Chrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex.

BACKGROUND: Expression of the KITENIN/ErbB4 oncogenic complex is associated with metastasis of colorectal cancer to distant organs and lymph nodes and is linked with poor prognosis and poor survival. METHODS: Here, we used in vitro and in silico methods to test the ability of chrysophanol, a molecule of natural origin, to suppress the progression of colorectal cancer by targeting the KITENIN/ErbB4 complex. RESULTS: Chrysophanol binds to ErbB4, disrupting the ErbB4/KITENIN complex and causing autophagic degradation of KITENIN. We demonstrated that chrysophanol binds to ErbB4 according to a molecular docking model. Chrysophanol reversed KITENIN-mediated effects on cell motility, aerobic glycolysis, and expression of downstream effector genes. Moreover, under conditions of KITENIN overexpression, chrysophanol suppressed the production of onco-metabolites. CONCLUSION: Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Unveiling Anthraquinones: Diverse Health Benefits of an Essential Secondary Metabolite.

Since ancient times, plants have been used as a remedy for numerous diseases. The pharmacological properties of plants are due to the presence of secondary metabolites like terpenoids, flavonoids, alkaloids, etc. Anthraquinones represent a group of naturally occurring quinones found generously across various plant species. Anthraquinones attract a significant amount of attention due to their reported efficacy in treating a wide range of diseases. Their complex chemical structures, combined with inherent medicinal properties, underscore their potential as agents for therapy. They demonstrate several therapeutic properties such as laxative, antitumor, antimalarial, antibacterial, antifungal, antioxidant, etc. Anthraquinones are found in different forms (derivatives) in plants, and they exhibit various medicinal properties due to their structure and chemical nature. The precursors for the biosynthesis of anthraquinones in higher plants are provided by different pathways such as plastidic hemiterpenoid 2-C-methyl-D-erthriol4-phosphate (MEP), mevalonate (MVA), isochorismate synthase and polyketide. By conducting a thorough analysis of scientific literature, this review provides insights into the intricate interplay between anthraquinone biosynthesis and its broad-ranging contributions to human health.

AQDS-functionalized biochar enhances the bioreduction of Cr(VI) by Shewanella putrefaciens CN32.

The bioreduction of toxic chromium(VI) to sparingly soluble chromium(III) represents an environmentally friendly and cost-effective method for remediating Cr contamination. Usually, this bioreduction process is slow and requires the addition of quinone compounds as electron shuttles to enhance the reaction rate. However, the dissolved quinone compounds are susceptible to loss with water flow, thereby limiting their effectiveness. To address this challenge, this study loaded anthraquinone-2,6-disulfonate (AQDS), a typical quinone compound, onto biochar (BC) to create a novel solid-phase electron mediator (BC-AQDS) that can sustainably promote Cr(VI) bioreduction. The experimental results demonstrated that BC-AQDS significantly promoted the bioreduction of Cr(VI), where the reaction rate constant increased by 4.81 times, and the reduction extent increased by 38.31%. X-ray photoelectron spectroscopy and Fourier-Transform Infrared Spectroscopy analysis revealed that AQDS replaced the -OH functional groups on the BC surface to form BC-AQDS. Upon receiving electrons from Shewanella putrefaciens CN32, BC-AQDS was reduced to BC-AH2DS, which subsequently facilitated the reduction of Cr(VI) to Cr(III). This redox cycle between BC-AQDS and BC-AH2DS effectively enhanced the bioreduction rate of Cr(VI). Our study also found that a lower carbonization temperature of BC resulted in a higher surface -OH functional group content, enabling a greater load of AQDS and a more pronounced enhancement effect on the bioreduction of Cr(VI). Additionally, a smaller particle size of BC and a higher dosage of BC-AQDS further contributed to the enhancement of Cr(VI) bioreduction. The preparation of BC-AQDS in this study effectively improve the utilization of quinone compounds and offer a promising approach for enhancing the bioreduction of Cr(VI). It provides a more comprehensive reference for understanding and solving the problem of Cr pollution in groundwater.

