Search Results (242)

This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling axis. Bovine type II collagen-induced arthritis (CIA) mouse models and lipopolysaccharide (LPS)-stimulated EA.hy926 endothelial cells were utilized in this study. The effects of EMO on joint pathological alterations, the expression of NF-κB/HIF-1α/VEGF axis proteins, inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)), and angiogenic capacity were assessed using histopathological analysis, Western blotting, immunohistochemistry (IHC), immunofluorescence, and tube formation assays. Furthermore, small interfering RNA (siRNA) interference targeting key molecules was employed to validate the molecular mechanisms underlying the therapeutic effects of EMO. In the CIA model group, the ankle joints of mice exhibited pronounced inflammatory infiltration, synovial hyperplasia, and bone destruction. Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-κB pathway proteins, HIF-1α, and VEGF in joint tissues (p < 0.001). In vitro experiments revealed that EMO treatment significantly reduced the LPS-induced secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) (p < 0.001), and decreased both the number and total length of tubular structures formed by endothelial cells compared to the control (p < 0.001). Notably, siRNA-mediated knockdown of p65 resulted in decreased intracellular protein levels of HIF-1α and VEGF, accompanied by a significant reduction in tube formation (p < 0.001). This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-κB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1α/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA. Full article

Estrogen deficiency is an established risk factor for menopausal brain dysfunctions in women. Urgent exploration of drugs is needed to improve estrogen deficiency-related brain dysfunctions without the side effects of estrogen supplements. Three-month-old rats had bilateral ovariectomy (OVX) performed and were treated with emodin (EMO, 80 mg/kg/day) and 17 β-estradiol (EST, 0.5 mg/kg/day). Brain functions were evaluated by cognition and emotion-related behavioral tests. Levels of glucagon-like peptide-1 (GLP-1) and estrogen in blood, mRNA levels of estrogen receptor (ER) α, ERβ, GLP-1 receptor (GLP-1R), proprotein convertase subtilisin/kexin type 1 (PCSK1) and proglucagon (proGCG) in intestinal segments, and brain ERα and GLP-1R levels were evaluated. Contractions of isolated intestinal segments were recorded. Additionally, an ERβ antagonist, PHTPP (200 μg/kg/day), was used to clarify the role of ERβ. EST and EMO significantly ameliorated cognition deficit and depressive behaviors in OVX rats, and reduced neuronal loss and synaptic abnormalities in the hippocampus and prefrontal cortex. The blood GLP-1 levels of sham operation rats (sham, 3.09 pg/mL), EMO-treated (2.57 pg/mL) and EST-treated OVX rats (2.64 pg/mL), were higher than that of OVX rats (1.03 pg/mL). EMO had no effect on the blood estrogen level. Furthermore, EMO up-regulated mRNA levels of ERβ in ileum, colon, and cerebral GLP-1R level, while EST increased mRNA levels of ERβ in colon and cerebral ERα level. In vitro intestinal segment spontaneous contraction tests revealed that EMO reduced contraction amplitudes in isolated intestinal segments from OVX rats, with the ileum and proximal colon showing greater sensitivity to EMO. The ileum and colon segments from OVX rats were less sensitive to EST as compared to those of normal rats. Upon PHTPP intervention, the up-regulated intestinal mRNA levels of ERβ, PCSK1, proGCG, blood GLP-1 level by EMO, and the beneficial effects of EMO in abnormal behaviors of OVX rats were significantly inhibited. Overall, it was found that EMO up-regulated blood GLP-1 level via intestinal Erβ-dependent mechanism and increased brain GLP-1R level, which may be involved in the neuroprotection of EMO in OVX animals. Full article

Aloe-emodin is an anthraquinone with a wide range of medicinal applications, including anti-angiogenic, anticancer, antimicrobial, antiviral, anti-inflammatory, and antioxidant activities. In this review, the functionalization of aloe-emodin using various synthetic methods, including alkylation, condensation, esterification, the Finkelstein reaction, and the Kabachnik–Fields reaction was reported. The biological activity of the synthesized aloe-emodin derivatives is discussed, with a focus on their potential future applications as anticancer agents, enzyme inhibitors, anti-inflammatory agents, and antimicrobial agents. This review also discusses the structure–activity relationship (SAR) and the mechanism of action (e.g., molecular docking studies, cell membrane-disrupting capacity, and apoptosis studies). This review highlights the many contributions made towards the design and development of novel, biologically active aloe-emodin derivatives. Full article

