Decolorization and detoxication of malachite green by engineered Saccharomyces cerevisiae expressing novel thermostable laccase from Trametes trogii.

Malachite Green (MG) is a widely used industrial dye that is hazardous to health. Herein, the decolourisation and detoxification of MG were achieved using the engineered Saccharomyces cerevisiae expressing novel thermostable laccase lcc1 from Trametes trogii. The engineered strain RCL produced a high laccase activity of 121.83 U L-1. Lcc1 was stable at temperatures ranging from 20 ℃ to 60 ℃ and showed a high tolerance to organic solvents. Moreover, Lcc1 could decolorize different kinds of dyes (azo, anthraquinone and triphenylmethane), among which, the decolorization ability of MG is the highest, reaching 95.10 %, and the decolorization rate of other triphenylmethane dyes also over 50 %. The RCL decolorized about 95 % of 50 mg L-1 of MG dye in 10 h at 30 ℃. The MG degradation products were analyzed. The industrial application potential of the RCL was evaluated by treating industrial wastewater and the decolourisation rates were over 90 %.

Cellulose de-polymerization is selective for bioethanol refinery and multi-functional biochar assembly using brittle stalk of corn mutant.

As lignocellulose recalcitrance principally restricts for a cost-effective conversion into biofuels and bioproducts, this study re-selected the brittle stalk of corn mutant by MuDR-transposon insertion, and detected much reduced cellulose polymerization and crystallinity. Using recyclable CaO chemical for biomass pretreatment, we determined a consistently enhanced enzymatic saccharification of pretreated corn brittle stalk for higher-yield bioethanol conversion. Furthermore, the enzyme-undigestible lignocellulose was treated with two-step thermal-chemical processes via FeCl2 catalysis and KOH activation to generate the biochar with significantly raised adsorption capacities with two industry dyes (methylene blue and Congo red). However, the desirable biochar was attained from one-step KOH treatment with the entire brittle stalk, which was characterized as the highly-porous nanocarbon that is of the largest specific surface area at 1697.34 m2/g and 2-fold higher dyes adsorption. Notably, this nanocarbon enabled to eliminate the most toxic compounds released from CaO pretreatment and enzymatic hydrolysis, and also showed much improved electrochemical performance with specific capacitance at 205 F/g. Hence, this work has raised a mechanism model to interpret how the recalcitrance-reduced lignocellulose is convertible for high-yield bioethanol and multiple-function biochar with high performance.

Complex roles for sulfation in the toxicities of polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are persistent organic toxicants derived from legacy pollution sources and their formation as inadvertent byproducts of some current manufacturing processes. Metabolism of PCBs is often a critical component in their toxicity, and relevant metabolic pathways usually include their initial oxidation to form hydroxylated polychlorinated biphenyls (OH-PCBs). Subsequent sulfation of OH-PCBs was originally thought to be primarily a means of detoxication; however, there is strong evidence that it may also contribute to toxicities associated with PCBs and OH-PCBs. These contributions include either the direct interaction of PCB sulfates with receptors or their serving as a localized precursor for OH-PCBs. The formation of PCB sulfates is catalyzed by cytosolic sulfotransferases, and, when transported into the serum, these metabolites may be retained, taken up by other tissues, and subjected to hydrolysis catalyzed by intracellular sulfatase(s) to regenerate OH-PCBs. Dynamic cycling between PCB sulfates and OH-PCBs may lead to further metabolic activation of the resulting OH-PCBs. Ultimate toxic endpoints of such processes may include endocrine disruption, neurotoxicities, and many others that are associated with exposures to PCBs and OH-PCBs. This review highlights the current understanding of the complex roles that PCB sulfates can have in the toxicities of PCBs and OH-PCBs and research on the varied mechanisms that control these roles.

UPLC-Q-TOF-MS/MS-based urine metabolomics studies on the toxicity and detoxication of Tripterygium wilfordii Hook. f. after roasting.

