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.

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.

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.

Synergistic promotion of angiogenesis after intracerebral hemorrhage by ginsenoside Rh2 and chrysophanol in rats.

BACKGROUND: Intracerebral hemorrhage (ICH) is a debilitating condition characterized by the rupture of cerebral blood vessels, resulting in profound neurological deficits. A significant challenge in the treatment of ICH lies in the brain's limited capacity to regenerate damaged blood vessels. This study explores the potential synergistic effects of Ginsenoside Rh2 and Chrysophanol in promoting angiogenesis following ICH in a rat model. METHODS: Network pharmacology was employed to predict the potential targets and pathways of Ginsenoside Rh2 and Chrysophanol for ICH treatment. Molecular docking was utilized to assess the binding affinity between these compounds and their respective targets. Experimental ICH was induced in male Sprague-Dawley rats through stereotactic injection of type VII collagenase into the right caudate putamen (CPu). The study encompassed various methodologies, including administration protocols, assessments of neurological function, magnetic resonance imaging, histological examination, observation of brain tissue ultrastructure, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, Western blot analysis, and statistical analyses. RESULTS: Network pharmacology analysis indicated that Ginsenoside Rh2 and Chrysophanol may exert their therapeutic effects in ICH by promoting angiogenesis. Results from animal experiments revealed that rats treated with Ginsenoside Rh2 and Chrysophanol exhibited significantly improved neurological function, reduced hematoma volume, and diminished pathological injury compared to the Model group. Immunofluorescence analysis demonstrated enhanced expression of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31, signifying augmented angiogenesis in the peri-hematomal region following combination therapy. Importantly, the addition of a VEGFR2 inhibitor reversed the increased expression of VEGFR2 and CD31. Furthermore, Western blot analysis revealed upregulated expression of angiogenesis-related factors, including VEGFR2, SRC, AKT1, MAPK1, and MAPK14, in the combination therapy group, but this effect was abrogated upon VEGFR2 inhibitor administration. CONCLUSION: The synergistic effect of Ginsenoside Rh2 and Chrysophanol demonstrated a notable protective impact on ICH injury in rats, specifically attributed to their facilitation of angiogenesis. Consequently, this research offers a foundation for the utilization of Ginsenosides Rh2 and Chrysophanol in medical settings and offers direction for the advancement of novel pharmaceuticals for the clinical management of ICH.

Metabolic Blockade-Based Genome Mining of Sea Anemone-Associated Streptomyces sp. S1502 Identifies Atypical Angucyclines WS-5995 A-E: Isolation, Identification, Biosynthetic Investigation, and Bioactivities.

Marine symbiotic and epiphyte microorganisms are sources of bioactive or structurally novel natural products. Metabolic blockade-based genome mining has been proven to be an effective strategy to accelerate the discovery of natural products from both terrestrial and marine microorganisms. Here, the metabolic blockade-based genome mining strategy was applied to the discovery of other metabolites in a sea anemone-associated Streptomyces sp. S1502. We constructed a mutant Streptomyces sp. S1502/Δstp1 that switched to producing the atypical angucyclines WS-5995 A-E, among which WS-5995 E is a new compound. A biosynthetic gene cluster (wsm) of the angucyclines was identified through gene knock-out and heterologous expression studies. The biosynthetic pathways of WS-5995 A-E were proposed, the roles of some tailoring and regulatory genes were investigated, and the biological activities of WS-5995 A-E were evaluated. WS-5995 A has significant anti-Eimeria tenell activity with an IC50 value of 2.21 µM. The production of antibacterial streptopyrroles and anticoccidial WS-5995 A-E may play a protective role in the mutual relationship between Streptomyces sp. S1502 and its host.

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.

Progress in phosphorylation of natural products.

Natural medicines are a valuable resource for the development of new drugs. However, factors such as low solubility and poor bioavailability of certain constituents have hindered their efficacy and potential as pharmaceuticals. Structural modification of natural products has emerged as an important research area for drug development. Phosphorylation groups, as crucial endogenous active groups, have been extensively utilized for structural modification and development of new drugs based on natural molecules. Incorporating phosphate groups into natural molecules not only enhances their stability, bioavailability, and pharmacological properties, but also improves their biological activity by altering their charge, hydrogen bonding, and spatial structure. This review summarizes the phosphorylation mechanism, modification approaches, and biological activity enhancement of natural medicines. Notably, compounds such as polysaccharides, flavonoids, terpenoids, anthraquinones, and coumarins exhibit increased antioxidation, anticancer, antiviral, immune regulatory, Antiaging, enzyme inhibition, bacteriostasis, liver protection, and lipid-lowering effects following phosphorylation modification.