Scorch processing of rhubarb (Rheum tanguticum Maxim. ex Balf.) pyrolyzed anthraquinone glucosides into aglycones and improved the therapeutic effects on thromboinflammation via regulating the complement and coagulation cascades pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The pathophysiological mechanism of thromboinflammation involves the intricate interplay between the inflammatory responses and coagulation cascades. Rhubarb is frequently used in traditional Chinese medicine to treat thromboinflammatory diseases. The scorched rhubarb (prepared by stir-baking the dried raw rhubarb till it partly turns to charcoal) is believed to possess enhanced blood-cooling and stasis-removing functions compared to the raw rhubarb, thereby augmenting the therapeutic effects on thromboinflammation. AIM OF THE STUDY: This study aimed to explore the chemical and pharmacological foundations of the scorch processing of rhubarb in order to ensure and enhance the efficacy and safety of the scorched rhubarb for treating thromboinflammatory diseases. MATERIALS AND METHODS: The dried raw rhubarb pieces were subjected to stir-baking at 180 °C for 10∼80 min to obtain the rhubarbs with varying degrees of scorching. Typical ingredients present in rhubarb pieces and extracts were determined by high-performance liquid chromatography. The therapeutic effects of the raw and scorched rhubarb on thromboinflammation were evaluated using a rat model. Proteomics analysis was employed to screen potential biological pathways associated with thromboinflammation treatment by the raw and scorched rhubarb, which were further verified using a cell model. RESULTS: Morphological properties indicated that the rhubarb baked at 180 °C for 50 min in this research showed the optimal degree of scorching. Compared to the raw rhubarb, the properly scorched rhubarb exhibited lower levels of anthraquinone glucosides, higher levels of anthraquinone aglycones, superior anti-thromboinflammatory effects, and no purgative side effects. Proteomics analysis revealed that the complement and coagulation cascades pathway played a significant role in mediating the therapeutic effects of the raw and scorched rhubarb on thromboinflammation. Furthermore, it was found that anthraquinone aglycones were more effective than their glucoside counterparts in restoring the impaired vascular endothelial cells as well as regulating the complement and coagulation cascades pathway. CONCLUSIONS: Proper scorch processing may augment the therapeutic effects of rhubarb on thromboinflammation via relieving inflammation and oxidative stress, repairing vascular endothelial cells, restoring coagulation cascades and blood rheology, and regulating some other biological processes. This may be partly caused by the scorch-induced thermolysis of anthraquinone glucosides into their aglycone counterparts that seemed to perform better in regulating the complement and coagulation cascades pathway.

In Vitro Toxicity Assessment of Cortinarius sanguineus Anthraquinone Aglycone Extract.

Biocolourants could be a sustainable option for dyes that require fossil-based chemicals in their synthesis. We studied the in vitro toxicity of anthraquinone aglycone extract obtained from Cortinarius sanguineus fungus and compared it to the toxicity of its two main components, emodin and previously studied dermocybin. Cell viability, cytotoxicity, and oxidative stress responses in HepG2 liver and THP-1 immune cell lines were studied along with skin sensitisation. In addition, genotoxicity was studied with comet assay in HepG2 cells. Cellular viability was determined by MTT, propidium iodide, and lactate dehydrogenase assays, which showed that the highest doses of both the aglycone extract and emodin affected the viability. However, the effect did not occur in all of the used assays. Notably, after both exposures, a dose-dependent increase in oxidative stress factors was observed in both cell lines as measured by MitoSOX and dihydroethidium assays. C. sanguineus extract was not genotoxic in the comet assay. Importantly, both emodin and the extract activated the skin sensitisation pathway in the KeratinoSens assay, suggesting that they can induce allergy in humans. As emodin has shown cytotoxic and skin-sensitising effects, it is possible that the adverse effects caused by the extract are also mediated by it since it is the main component present in the fungus.

Comprehensive identification strategy for rapid profiling of chemical constituents using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry with Rhubarb as an example.