Tripterygium wilfordii (TW), a well-known traditional Chinese medicine, was widely used in the treatment of autoimmune disorders and inflammatory diseases. However, the clinical use of TW was limited by severe toxicities, such as hepatotoxicity and nephrotoxicity. Our previous studies indicated that roasting was an effective approach for reducing TW-induced toxicity. After roasting, celastrol was completely decomposed, partially converted into 1-hydroxy-2,5,8-trimethyl-9-fluorenone and the total alkaloids content were significantly reduced. However, the detoxication mechanisms of roasting on TW were poorly unknown. This study aimed to explore the toxicity and detoxification mechanisms of TW after roasting based on urine metabolomics. Promising biomarkers were evaluated by multiple comparison analyses. Sixteen toxicity biomarkers were identified between control group and total extract group. Twelve toxicity biomarkers were identified between control group and total alkaloids group. Eight toxicity biomarkers were identified between control group and celastrol group. These metabolites were mainly involved in seven metabolic pathways, summarized as pentose and glucuronate interconversions, lipid metabolism (sphingolipid metabolism, glycerophospholipid metabolisms, fatty acid biosynthesis and steroid hormone biosynthesis) and amino acid metabolism (taurine and hypotaurine metabolism, tryptophan metabolism). After roasting, the toxicities of total extract, total alkaloids and celastrol were relieved by ameliorative serum parameters and pathological changes in hepatic and renal tissues which revealed that the reduction of celastrol and total alkaloids played important roles in the detoxification of roasting on TW. Furthermore, roasting regulated the levels of fourteen potential biomarkers in the total extract group, ten potential biomarkers in the total alkaloids group and seven candidate biomarkers in the celastrol group to normal levels. Biological pathway analysis revealed that roasting may ameliorate TW-induced metabolic disorders in pentose and glucuronate interconversions, lipid metabolism and amino acid metabolism. This study provided evidence for the application of roasting in TW.

The effect of silica-magnetite nanoparticles on the ecotoxicity of the antibiotic ciprofloxacin.

The increase in the production and application of engineered nanomaterials, including nanoparticles (NPs), leads to their discharge into the environment, where they can interact with coexisting antibiotics from wastewater, causing a complicated joint effect on organisms that need to be studied. Herein, a typical engineered nanomaterial, silica-magnetite NPs modified with tetraethoxysilane and 3-aminopropyltriethoxysilane (MTA-NPs, 1-2 g/L), and common antibiotic ciprofloxacin (CIP, 0-5 mg/L) were selected as the analytes. Their joint toxicity to a model of ciliates infusoria, Paramecium caudatum was specifically investigated. The impact of CIP, MTA-NPs, and humic acids (HA) was tracked for 24 h, individually and collectively, on the mortality of infusoria. The addition of MTA-NPs and HA at the studied concentrations leads to 40% mortality of organisms. The combined presence of the MTA-NPs at a concentration of 1.5-2 mg/L and HA at a concentration of 20-45 mg/L has a multiplier effect and allows to reduce the mortality rate of ciliates > 30% due to the enhanced removal of CIP. That finding demonstrated a clearly detoxifying role of dissolved organic matter (here, humic substances) in case of complex water pollution where pharmaceuticals and nanomaterials are presented.

The loss of Halloween gene function seriously affects the development and reproduction of Diaphorina citri (Hemiptera: Liviidae) and increases its susceptibility to pesticides.

The citrus industry has suffered severe losses as a result of Huanglongbing spread by Diaphorina citri. Controlling the population of D. citri is the key to preventing and controlling the spread of Huanglongbing. Ecdysteroids are key hormones that regulate insect development and reproduction. Therefore, the Halloween gene family involved in the ecdysone synthesis of D. citri is an ideal target for controlling the population growth of this insect. In this study, we successfully cloned four Halloween genes expressed during D. citri development. Silencing of one of the four genes resulted in a significant decrease in 20E titers in nymphs and significant decreases in the developmental, survival and emergence rates. Inhibiting Halloween gene expression in adults impeded the growth of the female ovary, diminished yolk formation, lowered vitellogenin transcription levels, and hence impaired female fecundity. This showed that Halloween genes were required for D. citri development and reproduction. DcCYP315A1 and DcCYP314A1 were highly expressed when D. citri was exposed to thiamethoxam and cypermethrin, and silencing these two genes made D. citri more sensitive to these two pesticides. Inhibition of DcCYP315A1 and DcCYP314A1 expression not only significantly delayed the development and reproduction of D. citri but also increased its susceptibility to pesticides. Therefore, these two genes are more suitable as potential target genes for controlling D. citri.

Quinoline is more genotoxic than 4-methylquinoline in hiHeps cells and rodent liver.