[Effect and mechanism of free total rhubarb anthraquinones on pyroptosis of J774A.1 macrophages].

In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.

Plants-occurring Anthraquinones as Photosensitive Compounds for Photodynamic Method: A Critical Overview.

The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and palliative method named photodynamic therapy (PDT). Green approach to PDT is associated with photosensitizers (PS) from plants or other natural sources and excitation light in visible spectrum. The investigations of plants are of high research interests due to their unique health supportive properties as herbs and the high percentage availability to obtain compounds with medical value. Up-to-date many naturally occurring compounds with therapeutic properties are known and are still under investigations. Some natural quinones have already been evaluated and clinically approved as anti-tumor agents. Recent scientific interests are beyond their common medical applications but also in directions to their photo-properties as natural PSs. The study presents a systematic searches on the latest knowledge on AQ derivatives that are isolated from the higher plants as photosensitizers for PDT applications. The natural quinones have been recognized with functions of natural dyes since the ancient times. Lately, AQs have been explored due to their biological activity including the photosensitive properties useful for PDT especially towards medical problems with no other alternatives. The existing literature' overview suggests that natural AQs possess characteristics of valuable PSs for PDT. This method is based on an application of a photoactive compound and light arrangement in oxygen media, such that the harmful general cytotoxicity could be avoided. Moreover, the common anticancer and antimicrobial drug resistance has been evaluated with very low occurrence after PDT. Natural AQs have been focused the scientific efforts to further developments because of the high range of natural sources, desirable biocompatibility, low toxicity, minimal side effects and low accident of drug resistance, together with their good photosensitivity and therapeutic capacity. Among the known AQs, only hypericin has been studied in anticancer clinical PDT. Currently, the natural PSs are under intensive research for the future PDT applications for diseases without alternative effective treatments.

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A systematic review.

BACKGROUND: In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment. METHODS: The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023. RESULTS: Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion. CONCLUSION: By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.

Aloe-emodin alleviates cerebral ischemia-reperfusion injury by regulating microglial polarization and pyroptosis through inhibition of NLRP3 inflammasome activation.

BACKGROUND: Microglial activation plays a crucial role in injury and repair after cerebral ischemia, and microglial pyroptosis exacerbates ischemic injury. NOD-like receptor protein 3 (NLRP3) inflammasome activation has an important role in microglial polarization and pyroptosis. Aloe-emodin (AE) is a natural anthraquinone compound originated from rhubarb and aloe. It exerts antioxidative and anti-apoptotic effects during cerebral ischemia/reperfusion (I/R) injury. However, whether AE affects microglial polarization, pyroptosis, and NLRP3 inflammasome activation remains unknown. PURPOSE: This study aimed to explore the effects of AE on microglial polarization, pyroptosis, and NLRP3 inflammasome activation in the cerebral infarction area after I/R. METHODS: The transient middle cerebral artery occlusion (tMCAO) and oxygen-glucose deprivation/re-oxygenation (OGD/R) methods were used to create cerebral I/R models in vivo and in vitro, respectively. Neurological scores and triphenyl tetrazolium chloride and Nissl staining were used to assess the neuroprotective effects of AE. Immunofluorescence staining, quantitative polymerase chain reaction and western blot were applied to detect NLRP3 inflammasome activation and microglial polarization and pyroptosis levels after tMCAO or OGD/R. Cell viability and levels of interleukin (IL)-18 and IL-1ß were measured. Finally, MCC950 (an NLRP3-specific inhibitor) was used to evaluate whether AE affected microglial polarization and pyroptosis by regulating the activation of the NLRP3 inflammasome. RESULTS: AE improved neurological function scores and reduced the infarct area, brain edema rate, and Nissl-positive cell rate following I/R injury. It also showed a protective effect on BV-2 cells after OGD/R. AE inhibited microglial pyroptosis and induced M1 to M2 phenotype transformation and suppressed microglial NLRP3 inflammasome activation after tMCAO or OGD/R. The combined administration of AE and MCC950 had a synergistic effect on the inhibition of tMCAO- or OGD/R-induced NLRP3 inflammasome activation, which subsequently suppressed microglial pyroptosis and induced microglial phenotype transformation. CONCLUSION: AE exerts neuroprotective effects by regulating microglial polarization and pyroptosis through the inhibition of NLRP3 inflammasome activation after tMCAO or OGD/R. These findings provide new evidence of the molecular mechanisms underlying the neuroprotective effects of AE and may support the exploration of novel therapeutic strategies for cerebral ischemia.