Natural anthraquinones possess a wide range of biological activities, including antibacterial, antiviral, antitumor, and antioxidant effects. However, studies on their ability to inhibit amyloid protein aggregation remain relatively limited. In this study, we used insulin as a model protein to investigate the anti-amyloidogenic potential of several natural anthraquinones. Specifically, the inhibitory mechanisms of five anthraquinones (emodin, anthraflavin, aloe-emodin, alizarin, and purpurin) on insulin amyloid fibrillation were explored in both dilute and crowded environments (PEG 2000 and PEG 4000). Multidisciplinary analytical results demonstrated that all five anthraquinones could effectively inhibit insulin amyloid fibrillation in both dilute and crowded environments. Simultaneously, crowded agents themselves also exhibited inhibitory effects on insulin amyloid aggregation. However, the inhibitory efficacy of anthraquinones was weaker in crowded environments than in dilute solutions, indicating that although crowded agents themselves suppressed insulin aggregation, they may interfere with the regulatory roles of anthraquinones on insulin aggregation behavior. Interestingly, purpurin showed stronger inhibitory activity in crowded environments compared to dilute solutions. Furthermore, fluorescence spectral analysis suggested that the quenching mechanism of insulin by all these anthraquinones was identified as static quenching mode. Molecular simulation studies revealed that anthraquinones could bind to the aggregation-prone regions of insulin via hydrogen bonding and hydrophobic interactions, thereby inhibiting insulin amyloid aggregation. Notably, the inhibitory capacity of these compounds was correlated with their structural features and the binding affinities to insulin. Collectively, this study explored the anti-amyloid activity of anthraquinones, which held significant research value for the development of potential therapeutic agents for amyloid-associated proteinopathies. Full article

Emodin, a trihydroxy-methyl anthraquinone abundant in rhubarb, Polygonum species, and other medicinal plants, exemplifies the therapeutic potential and translational complexity of the broader anthraquinone scaffold. Anthraquinone derivatives have demonstrated antiproliferative, anti-inflammatory, metabolic, cardiovascular, antifibrotic, and immunomodulatory effects, consistently reported across diverse preclinical models, targeting pathways such as NF-κB, PI3K/AKT, MAPKs, AMPK, PPARs, NLRP3, and ferroptosis-related axes. Despite strong preclinical efficacy, clinical development has been limited by unfavorable absorption, distribution, metabolism, and excretion (ADME) characteristics, including poor aqueous solubility, extensive first-pass glucuronidation, and active efflux via intestinal and hepatic transporters. These features result in low and variable systemic exposure, while high local concentrations, particularly in the gastrointestinal tract, contribute to context-dependent toxicity signals that complicate risk assessment. The present review integrates pharmacological, toxicological, and formulation-focused evidence to provide a unified assessment of emodin and the anthraquinone scaffold. Particular emphasis is placed on bidirectional, dose- and context-dependent effects on the liver and kidney; the modulation of cytochrome P450 enzymes, UGTs, and transporters; and emerging preclinical formulation strategies that aim to decouple intrinsic bioactivity from pharmacokinetic limitations. Full article

Background/Objectives: There is high demand for Anshenbunao syrup (ABS) in Chinese medicine owing to its steady therapeutic efficacy for insomnia and neurasthenia. However, it contains a substantial proportion of Polygoni Multiflori Radix Praeparata (PMRP), which is associated with reported cases of drug-induced liver injury (DILI). Here, we aim to establish an integrated approach combining PK screening with a dual-model toxicity verification system to systematically identify liver injury components (from high to low concentrations and from direct to idiosyncratic hepatotoxicity) to accurately uncover diverse potential hepatotoxicity markers. Methods: A sensitive UPLC-MS/MS method was used to accurately quantify the components in plasma at the ng/mL level and conduct a pharmacokinetic analysis. Rat models were used to evaluate exposure levels of the eight active constituents and three major metabolites after a single oral gavage dose of 10 mL/kg ABS and identify the quality markers. The early-stage and high-throughput assessment of direct and idiosyncratic hepatotoxicity was conducted in vitro utilizing HepG2 cells. After the administration of the quality markers (0.01–80 μM), CCK-8 was used to detect cell viability on both normal and susceptible cells, and the latter was induced by lipopolysaccharide. Results: As a result, seven quality markers were screened based on their contents and exposure levels in rat plasma by UPLC–MS/MS, including emodin (EM), liquiritin (LI), 2,3,5,4′–Tetrahydroxystilbene–2–O–β–D–glucoside (TSG), icariin, emodin–8–O–β–D–glucoside, baohuoside I (BA), and 18β–glycyrrhetinic acid (GTA). Moreover, the half maximal inhibitory concentration values of both normal cells and the lipopolysaccharide-induced immune stress liver injury cells were fitted within the concentration range of 0.01–80 μM, based on which, EM, BA, and GTA were identified as the principal hepatotoxic constituents in ABS at elevated concentrations. This study is the first to demonstrate that TSG, EM, LI, and GTA exhibit synergistic cytotoxicity in LPS-sensitized hepatocytes at clinically relevant concentrations, whereas EM was also a direct hepatotoxic component. Given that TSG is one of the major ingredients in ABS, the underappreciated idiosyncratic hepatotoxicity could elevate the risk of adverse clinical outcomes. Conclusions: In conclusion, this study effectively identifies hepatotoxic constituents in ABS and evaluates their hazards under immune stress and toxicity profiles in clinical concentrations, which also provides a robust foundation for the awareness of PMRP-induced DILI due to ABS. Full article