In this study, the collision induced dissociation tandem mass spectrometry (CID-MS/MS) fragmentation pathway of chemical components in rhubarb was wholly explored using 34 standards by UHPLC-QTOF-MS/MS in negative ion mode. In consequently, the diagnostic product ions for speedy screening and categorization of chemical components in rhubarb were ascertained based on their MS/MS splitting decomposition patterns and intensity analysis. According to these findings, a fresh two-step data mining strategy had set up. The initial key step involves the use of characteristic product ions and neutral loss to screen for different types of substituents and basic skeletons of compounds. The subsequent key step is to screen and classify different types of compounds based on their characteristic product ions. This method can be utilized for rapid research, classification, and identification of compounds in rhubarb. A total of 356 compounds were rapidly identified or tentatively characterized in three rhubarb species extracts, including 150 acylglucoside, 125 anthraquinone, 65 flavanols and 15 other compounds. This study manifests that the analytical strategy is feasible for the analysis of complex natural products in rhubarb.

The Anthraquinone Derivative C2 Enhances Oxaliplatin-Induced Cell Death and Triggers Autophagy via the PI3K/AKT/mTOR Pathway.

Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and apoptosis-related proteins, whereas its underlying mechanism remains unclear. A notable aspect of this study is how C2 overcomes the multidrug susceptibility of HCT116/L-OHP, a colon cancer cell line that is resistant to both in vitro and in vivo oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP). In a xenograft tumor mouse model, we discovered that the mixture of C2 and L-OHP reversed the resistance of HCT116/L-OHP cells to L-OHP and inhibited tumor growth; furthermore, C2 down-regulated the gene expression levels of P-gp and BCRP and decreased P-gp's drug efflux activity. It is important to note that while C2 re-sensitized the HCT116/L-OHP cells to L-OHP for apoptosis, it also triggered a protective autophagic pathway. The expression levels of cleaved caspase-3 and Beclin 1 steadily rose. Expression of PI3K, phosphorylated AKT, and mTOR were decreased, while p53 increased. We demonstrated that the anthraquinone derivative C2 acts as an L-OHP sensitizer and reverses resistance to L-OHP in HCT116/L-OHP cells. It suggests that C2 can induce autophagy in HCT116/L-OHP cells by mediating p53 and the PI3K/AKT/mTOR signaling pathway.

The occurrence and bioactivity of tetrahydronaphthoquinoline-diones (THNQ-dione).

Natural products have been important in the discovery of new drugs, but their use is limited due to issues with accessibility and synthesis. Tetrahydronaphthoquinoline-dione (THNQ-dione) is a key structural feature found in several natural and synthetic compounds that exhibit notable biological properties. The unique properties of THNQ-diones can be attributed to the fusion of tetrahydroquinoline and anthraquinone moieties. These alkaloids are synthesised through various biosynthetic pathways, leading to diverse structures and bioactivities. Despite their significance, THNQ-diones have not been extensively covered in the review literature, highlighting the importance of this article in discussing their natural occurrence and biological activities. This article explores the distribution of THNQ-dione alkaloids in different organisms and their potential as a source of novel bioactive natural products.

Novel anthraquinone amide derivatives as potential glyoxalase-I inhibitors.

This study aimed to identify novel Glyoxalase-I (Glo-I) inhibitors with potential anticancer properties, focusing on anthraquinone amide-based derivatives. We synthesized a series of these derivatives and conducted in silico docking studies to predict their binding interactions with Glo-I. In vitro assessments were performed to evaluate the anti-Glo-I activity of the synthesized compounds. A comprehensive structure-activity relationship (SAR) analysis identified key features responsible for specific binding affinities of anthraquinone amide-based derivatives to Glo-I. Additionally, a 100 ns molecular dynamics simulation assessed the stability of the most potent compound compared to a co-crystallized ligand. Compound MQ3 demonstrated a remarkable inhibitory effect against Glo-I, with an IC50 concentration of 1.45 µM. The inhibitory potency of MQ3 may be attributed to the catechol ring, amide functional group, and anthraquinone moiety, collectively contributing to a strong binding affinity with Glo-I. Anthraquinone amide-based derivatives exhibit substantial potential as Glo-I inhibitors with prospective anticancer activity. The exceptional inhibitory efficacy of compound MQ3 indicates its potential as an effective anticancer agent. These findings underscore the significance of anthraquinone amide-based derivatives as a novel class of compounds for cancer therapy, supporting further research and advancements in targeting the Glo-I enzyme to combat cancer.

