Biodegradation of Diesel Hydrocarbons at High Concentration by the Sophorolipid-Producing Yeast Candida catenulata KP324968.

In the last decades, biodegradation as an environmentally friendly approach has raised interest in connection with the removal of hydrocarbon pollutants. Its capacity for removing pollutants strongly depends on the type of living cell and environmental conditions. The degradative activity of a new sophorolipid-producing yeast, Candida catenulata KP324968, in the removal of high concentrations of diesel from effluents was statistically evaluated considering the initial pH, the agitation speed, and the initial diesel concentration. The optimal setting of the operational variables at an initial pH of 4.7, an agitation speed of 204 rpm, and an initial diesel concentration of 93.4 g L-1 resulted in the highest total petroleum hydrocarbon removal efficiency: about 82.1% after 6 days (biodegradation rate: 0.378 g gcell-1 h-1). During the cell growth phase, the emulsification index in the medium increased and reached its highest level at 64.6% after 48 h. Further tests indicated that the emulsification capacity was obtained by in situ production of two sophorolipid molecules with an m/z of 533 and 583. In summary, its effective diesel removal and high emulsification capacity makes C. catenulata KP324968 an attractive candidate yeast for the degradation of hydrocarbons from aqueous environments.

The natural anthraquinones from Rheum palmatum induced the metabolic disorder of melatonin by inhibiting human CYP and SULT enzymes.

Melatonin (Mel) as an endogenous hormone, has been widely used in clinic for multiple therapeutic purposes. Further, the natural anthraquinones were widespread in various plants including herbs, foods, and some flavoring agents. The present work aims to evaluate the metabolic disorder of Mel caused by various common herbs and further identify their underlying mechanism. More importantly, the relationships between inhibitory activity and their structures were also investigated. Our results demonstrate that some herbs containing anthraquinone derivatives exhibited strong inhibition on Mel metabolism. Additionally, five anthraquinones from R. palmatum could inhibit phase I and II metabolism of Mel with a mixed inhibition kinetic model based on the mechanism of inhibiting human CYP1A1, 1A2, and SULT1A1. At last, the influence of R. palmatum and its five major components on the Mel metabolism were verified in human primary hepatocytes. In conclusion, our studies elucidated that herbs or foods containing abundant anthraquinones such as R. palmatum will cause a metabolic disorder of Mel, and should be avoided to combined application with Mel in clinic.