Fluoride-induced osteoarthritis (F-OA) is a debilitating manifestation of endemic fluorosis, with limited preventive or therapeutic strategies. Rosa roxburghii juice (RRJ), a traditional medicinal/edible product, has shown protective effects against skeletal fluorosis, yet its active constituents and molecular mechanisms are not fully understood. In this study, an integrated strategy combining bioinformatics analysis, network pharmacology, molecular docking and dynamics simulations, limited proteolysis–mass spectrometry (LiP–MS), and in vitro experiments was employed to systematically elucidate the protective mechanisms of RRJ against F-OA. Forty-four core F-OA-associated genes were identified, with TP53 and the p53 signaling pathway emerging as central regulatory hubs. Quercetin, Epicatechin, Emodin, and Ellagic acid were screened as key bioactive components of RRJ and demonstrated strong binding affinity toward core targets, including TP53. Cellular experiments showed that these compounds significantly attenuated sodium fluoride-induced cellular injury. LiP–MS analysis further revealed widespread protein conformational remodeling following treatment, with TP53 exhibiting pronounced structural sensitivity. Mechanistically, these active compounds mitigated fluoride-induced pathological changes by suppressing p53 mRNA expression and restoring proteasome-mediated p53 degradation. This study provides systematic pharmacological evidence supporting Rosa roxburghii fruit as a promising functional food for the prevention and management of skeletal fluorosis and F-OA. Full article

Objectives: Polygonum cuspidatum Sieb. et Zucc (PC) has traditionally been used for inflammatory and circulatory disorders; however, the systems-level mechanisms of its effect on cardiometabolic disease processes, including insulin resistance and vascular injury, remain incompletely understood. This study aimed to identify biological pathways potentially modulated by PC through the integration of network pharmacology with patient-derived transcriptomic data. Methods: Four representative compounds—resveratrol, polydatin, emodin, and physcion—were selected based on previously reported chemical fingerprints that characterize PC. Predicted targets were obtained from public compound–target databases and used to construct a compound–target network. Functional enrichment was performed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Genetic Association Database (GAD) disease associations. To evaluate clinical relevance, predicted targets were compared with differentially expressed genes (DEGs) from insulin-resistant adipose tissue (GSE20950) and atherosclerotic lesions (GSE43292). Results: A total of 329 predicted target genes were identified, with resveratrol emerging as the dominant topological hub (214 targets). Network and enrichment analyses highlighted MAPK14, MAPT, VEGFA, IL1B, NLRP3, and HMOX1 as key targets involved in inflammatory, oxidative, and vascular injury pathways that overlapped with transcriptomic signatures. KEGG analysis demonstrated significant enrichment in AGE–RAGE signaling, TNF-mediated inflammation, and lipid–atherosclerosis pathways, while GAD mapping indicated associations with type 2 diabetes and atherosclerosis. Integration of transcriptomic datasets further supported a convergence on coordinated inflammatory and oxidative processes driving vascular remodeling. Conclusions: These findings suggest that the major constituents of PC may modulate interconnected cardiometabolic processes linking insulin resistance and vascular injury implicated in atherosclerotic cardiovascular disease. By integrating network pharmacology with patient-derived transcriptomic evidence, this study provides a systems-level framework for interpreting the potential biological roles of PC in insulin resistance and vascular injury. Full article