Enhancement of bio-promoters on hexavalent chromium inhibited sulfur-driven denitrification: repairing damage, accelerating electron transfer, and reshaping microbial collaboration.

Proposing recovery strategies to recover heavy-metal-inhibited sulfur-driven denitrification, as well as disclosing recovery mechanisms, can provide technical support for the stable operation of bio-systems. This study proposed an effective bio-promoter (mediator-promoter composed of L-cysteine, biotin, cytokinin, and anthraquinone-2,6-disulfonate) to recover Cr(VI) inhibited sulfur-driven denitrification, which effectively reduced the recovery time of NO3--N reduction (18-21 cycles) and NO2--N reduction (27-42 cycles) compared with self-recovery. The mediator-promoter repaired microbial damage by promoting intracellular chromium efflux. Moreover, the mediator-promoter reduced the accumulated reactive oxygen species by stimulating the secretion of antioxidant enzymes, reaching equilibrium in the oxidative-antioxidant system. To improve electron transmission, the mediator-promoter restored S2O32- oxidation to provide adequate electron donors and increased electron transfer rate by increasing cytochrome c levels. Mediator-promoter boosted the abundance of Thiobacillus (sulfur-oxidizing bacterium) and Simplicispira (denitrifying bacterium), which were positively correlated, facilitating the rapid denitrification recovery and the long-term stable operation of recovered systems.

Rhein kills Actinobacillus pleuropneumoniae, reduces biofilm formation, and effectively treats bacterial lung infections in mice.

Background. Actinobacillus pleuropneumoniae, a member of the Pasteurellaceae family, is known for its highly infectious nature and is the primary causative agent of infectious pleuropneumonia in pigs. This disease poses a considerable threat to the global pig industry and leads to substantial economic losses due to reduced productivity, increased mortality rates, and the need for extensive veterinary care and treatment. Due to the emergence of multi-drug-resistant strains, Chinese herbal medicine is considered one of the best alternatives to antibiotics due to its unique mechanism of action and other properties. As a type of Chinese herbal medicine, Rhein has the advantages of a wide antibacterial spectrum and is less likely to develop drug resistance, which can perfectly solve the limitations of current antibacterial treatments.Methods. The killing effect of Rhein on A. pleuropneumoniae was detected by fluorescence quantification of differential expression changes of key genes, and scanning electron microscopy was used to observe the changes in A. pleuropneumoniae status after Rhein treatment. Establishing a mouse model to observe the treatment of Rhein after A. pleuropneumoniae infection.Results. Here, in this study, we found that Rhein had a good killing effect on A. pleuropneumoniae and that the MIC was 25 µg ml-1. After 3 h of action, Rhein (4×MIC) completely kills A. pleuropneumoniae and Rhein has good stability. In addition, the treatment with Rhein (1×MIC) significantly reduced the formation of bacterial biofilms. Therapeutic evaluation in a murine model showed that Rhein protects mice from A. pleuropneumoniae and relieves lung inflammation. Quantitative RT-PCR (Quantitative reverse transcription polymerase chain reaction is a molecular biology technique that combines both reverse transcription and polymerase chain reaction methods to quantitatively detect the amount of a specific RNA molecule) results showed that Rhein treatment significantly downregulated the expression of the IL-18 (Interleukin refers to a class of cytokines produced by white blood cells), TNF-α, p65 and p38 genes. Along with the downregulation of genes such as IL-18, it means that Rhein has an inhibitory effect on the expression of these genes, thereby reducing the activation of inflammatory cells and the production of inflammatory mediators. This helps reduce inflammation and protects tissue from further damage.Conclusions. This study reports the activity of Rhein against A. pleuropneumoniae and its mechanism, and reveals the ability of Rhein to treat A. pleuropneumoniae infection in mice, laying the foundation for the development of new drugs for bacterial infections.

Repurposing diacerein to suppress colorectal cancer growth by inhibiting the DCLK1/STAT3 signaling pathway.