Environmental pollutants, such as quinoline (QN) and 4-methylquinoline (4-MeQ), may be genotoxic and carcinogenic. Earlier studies, including in vitro genotoxicity tests, indicated that 4-MeQ is more mutagenic than QN. However, we hypothesized that the methyl group of 4-MeQ favors detoxication over bioactivation, and this factor may be overlooked in in vitro tests that do not incorporate supplementation with cofactors for enzymes that catalyze conjugation reactions. We used human induced hepatocyte cells (hiHeps), which express such enzymes, and compared the genotoxicity of 4-MeQ and QN. We also carried out an in vivo micronucleus (MN) test in rat liver, since 4-MeQ is not genotoxic in rodent bone marrow. In the Ames test and the Tk gene mutation assay, with rat S9 activation, 4-MeQ was more mutagenic than QN. However, QN induced significantly higher MN frequencies in hiHeps and rat liver than did 4-MeQ. Furthermore, QN upregulated genotoxicity marker genes much more than did 4-MeQ. We also investigated the roles of two important detoxication enzymes, UDP-glucuronosyltransferases (UGTs) and cytosolic sulfotransferases (SULTs). When hiHeps were preincubated with hesperetin (UGT inhibitor) and 2,6-dichloro-4-nitrophenol (SULT inhibitor), MN frequencies were elevated approximately 1.5-fold for 4-MeQ, whereas no significant effects were seen for QN. This study shows that QN is more genotoxic than 4-MeQ, when the roles of SULTs and UGTs in detoxication are considered and our results may improve understanding the structure-activity relationships of quinoline derivatives.

Research Progress on the Action Mechanism of Herbicide Safeners: A Review.

Herbicide safeners are agricultural chemicals that protect crops from herbicide injury and improve the safety of herbicides and the effectiveness of weed control. Safeners induce and enhance the tolerance of crops to herbicides through the synergism of multiple mechanisms. The principal mechanism is that the metabolic rate of the herbicide in the crop is accelerated by safeners, resulting in the damaging concentration at the site of action being reduced. We focused on discussing and summarizing the multiple mechanisms of safeners to protect crops in this review. It is also emphasized how safeners alleviate herbicide phytotoxicity to crops by regulating the detoxification process and conducting perspectives on future research on the action mechanism of safeners at the molecular level.

Reversibility and Low Commitment to Forward Catalysis in the Conjugation of Lipid Alkenals by Glutathione Transferase A4-4.

High concentrations of electrophilic lipid alkenals formed during oxidative stress are implicated in cytotoxicity and disease. However, low concentrations of alkenals are required to induce antioxidative stress responses. An established clearance pathway for lipid alkenals includes conjugation to glutathione (GSH) via Michael addition, which is catalyzed mainly by glutathione transferase isoform A4 (GSTA4-4). Based on the ability of GSTs to catalyze hydrolysis or retro-Michael addition of GSH conjugates, and the antioxidant function of low concentrations of lipid alkenals, we hypothesize that GSTA4-4 contributes a homeostatic role in lipid metabolism. Enzymatic kinetic parameters for retro-Michael addition with trans-2-Nonenal (NE) reveal the chemical competence of GSTA4-4 in this putative role. The forward GSTA4-4-catalyzed Michael addition occurs with the rapid exchange of the C2 proton of NE in D2O as observed by NMR. The isotope exchange was completely dependent on the presence of GSH. The overall commitment to catalysis, or the ratio of first order kcat,f for 'forward' Michael addition to the first order kcat,ex for H/D exchange is remarkably low, approximately 3:1. This behavior is consistent with the possibility that GSTA4-4 is a regulatory enzyme that contributes to steady-state levels of lipid alkenals, rather than a strict 'one way' detoxication enzyme.

The overlooked functions of trichomes: Water absorption and metal detoxication.

Trichomes are epidermal outgrowths on plant shoots. Their roles in protecting plants against herbivores and in the biosynthesis of specialized metabolites have long been recognized. Recently, studies are increasingly showing that trichomes also play important roles in water absorption and metal detoxication, with these roles having important implications for ecology, the environment, and agriculture. However, these two functions of trichomes have been largely overlooked and much remains unknown. In this review, we show that the trichomes of 37 plant species belonging to 14 plant families are involved in water absorption, while the trichomes of 33 species from 13 families are capable of sequestering metals within their trichomes. The ability of trichomes to absorb water results from their decreased hydrophobicity compared to the remainder of the leaf surface as well as the presence of special structures for collecting and absorbing water. In contrast, the metal detoxication function of trichomes results not only from the good connection of their basal cells to the underlying vascular tissues, but also from the presence of metal-chelating ligands and transporters within the trichomes themselves. Knowledge gaps and critical future research questions regarding these two trichome functions are highlighted. This review improves our understanding on trichomes.