So-called ‘war rugs’ started being produced in Afghanistan after the Soviet invasion in 1979. These textiles have sparked debate as symbols of resilience and political commentary but also as controversial commodification of human suffering. However, their manufacture and materiality have not been studied so far. In the framework of the British Museum exhibition “War rugs: Afghanistan’s knotted history”, a scientific investigation was conducted on nine rugs from the collection. Approximately 65 samples were analysed by optical microscopy (OM), scanning electron microscopy coupled to energy dispersive X-ray spectroscopy (SEM-EDX) and high-pressure liquid chromatography coupled to diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS) to study the fibres, mordants and dyes used in the production of the rugs. Scanning X-ray fluorescence (MA-XRF) and multiband imaging (MBI) were also used directly on the rugs to map the distribution of specific mordants and dyes, respectively. The results revealed the intentional use of white or dark wool as the substrate for dyeing, to obtain specific colour shades. A wide range of synthetic dyes was detected, including Acid Orange 7, Acid Red 88, Basic Green 4, Acid Blue 92, Acid Black 1 and Direct Black 38 in the earlier rugs, whereas Direct Yellow 1, Direct Brown 1, Direct Yellow 12, Acid Green 25, Acid Blue 113 and Direct Blue 15 were identified in the later rugs. Some synthetic dyes remained unidentified. Additionally, natural dyes were used in three rugs. An emodin-based colourant, possibly obtained from dock or sorrel (Rumex spp.), was detected in two light brown areas. A berberine-based colourant consistent with barberry (Berberis spp.) was detected in a yellow area. These results represent the first scientific study of these objects and enable preliminary insights into the details of this complex craft that has evolved from centuries of carpet making in this area. Full article

This study aimed to develop natural, safe, and effective antimicrobial packaging materials for extending the shelf life of chilled pork during refrigeration. Emodin-chitosan (Em-Cs) composite films with varied concentrations were developed by combining the casting method with photodynamic inactivation technology, utilizing chitosan as the matrix and emodin as the functional photosensitizer for active packaging. The optical, mechanical, and barrier properties of the composite films were examined. The inhibitory effects of the samples on Escherichia coli, Salmonella Derby, Staphylococcus aureus, and Pseudomonas fragi under 450 nm blue light irradiation were evaluated. The results demonstrated that the Em-Cs composite film exhibited excellent transparency, mechanical strength, and water barrier properties, with good compatibility between emodin and chitosan. Under light irradiation, the composite film generates reactive oxygen species (ROS), whose bactericidal efficacy depends on the concentration of emodin and the duration of light exposure. When applied to chilled pork packaging, this composite film inhibited bacterial growth within the meat for 10 days, effectively retarding pH increase, lipid oxidation, and volatile basic nitrogen accumulation. The present study proposes a novel methodology for the application of photodynamic technology in the context of food preservation, and it presents a new type of natural antimicrobial packaging material for the preservation of chilled pork. Full article

Simultaneously inhibiting beta-amyloid protein (Aβ) aggregation and reducing metal ion overload in the brain is a promising strategy for treating Alzheimer’s disease (AD). Aloe emodin (AE) is one of the major components of the traditional Chinese medicine rhubarb. Based on its reported pharmacological effects and its structural affinity for metal ions, this study aims to explore the potential of AE in improving AD pathology. Through the injection of Aβ or copper-Aβ complex in the bilateral hippocampus of rats, we constructed two kinds of nontransgenic animal models. Behavioral tests were used to evaluate cognitive impairment, and the effects of AE on neuronal damage and Aβ deposition were measured via Nissl staining and immunohistochemistry. Furthermore, we detected copper content in the serum and brain tissues as well as some biochemical indexes of Aβ cascade pathology in the brain tissues of model rats to explore the mechanism of action. AE treatment decreased copper accumulation and regulated Aβ metabolism in the brain of model rats, thereby improving Aβ deposition, memory impairment, hippocampal nerve cell damage, and related biochemical indicators. AE ameliorated the AD pathology of the model rats by targeting copper-induced Aβ toxicity, revealing a mechanism of action by which AE may exhibit good clinical efficacy in treating AD. Full article