Double cortin-like kinase 1 (DCLK1) exhibits high expression levels across various cancers, notably in human colorectal cancer (CRC). Diacerein, a clinically approved interleukin (IL)-1ß inhibitor for osteoarthritis treatment, was evaluated for its impact on CRC proliferation and migration, alongside its underlying mechanisms, through both in vitro and in vivo analyses. The study employed MTT assay, colony formation, wound healing, transwell assays, flow cytometry, and Hoechst 33342 staining to assess cell proliferation, migration, and apoptosis. Additionally, proteome microarray assay and western blotting analyses were conducted to elucidate diacerein's specific mechanism of action. Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo. Through high-throughput proteomics microarray and molecular docking studies, we identified that diacerein directly interacts with DCLK1. Mechanistically, the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed. Furthermore, diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets, including MCL-1, VEGF, and survivin, thereby inhibiting CRC progression in a mouse model, thereby inhibiting CRC progression in a mouse model.

Chemical constituents of Rubia tibetica Hook. f. from Tibetan medicine and cytotoxic activity evaluation.

Two unprecedented quinone compounds Rubiaxylm A (1) and Rubiaxylm B (2), along with fifteen known anthraquinones (3-17) were isolated and characterized from the roots of Rubia tibetica in Tibetan medicine. Their structures were identified through comprehensive analyses of 1D/2D NMR as well as HR-ESIMS data. Furthermore, all separated compounds were evaluated for their cytotoxic activity on A549, Caco-2, MDA-MB-231 and Skov-3 cell lines. In particular, compound 2 effectively inhibited MDA-MB-231 cells with an IC50 value of 8.15 ± 0.20 µM. Subsequently, the anti-tumor mechanism of 2 was investigated by flow cytometry, JC-1 staining, cell scratching and cell colony. These results indicated that compound 2 could inhibit the proliferation of MDA-MB-231 cells by arresting cells in the G1 phase.

Exploring the potential of Aspergillus wentii: secondary metabolites and biological properties.

Fungi are of considerable importance due to their capacity to biosynthesize various secondary metabolites with bioactive properties that draw high attention in new drug discovery with beneficial uses for improving human well-being and life quality. Aspergillus genus members are widespread and cosmopolitan species with varying economic significance in the fields of industry, medicine, and agriculture. Its species are renowned for their biosynthesis of secondary metabolites, characterized by both potent biological activity and structural novelty, making them a substantial reservoir for the development of new pharmaceuticals. The current work aimed at focusing on one species of this genus, Aspergillus wentii Wehmer, including its reported secondary metabolites in the period from 1951 to November 2023. A total of 97 compounds, including nitro-compounds, terpenoids, anthraquinones, xanthones, benzamides, and glucans. A summary of their bioactivities, as well as their biosynthesis was highlighted. Additionally, the reported applications of this fungus and its enzymes have been discussed. This review offers a useful reference that can direct future research into this fungus and its active metabolites, as well as their possible pharmacological and biotechnological applications.

Exploring the interaction of biologically active compounds with DNA through the application of the SwitchSense technique, UV-Vis spectroscopy, and computational methods.

DNA is a key target for anticancer and antimicrobial drugs. Assessing the bioactivity of compounds involves in silico and instrumental studies to determine their affinity for biomolecules like DNA. This study explores the potential of the switchSense technique in rapidly evaluating compound bioactivity towards DNA. By combining switchSense with computational methods and UV-Vis spectrophotometry, various bioactive compounds' interactions with DNA were analyzed. The objects of the study were: netropsin (as a model compound that binds in the helical groove), as well as derivatives of pyrazine (PTCA), sulfonamide (NbutylS), and anthraquinone (AQ-NetOH). Though no direct correlation was found between switchSense kinetics and binding modes, this research suggests the technique's broader utility in assessing new compounds' interactions with DNA. used as analytes whose interactions with DNA have not been yet fully described in the literature.

A multi-mode Rhein-based nano-platform synergizing ferrotherapy/chemotherapy-induced immunotherapy for enhanced tumor therapy.