Evaluation of oyster mushroom (Pleurotus ostreatus)-derived anthraquinone on the induction of apoptosis and suppression of MMP-2 and MMP-9 expression in breast cancer cells.

Introduction: Breast cancer results from tissue degradation caused by environmental and genetic factors that affect cells in the body. Matrix metalloproteinases, such as MMP-2 and MMP-9, are considered potential putative markers for tumor diagnosis in clinical validation due to their easy detection in body fluids. In addition, recent reports have suggested multiple roles for MMPs, rather than simply degeneration of the extracellular matrix, which comprises mobilizing growth factors and processing surface molecules. Methods: In this study, the chemotherapeutic effects of anthraquinone (AQ) extracted from edible mushrooms (Pleurotus ostreatus Jacq. ex Fr.) cells was examined in MCF-7 breast cancer cells. The cytotoxic potential and oxidative stress induced by purified anthraquinone were assessed in MCF-7 cells using MTT and ROS estimation assays. Gelatin Zymography, and DNA fragmentation assays were performed to examine MMP expression and apoptotic induction in the MCF-7 cells treated with AQ. The genes crucial for mutations were examined, and the mutated RNA knockout plausibility was analyzed using the CRISPR spcas9 genome editing software. Results: MCF-7 cells were attenuated in a concentration-dependent manner by the administration of AQ purified from P. ostreatus compared with the standard anticancer drug paclitaxel. AQ supplementation decreased oxidative stress and mitochondrial impairment in MCF-7 cells. Treatment with AQ and AQ with paclitaxel consistently decreased the expression of crucial marker genes such as MMP2 and MMP9. The mutated genes MMP2, MMP7, and MMP9 were assessed and observed to reveal four putative gene knockdown potentials for breast cancer treatment. Conclusions: The synergistic application of AQ and paclitaxel exerted a strong inhibitory effect on the MCF-7 breast cancer cells. Extensive studies are imperative to better understand the action of bioactive mixes on the edible oyster fungus P. ostreatus. The gene knockout potential detected by CRISPR SpCas9 will aid in elite research into anticancer treatments.

Combinatorial metabolic engineering of Streptomyces sp. CB03234-S for the enhanced production of anthraquinone-fused enediyne tiancimycins.

BACKGROUND: Anthraquinone-fused enediynes (AFEs) are excellent payloads for antibody-drug conjugates (ADCs). The yields of AFEs in the original bacterial hosts are extremely low. Multiple traditional methods had been adopted to enhance the production of the AFEs. Despite these efforts, the production titers of these compounds are still low, presenting a practical challenge for their development. Tiancimycins (TNMs) are a class of AFEs produced by Streptomyces sp. CB03234. One of their salient features is that they exhibit rapid and complete cell killing ability against various cancer cell lines. RESULTS: In this study, a combinatorial metabolic engineering strategy guided by the CB03234-S genome and transcriptome was employed to improve the titers of TNMs. First, re-sequencing of CB03234-S (Ribosome engineered mutant strains) genome revealed the deletion of a 583-kb DNA fragment, accounting for about 7.5% of its genome. Second, by individual or combined inactivation of seven potential precursor competitive biosynthetic gene clusters (BGCs) in CB03234-S, a double-BGC inactivation mutant, S1009, was identified with an improved TNMs titer of 28.2 ± 0.8 mg/L. Third, overexpression of five essential biosynthetic genes, including two post-modification genes, and three self-resistance auxiliary genes, was also conducted, through which we discovered that mutants carrying the core genes, tnmE or tnmE10, exhibited enhanced TNMs production. The average TNMs yield reached 43.5 ± 2.4 mg/L in a 30-L fermenter, representing an approximately 360% increase over CB03234-S and the highest titer among all AFEs to date. Moreover, the resulting mutant produced TNM-W, a unique TNM derivative with a double bond instead of a common ethylene oxide moiety. Preliminary studies suggested that TNM-W was probably converted from TNM-A by both TnmE and TnmE10. CONCLUSIONS: Based on the genome and transcriptome analyses, we adopted a combined metabolic engineering strategy for precursor enrichment and biosynthetic pathway reorganization to construct a high-yield strain of TNMs based on CB03234-S. Our study establishes a solid basis for the clinical development of AFE-based ADCs.