The impairment of neural crest cells (NCCs) plays a pivotal role in the pathogenesis of fetal alcohol spectrum disorders (FASD). Epigenetic regulators mediate ethanol-induced disruptions in NCC development and represent promising targets for nutritional interventions. Here, we developed a biologically informed machine learning framework to predict nutritional supplements that modulate five key epigenetic regulators (miR-34a, DNMT3a, HDAC, miR-125b, and miR-135a) and mitigate ethanol’s adverse effects on NCCs. The optimized models demonstrated robust predictive performance and identified a number of nutritional supplements that could attenuate ethanol-induced NCC impairment, including resveratrol, vitamin B12, emodin, quercetin, and broccoli sprout-derived compounds. Our optimized models also revealed structural features that are critical for mitigating ethanol-induced NCC impairment through specific epigenetic mechanisms. These findings support predictive modeling as a tool to prioritize nutritional supplements for further investigation and the development of dietary strategies to prevent or reduce the risk of FASD. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant clinical challenge due to its multidrug resistance, particularly to β-lactam antibiotics. This study comprehensively evaluated the natural compound emodin for its anti-MRSA activity, mechanisms of action, and potential for synergy with β-lactam antibiotics. Our findings demonstrate that emodin dose-dependently inhibits MRSA growth and abrogates biofilm formation at 2× MIC. Mechanistic studies revealed that emodin compromises cell membrane and wall integrity, induces oxidative stress, and downregulates the virulence factors SPA and EsxA. Furthermore, emodin acted synergistically with β-lactam antibiotics: it enhanced the ability of cefalexin to block bacterial adhesion and invasion of HaCat cells, and potentiated the efficacy of amoxicillin in clearing MRSA from infected macrophages. In conclusion, emodin employs a multi-target mechanism against MRSA and can resensitize the bacterium to conventional β-lactam antibiotics, presenting a promising strategy for combination therapy that may help curb antibiotic use and resistance development. Full article

Antimicrobial resistance (AMR) poses a global health threat, which is becoming more challenging due to the involvement of bacterial virulence mechanisms such as quorum sensing (QS) and biofilm formation. These systems regulate pathogenic traits and shield bacteria from conventional therapies. Phytocompounds offer promising antivirulence strategies by disrupting QS and biofilms without exerting selective pressure. In this study, emodin, a natural anthraquinone, was evaluated for its anti-QS and antibiofilm efficacy. Emodin inhibited violacein production by 63.86% in C. violaceum 12472. In P. aeruginosa PAO1, it suppressed pyocyanin (68.04%), pyoverdin (48.79%), exoprotease (58.55%), elastase (43.13%), alginate (74.12%), and rhamnolipids (56.37%). In S. marcescens MTCC 97, emodin reduced prodigiosin (55.94%), exoprotease (48.80%), motility (83.27%), and cell surface hydrophilicity (41.20%). Biofilm formation was inhibited by over 50% in all three bacteria, highlighting emodin’s potential as a broad-spectrum antibiofilm agent. Molecular docking analyses indicated that emodin exhibited affinity towards QS regulatory proteins CviR, LasR, and SmaR, implying a possible competitive interaction at their ligand-binding sites. Subsequent molecular dynamics simulations confirmed these observations by demonstrating structural stability in emodin-bound proteins. The collective insights from in vitro assays and computational studies underscore the potential of emodin in interfering with QS-mediated virulence expression and biofilm development. Such findings support the exploration of non-antibiotic QS inhibitors as therapeutic alternatives for managing bacterial infections and reducing dependence on traditional antimicrobial agents. Full article

Objective: This study aimed to optimize the extraction of bioactive compounds from Polygonum cuspidatum Sieb. et Zucc. (P. cuspidatum) by evaluating the effect of ethanol concentration. Methods: Ultrasonic extraction was performed using ethanol concentrations of 0%, 30%, 50%, and 70%, and the resulting extracts were assessed for their chemical composition and multifunctional bioactivities. Results: The 70% Ethanol extract exhibited the highest total polyphenol and flavonoid contents and demonstrated the most potent antioxidant, enzyme-inhibitory, and antimicrobial activities, with significant differences (p < 0.05) compared to other concentrations. Chemical analysis identified tannic acid, emodin, and a variety of phenolic compounds as the primary bioactive constituents. Structural analyses using Field Emission Scanning Electron Microscopy (FE-SEM) and Fourier Transform Infrared (FT-IR) Spectroscopy revealed that 70% Ethanol induced the most pronounced structural changes to the cell wall, while FT-IR analysis confirmed the presence of O-H, C=O, C=C, and C-O functional groups, providing a mechanistic basis for the superior extraction efficiency and bioactivity. Conclusions: Ethanol concentration is a critical determinant for maximizing the bioactivity of P. cuspidatum. Extraction with 70% ethanol is identified as the optimal condition, supporting the potential of this plant as a source of natural bioactive compounds. Full article