Mechanism of macroalgae Gracilaria bailiniae responding to cadmium and lanthanum.

Macroalgae can accumulate a wide array of metals, leading to their appliance as biomonitors of aquatic environments. With the rapid development of industrial and agricultural-based activities, Cd pollution in aquatic environments is considered an increasingly severe problem worldwide. Although La could alleviate the Cd stress in higher terrestrial plants, the response mechanisms of macroalgae to Cd and La are unknown. Along these lines, in this work, Cd significantly affected the growth, internal cellular structure, photosynthesis, pigment content, antioxidant enzyme activity, and lipid peroxidation level of G. bailiniae. However, the presence of La alleviated these adverse effects from Cd. Furthermore, the response mechanism of G. bailiniae to Cd was attributed to the self-antioxidant ability enhancement, membrane defense, and programmed-cellular regulation. However, the presence of La mediated the biosynthesis of both flavonoids and lipids, which inhibited the Cd accumulation, modulated algal stress signalling networks, renewed the impaired chlorophyll molecule, maintained the activity of the crucial enzyme, enhanced antioxidant ability, and maintained the stabilization of redox homeostasis, alleviating the adverse impact from Cd and improve the growth of G. bailiniae. The experimental results successfully demonstrate a new detoxicant to alleviate Cd stress, promoting a more comprehensive array of macroalgal applications.

Detoxication and bioconversion of aflatoxin B1 by yellow mealworms (Tenebrio molitor): A sustainable approach for valuable larval protein production from contaminated grain.

Yellow mealworm (Tenebrio molitor) is a supplementary protein source for food and feed and represents a promising solution to manage grain contaminated with Aflatoxin B1 (AFB1). In this study, AFB1 present in different concentrations in wheat bran was treated and removed via bioconversion by yellow mealworm of different instars, with emphasis on the bioconversion performance and metabolism of AFB1. Upon application of wheat bran spiked with 100 µg/kg AFB1 to 5th-6th instar yellow mealworms, the conversion rate of AFB1 was up to 87.85 %. Low level of AFB1 (< 2 µg/kg) was accumulated in the larval bodies, and the survival rate, development and nutrition contents of yellow mealworm were not significantly affected. It was revealed that 1 kg of wheat bran contaminated with AFB1 increased the weight of yellow mealworms from 138 g to 469 g, containing approximately 103 g of protein. The bioconversion of AFB1 by yellow mealworms led to generation of 13 metabolites in the frass and 3 metabolites in the larvae. AFB1 was detoxicated and removed via phase I metabolism comprising reduction, dehydrogenation, hydration, demethylation, hydroxylation, decarbonylation and ketoreduction, followed by phase II metabolism involving conjugation of amino acid, glucoside and glutathione (GSH). The toxicity of AFB1 metabolites was deemed lower than that of AFB1 according to their structures. This study provides a sustainable approach and theoretical foundation on using yellow mealworms for cleaner grain contamination management and valuable larval protein production via bioconversion of food and feed contaminated by AFB1.

A Multi-Omics Study of Familial Lung Cancer: Microbiome and Host Gene Expression Patterns.

Background: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links. Methods: Tissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics. Results: Our FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system. Conclusions: The lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.

A New Insight into Toxicity of Colchicine Analogues by Molecular Docking Analysis Based on Intestinal Tight Junction Protein ZO-1.