Naphthoquinones and anthraquinones: Exploring their impact on acetylcholinesterase enzyme activity.

The identification of novel acetylcholinesterase inhibitors holds significant relevance in the treatment of Alzheimer's disease (AD), the prevailing form of dementia. The exploration of alternative inhibitors to the conventional acetylcholinesterase inhibitors is steadily gaining prominence. Quinones, categorized as plant metabolites, represent a specific class of compounds. In this study, the inhibitory effects of various naphthoquinone derivatives, along with anthraquinone and its derivatives, on the acetylcholinesterase (AChE) enzyme were investigated for this purpose. An in vitro investigation was conducted to examine the effects of these compounds in order to clarify the possible mechanism of inhibition in the interaction between the enzyme and chemicals. In addition, an in silico investigation was carried out to understand the conceivable inhibitor binding process to the enzyme's active site. The acquired outcomes corroborated the in vitro results. The AChE enzyme was found to be effectively inhibited by both naphthoquinones and anthraquinones, with inhibition constant (KI) values ranging from 0.014 to 0.123 µM (micormolar). The AChE enzyme was inhibited differently by this quinone and its derivatives. Although derivatives of naphthoquinone and anthraquinone exhibited a competitive inhibitory effect, derivatives of anthraquinone exhibited a noncompetitive inhibition effect. Furthermore, because it had the lowest KI value of any of these substances, 1,5-dihydroxyanthraquinone (1c) was shown to be the most potent inhibitor. The findings will add to the body of knowledge on the creation of fresh, potent, and successful treatment approaches.

Rhei Radix et Rhizoma and its anthraquinone derivatives: Potential candidates for pancreatitis treatment.

BACKGROUND: Pancreatitis is a common exocrine inflammatory disease of the pancreas and lacks specific medication currently. Rhei Radix et Rhizoma (RR) and its anthraquinone derivatives (AQs) have been successively reported for their pharmacological effects and molecular mechanisms in experimental and clinical pancreatitis. However, an overview of the anti-pancreatitis potential of RR and its AQs is limited. PURPOSE: To summarize and analyze the pharmacological effects of RR and its AQs on pancreatitis and the underlying mechanisms, and discuss their drug-like properties and future perspectives. METHODS: The articles related to RR and its AQs were collected from the Chinese National Knowledge Infrastructure, Wanfang data, PubMed, and the Web of Science using relevant keywords from the study's inception until April first, 2024. Studies involving RR or its AQs in cell or animal pancreatitis models as well as structure-activity relationship, pharmacokinetics, toxicology, and clinical trials were included. RESULTS: Most experimental studies are based on severe acute pancreatitis rat models and a few on chronic pancreatitis. Several bioactive anthraquinone derivatives of Rhei Radix et Rhizoma (RRAQs) exert local protective effects on the pancreas by maintaining pancreatic acinar cell homeostasis, inhibiting inflammatory signaling, and anti-fibrosis, and they improve systemic organ function by alleviating intestinal and lung injury. Pharmacokinetic and toxicity studies have revealed the low bioavailability and wide distribution of RRAQs, as well as hepatotoxicity and nephrotoxicity. However, there is insufficient research on the clinical application of RRAQs in pancreatitis. Furthermore, we propose effective strategies for subsequent improvement in terms of balancing effectiveness and safety. CONCLUSION: RRAQs can be developed as either candidate drugs or novel lead structures for pancreatitis treatment. The comprehensive review of RR and its AQs provides references for optimizing drugs, developing therapies, and conducting future studies on pancreatitis.