Ferroptosis has emerged as a promising strategy for treating triple-negative breast cancer (TNBC) due to bypassing apoptosis and triggering immunogenic cell death (ICD) of tumor cells. However, the antitumor efficacy has been limited by the insufficient intracellular ferrous iron concentration required for ferroptosis and inadequate antitumor immune response. To address these limitations, we designed a multi-mode nano-platform (MP-FA@R-F NPs), which exhibited a synergistic effect of ferroptosis, apoptosis and induced immune response for enhanced antitumor therapy. MP-FA@R-F NPs target folate receptors, which are over-expressed on the tumor cell's surface to promote intracellular uptake. The cargoes, including Rhein and Fe3O4, would be released in intracellular acid, accelerating by NIR laser irradiation. The released Rhein induced apoptosis of tumor cells mediated by the caspase 3 signal pathway, while the released Fe3O4 triggered ferroptosis through the Fenton reaction and endowed the nanoplatform with magnetic resonance imaging (MRI) capabilities. In addition, ferroptosis-dying tumor cells could release damage-associated molecular patterns (DAMPs) to promote T cell activation and infiltration for immune response and induce immunogenic cell death (ICD) for tumor immunotherapy. Together, MP-FA@R-F NPs represent a potential synergistic ferro-/chemo-/immuno-therapy strategy with MRI guidance for enhanced antitumor therapy. STATEMENT OF SIGNIFICANCE: The massive strategies of cancer therapy based on ferroptosis have been emerging in recent years, which provided new insights into designing materials for cancer therapy. However, the antitumor efficacy of ferroptosis is still unsatisfactory, mainly due to insufficient intracellular pro-ferroptotic stimuli. In the current study, we designed a multi-mode nano-platform (MP-FA@R-F NPs), which represented a potential synergistic ferro-/chemo-/immuno-therapy strategy with MRI guidance for enhanced antitumor therapy.

Elucidation of inhibitory effects of bioactive anthraquinones towards formation of DNA advanced glycation end products (DNA-AGEs).

DNA is essential in biological processes as it directs transcription and translation assisting in RNA and protein synthesis. Extended periods of elevated blood glucose levels cause non-enzymatic DNA glycation, which results in the formation of DNA-AGEs and the production of free radicals, causing structural perturbation of DNA. In this work, we have investigated the glycation of calf thymus (ct-DNA) DNA and examined its inhibition by two anthraquinone derivatives, purpurin and aloin. Ribose sugar served as the glycating agent inducing non-enzymatic glycation of DNA and subsequent DNA-AGEs formation. UV-vis and fluorescence spectroscopic methods were utilized to characterize DNA-AGE formation in vitro. Circular dichroism (CD) spectroscopy was used to observe the structural disruption of DNA caused by glycation. The changes in AGEs fluorescence intensity and melting temperature (Tm) were measured to assess the inhibition of glycation process by aloin and purpurin. These derivatives demonstrated inhibitory effects via binding to glycating sites of ct-DNA or by scavenging free radicals generated during glycation. The current study elucidates the inhibitory actions of aloin and purpurin on DNA glycation, suggesting their possible applications in mitigating the adverse consequences linked to increased ribose concentrations.

Synthesis of a New Series of Anthraquinone-Linked Cyclopentanone Derivatives: Investigating the Antioxidant, Antibacterial, Cytotoxic and Tyrosinase Inhibitory Activities of the Mushroom Tyrosinase Enzyme Using Molecular Docking.

Purpose: New bioactive anthraquinone derivatives are investigated for antibacterial, tyrosinase inhibitory, antioxidant cytotoxic activity, and molecular docking. Methods: The compounds were produced using the grindstone method, yielding 69 to 89%. These compounds were analyzed using IR, 1H, and 13C NMR and elemental and mass spectral methods. Additionally, the antibacterial, antioxidant, and tyrosinase inhibitory activities of all the synthesised compounds were evaluated. Results: Compound 2 showed remarkable tyrosinase inhibition activity, with an (IC50: 13.45 µg/mL), compared to kojic acid (IC50: 19.40 µg/mL). It also exhibited moderate antioxidant and antibacterial activities with respect to the references BHT and ampicillin, respectively. Kinetic analysis revealed that the tyrosinase inhibitory activity of compound 2 was non-competitive and competitive, whereas that of compound 1 was low. All compounds (1-8) were significantly less active than doxorubicin (LC50: 0.74±0.01µg/mL). However, compound 2 affinity for the 2Y9X protein was lower than kojic acid, with a lower docking score (-8.6 kcal/mol compared to (-4.7 kcal/mol), making it more effective. Conclusion: All synthesized compounds displayed remarkable antibacterial, tyrosinase inhibitory, antioxidant, and cytotoxic activities, with compound 2 showing exceptional potency as a multitarget agent. Anthraquinone substituent groups may offer the potential for the development of treatments. The derivatives were synthesized using the grindstone method, and their antibacterial, antioxidant, tyrosinase inhibitory, and cytotoxic activities were inspected. Molecular docking and molecular dynamics simulations were performed using compound 2 and kojic acid to validate the results and confirm the stability of the compounds.