Colchicine (COL) is a well-known plant alkaloid long used for medical purposes due to the selective anti-inflammatory effect on acute gouty arthritis. It is also a kind of mitosis toxin with strong inhibitory effects of cell division and is therefore being applied to the treatment of various cancers. However, this product shows a variety of adverse effects that are significantly correlated with the dosage and have attracted much attention. For the first time, the present work obtained a new insight into the gastrointestinal toxicity of colchicine analogues by molecular docking analysis, which was based on the 3D structure of intestinal tight junction protein ZO-1 and the ligand library containing dozens of small-molecule compounds with the basic skeleton of COL and its metabolites. The binding energy and mode of protein-ligand interaction were investigated to better understand the structure-toxicity relationships of COL analogues and the mechanism of action as well. Cluster analysis clearly demonstrated the strong correlation between the binding energy and toxicity of ligand molecules. The interaction mode further revealed that the hydrogen bonding (via the C-7 amide or C-9 carbonyl group) and hydrophobic effect (at ring A or C) were both responsible for ZO-1-related gastrointestinal toxicity of COL analogues, while metabolic transformation via phase I and/or phase II reaction would significantly attenuate the gastrointestinal toxicity of colchicine, indicating an effective detoxication pathway through metabolism.

Investigation on detoxication effects of 2-hydroxypropyl-ß-cyclodextrin over two halogenated aromatic DBPs 2,4,6-trichlorophenol and 2,4,6-tribromophenol binding with human serum albumin.

The health effects of disinfection byproducts (DBPs) in drinking water drew great attention recently. Herein, by using in vitro (fluorescence quenching, UV absorbance, circular dichroism) and in silico (molecular docking) method, binding interactions of two halophenolic DBPs (2,4,6-trichlorophenol [TCP] and 2,4,6-tribromophenol [TBP]) with human serum albumin (HSA) and the influence of hydroxypropyl-beta-cyclodextrin (HPCD) on the interactions were investigated. TCP/TBP could form complexes with HSA mainly by hydrogen bonding, while changing its secondary structure, among which TBP showed more influential effect. Interestingly, the binding constants for halophenol-HSA complexes decreased obviously with the involvement of HPCD. Molecular docking results revealed that HPCD could include TCP/TBP into its cavity and change their original binding sites from subdomain IB to IIA, resulting in a more stable binding system. These findings are beneficial for understanding the toxicity of halophenols inside the human body and indicated that HPCD could be a promising detoxication agent for DBPs.

Progress in Traditional Chinese Medicine Against Respiratory Viruses: A Review.

Respiratory viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-1, SARS-CoV-2, influenza A viruses, and respiratory syncytial virus, pose a serious threat to society. Based on the guiding principles of "holism" and "syndrome differentiation and treatment", traditional Chinese medicine (TCM) has unique advantages in the treatment of respiratory virus diseases owing to the synergistic effect of multiple components and targets, which prevents drug resistance from arising. According to TCM theory, there are two main strategies in antiviral treatments, namely "dispelling evil" and "fu zheng". Dispelling evil corresponds to the direct inhibition of virus growth and fu zheng corresponds to immune regulation, inflammation control, and tissue protection in the host. In this review, current progress in using TCMs against respiratory viruses is summarized according to modern biological theories. The prospects for developing TCMs against respiratory viruses is discussed to provide a reference for the research and development of innovative TCMs with multiple components, multiple targets, and low toxicity.

Roles of cation efflux pump in biomineralization of cadmium into quantum dots in Escherichia coli.

Cadmium (Cd) is a typical and widely present toxic heavy metals in environments. Biomineralization of Cd ions could alleviate the toxicity and produce valuable products in certain waste streams containing selenite. However, the impact of the intrinsic Cd(II) efflux system on the biotransformation process remains unrevealed. In this work, the significance of the efflux system on Cd biomineralization was evaluated by constructing engineered Escherichia coli strains, including ΔzntA with suppressed Cd(II) efflux system and pYYDT-zntA with strengthened Cd(II) efflux system. Compared to the wild type (WT), 20% more Cd ions were accumulated in ΔzntA and 17% less were observed in pYYDT-zntA in the presence of selenite as determined by inductively coupled plasma atomic emission spectrometer. Through combination with X-ray absorption fine structure analysis, it was discovered that 50% higher production of CdSxSe1-x quantum dots (QDs) was achieved in the ΔzntA cells than that in the WT cells. Moreover, the ΔzntA cells exhibited the same viability as the WT cells and the pYYDT-zntA cells because accumulated Cd ions were transformed into biocompatible QDs. In addition, the biosynthesized QDs had a uniform particle size (3.82 ± 0.53 nm) and a long fluorescence lifetime (45.6 ns), which could potentially be utilized for bio-imaging. These results not only elucidate the significance of Cd(II) efflux system in the biotransformation of Cd ions and selenite, but also provide a promising way to recover Cd and Se as valuable products in certain waste streams.