Utilization of carbon catabolite repression for efficiently biotransformation of anthraquinone O-glucuronides by Streptomyces coeruleorubidus DM.

Carbon catabolite repression (CCR) is a highly conserved mechanism that regulates carbon source utilization in Streptomyces. CCR has a negative impact on secondary metabolite fermentation, both in industrial and research settings. In this study, CCR was observed in the daunorubicin (DNR)-producing strain Streptomyces coeruleorubidus DM, which was cultivated in high concentration of carbohydrates. Unexpectedly, DM exhibited a high ability for anthraquinone glucuronidation biotransformation under CCR conditions with a maximum bioconversion rate of 95% achieved at pH 6, 30°C for 24 h. The co-utilization of glucose and sucrose resulted in the highest biotransformation rate compared to other carbon source combinations. Three novel anthraquinone glucuronides were obtained, with purpurin-O-glucuronide showing significantly improved water solubility, antioxidant activity, and antibacterial bioactivity. Comparative transcript analysis revealed that glucose and sucrose utilization were significantly upregulated as DM cultivated under CCR condition, which strongly enhance the biosynthetic pathway of the precursors Uridine diphosphate glucuronic acid (UDPGA). Meanwhile, the carbon metabolic flux has significantly enhanced the fatty acid biosynthesis, the exhaust of acetyl coenzyme A may lead to the complete repression of the biosynthesis of DNR, Additionally, the efflux transporter genes were simultaneously downregulated, which may contribute to the anthraquinones intracellular glucuronidation. Overall, our findings demonstrate that utilizing CCR can be a valuable strategy for enhancing the biotransformation efficiency of anthraquinone O-glucuronides by DM. This approach has the potential to improve the bioavailability and therapeutic potential of these compounds, opening up new possibilities for their pharmaceutical applications.

Anthraquinone/activated carbon electrochemical sensor and its application in acetaminophen analysis.

Acetaminophen (AC) can inhibit the synthesis of prostaglandins in the body, and has antipyretic and analgesic effects. In this paper, a two-step microwave impregnation method was used to prepare anthraquinone (AQ)-doped carbon composite, which were applied to the surface modification of glassy carbon electrodes (GCE) for the determination of acetaminophen (AC) using differential pulse voltammetry (DPV). The composites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman and Fourier infrared spectroscopy (FT-IR). The results showed that anthraquinone was successfully modified on the surface of activated carbon. The peak current of AC increased with its concentration in the range of 0.1 µM to 700 µM (R2 = 0.998) and a detection limit of 0.05 µM was obtained with 20%AQ doped carbon electrochemical sensor (20%AQ-C/GCE). Electrochemical Impedance Spectroscopy (EIS) test results indicated that the charge transfer resistance (Rct) of 20%AQ-C/GCE is only the one-fourth of that of bare GCE. The proposed 20%AQ-C/GCE sensor has good stability, reproducibility and selectivity for the detection of AC. The sensor is also suitable for the detection of real samples, indicating its good practicality.

Photodegradation enhances the toxic effect of anthracene on skin.

Anthracene, a polycyclic aromatic hydrocarbon (PAH), is a widespread environmental pollutant that poses potential risks to human health. Exposure to anthracene can result in various adverse health effects, including skin-related disorders. Photo exposure sufficiently removes the anthracene from the environment but also generates more degradation products which can be more toxic. The goal of this study was to assess the change in anthracene dermotoxicity caused by photodegradation and understand the mechanism of this change. In the present study, over 99.99% of anthracene was degraded within 24 h of sunlight exposure, while producing many intermediate products including 9,10-anthraquinone and phthalic acid. The anthracene products with different durations of photo exposure were applied to 2D and 3D human keratinocyte cultures. Although the non-degraded anthracene significantly delayed the cell migration, the cell viability and differentiation decreased dramatically in the presence of the photodegraded anthracene. Anthracene photodegradation products also altered the expression patterns of a number of inflammation-related genes in comparison to the control cells. Among these genes, il1a, il1b, il8, cxcl2, s100a9, and mmp1 were upregulated whereas the tlr4 and mmp3 were downregulated by the photodegraded anthracene. Topical deliveries of the photodegraded and non-degraded anthracene to the dorsal skin of hairless mice showed more toxic effects by the photodegraded anthracene. The 4-hour photodegradation products of anthracene thickened the epidermal layer, increased the dermal cellularity, and induced the upregulation of inflammatory markers, il1a, il1b, s100a9, and mmp1. In addition, it also prevented the production of a gap junction protein, Connexin-43. All the evidence suggested that photodegradation enhanced the toxicities of anthracene to the skin. The 4-hour photodegradation products of anthracene led to clinical signs similar to acute inflammatory skin diseases, such as atopic and contact dermatitis, eczema, and psoriasis. Therefore, the potential risk of skin irritation by anthracene should be also considered when an individual is exposed to PAHs, especially in environments with strong sunlight.

Anthraquinone biocolourant dermocybin is metabolized whereas dermorubin is not in in vitro liver fractions and recombinant metabolic enzymes.

Fungal anthraquinones dermocybin and dermorubin are attractive alternatives for synthetic dyes but their metabolism is largely unknown. We conducted a qualitative in vitro study to identify their metabolism using human liver microsomes and cytosol, as well as recombinant human cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes. Additionally, liver microsomal and cytosolic fractions from rat, mouse and pig were used. Following incubations of the biocolourants with the enzymes in the presence of nicotinamide adenine dinucleotide phosphate, UDP-glucuronic acid, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) or S-adenosyl methionine (SAM) to enable CYP oxidation, glucuronidation, sulfonation or methylation, we observed several oxidation and conjugation metabolites for dermocybin but none for dermorubin. Human CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A7 catalysed dermocybin oxidation. The formation of dermocybin glucuronides was catalysed by human UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10 and 2B15. Human SULT1B1, 1C2 and 2A1 sulfonated dermocybin. Dermocybin oxidation was faster than conjugation in human liver microsomes. Species differences were seen in dermocybin glucuronidation between human, rat, mouse and pig. In conclusion, many CYP and conjugation enzymes metabolized dermocybin, whereas dermorubin was not metabolized in human liver fractions in vitro. The results indicate that dermocybin would be metabolized in humans in vivo.

Preparation of novel Fe-containing zeolite-A for KN-R decolorization by Fenton-like reaction.

Herein, novel catalysts of Fe-containing zeolite-A (Fe/zeolite-A) were synthesized by exchanging iron ions into zeolite-A framework, and short-chain organic acids (SCOAs) were employed as chelating agents. Reactive Brilliant Blue KN-R (KN-R) was used as a model pollutant to evaluate the performance of these catalysts based on the heterogeneous Fenton reaction. The results showed that Fe-OA/3A, which applied zeolite-3A as the supporter and oxalic as the chelating agent, presented the most prominent KN-R decolorization efficiency. Under the initial pH of 2.5, 0.4 mM KN-R could be totally decolorized within 20 min. However, the mineralization efficiency of KN-R was only 58.2%. Therefore, anthraquinone dyes were introduced to modify zeolite-3A. As a result, the mineralization efficiency of KN-R was elevated to 92.7% when using Alizarin Violet (AV) as the modifier. Moreover, the modified catalysts exhibited excellent stability, the KN-R decolorization efficiency could be maintained above 95.0% within 20 min after operating for nine cycles. The mechanism revealed that the Fe(II)/Fe(III) cycle was accelerated by AV-modified catalyst thus prompting the KN-R decolorization in Fenton-like system. These findings provide new insights for preparing catalysts with excellent activity and stability for dye wastewater treatment.