Structural and functional analysis of the inhibition of equine glutathione transferase A3-3 by organotin endocrine disrupting pollutants.

Organotin compounds are highly toxic environmental pollutants with neurotoxic and endocrine-disrupting effects. They are potent inhibitors of glutathione transferases (GSTs), thus impeding their detoxication and antioxidant functions. Several GSTs, including equine GST A3-3 (EcaGST A3-3), exhibit steroid double-bond isomerase activity and are involved in the biosynthesis of testosterone and progesterone. We have performed enzyme kinetics analyses of the inhibition of EcaGST A3-3 by organotin compounds. We have also solved crystal structures of EcaGST A3-3 in complexes with glutathione, and with glutathione together with covalently bound triethyltin. Our structural data indicate that the tin atom forms strong bonds with a covalent character not only with the glutathione, but also with a tyrosyl residue of the enzyme itself, thereby preventing the release of the glutathione-organotin adduct and completely blocking the enzyme function. This work presents a structural basis for the general mechanism of GST inhibition by organotin compounds and contributes to the understanding of their neurotoxic and endocrine disrupting effects.

A polyphenol-rich cranberry extract protects against endogenous exposure to persistent organic pollutants during weight loss in mice.

The dramatic rise in the global occurrence of obesity and associated diseases calls for new strategies to promote weight loss. However, while the beneficial effects of weight loss are well known, rapid loss of fat mass can also lead to the endogenous release of liposoluble molecules with potential harmful effects, such as persistent organic pollutants (POP). The aim of this study was to evaluate the impact of a polyphenol-rich cranberry extract (CE) on POP release and their potential deleterious effects during weight loss of obese mice. C57BL/6 J mice were fed an obesogenic diet with or without a mixture of POP for 12 weeks and then changed to a low-fat diet to induce weight loss and endogenous POP release. The POP-exposed mice were then separated in two groups during weight loss, receiving either CE or the vehicle. Unexpectedly, despite the higher fat loss in the CE-treated group, the circulating levels of POP were not enhanced in these mice. Moreover, glucose homeostasis was further improved during CE-induced weight loss, as revealed by lower fasting glycemia and improved glucose tolerance as compared to vehicle-treated mice. Interestingly, the CE extract also induced changes in the gut microbiota after weight loss in POP-exposed mice, including blooming of Parvibacter, a member of the Coriobacteriaceae family which has been predicted to play a role in xenobiotic metabolism. Our data thus suggests that the gut microbiota can be targeted by polyphenol-rich extracts to protect from increased POP exposure and their detrimental metabolic effects during rapid weight loss.

[Detoxification mechanism of Aconiti Lateralis Radix Praeparata combined with dried Rehmanniae Radix based on metabolic enzymes in liver].

The enzymes CYP1 A2 and CYP3 A4 were measured by building a "Cocktail" probe drug and the incubation system of liver microsomes. The compatibility of Aconiti Lateralis Radix Praeparata combined with dried Rehmanniae Radix on CYP450 enzyme protein and gene expression was explored from the level of protein and molecular biology. It explored the molecular mechanism of compatibility detoxication of Aconiti Lateralis Radix Praeparata to provide scientific support for clinical safe and effective application of Aconiti Lateralis Radix Praeparata. The CYP450 enzyme activity was determined by using "Cocktail" probe drugs. The content of CYP450 enzyme was measured by CO reduction of differential spectrum method. The mRNA expression of CYP1 A2 and CYP3 A4 enzyme was detected by RT-PCR technology. Compared with the blank group, the CYP1 A2 and CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group with significant differences(P<0.05), while the CYP3 A4 enzyme activity and mRNA expression were no influence in the Aconiti Lateralis Radix Praeparata group. The CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The content of CYP450 enzyme was decreased in the Aconiti Lateralis Radix Praeparata group, contributed to extremely significant difference(P<0.01). The content of CYP450 enzyme was increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The CYP1 A2 and CYP3 A4 enzyme activity and gene expression were enhanced after dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata. The metabolism of toxic ingredients of Aconiti Lateralis Radix Praeparata was accelerated to reach an effect of detoxication. The detoxication mechanism of compatibility of Aconiti Lateralis Radix Praeparata was verified from the viewpoint of liver metabolic enzymes.