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Emodin, a natural anthraquinone derivative, is an active ingredient in many Chinese traditional herbs. Interestingly, although it is generally considered to possess hepatoprotective activity, some studies have also reported that it has a certain degree of hepatotoxicity. Additionally, the underlying metabolic regulation of emodin remains uncertain. Therefore, we conducted a nontargeted metabolomic study based on UHPLC/Q-Orbitrap-MS and NMR. Data are available via ProteomeXchange with the identifier PXD055000. The results indicated a close association between the short-term administration of emodin and lipid metabolism. Moreover, a lipidomics investigation utilizing QTRAP 6500+ UHPLC-MS/MS was conducted, with a focus on determining the position of CâC double bonds in unsaturated lipids based on Paternò-Büchi (PB) reaction to discover the metabolic disturbance more precisely. Specifically, lipidomics revealed elevated levels of free fatty acids (FFA) alongside notable reductions in sphingomyelin (SM) and triacylglycerol (TAG) levels. Furthermore, the combination of PB reaction and molecular biology results indicated that short-term administration of emodin may lead to the accumulation of n-6 polyunsaturated fatty acids by up-regulating the expression of FASN, stearyl CoA desaturase 1 (SCD1), and cytosolic phospholipase A 2 (cPLA2). Simultaneously, up-regulation of cyclooxygenase-2 (Cox-2) expression was observed, potentially fostering the production of prostaglandin E2 (PGE2) and subsequent inflammation.
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Introduction: Inflammatory bowel disease (IBD) is a global health concern. Aloe-emodin (AE) has diverse pharmacological benefits, including anti-inflammatory effects. However, its role in IBD remains unclear, prompting our investigation of its regulatory effects and mechanisms in an IBD mouse model. Methods: We studied the therapeutic efficacy of AE in alleviating symptoms and modulating cytokine secretion in a murine model of dextran sulfate sodium (DSS)-induced colitis. BALB/c mice were administered DSS to induce colitis and were subsequently treated with varying doses of AE. Changes in body weight, fecal lipocalin-2 (LCN2) levels, colon tissue histology, and serum cytokine concentrations were evaluated to assess the effects of AE treatment. Additionally, 16 S rRNA sequencing was used to analyze alterations in the composition of the gut microbiota following AE intervention. Finally, the database was used to analyze the signaling pathways associated with IBD in AE and to detect the expression levels of interleukin (IL)-4 pathway using real-time quantitative reverse transcription PCR. Exogenous IL-4 was used in rescue experiments to observe its effects on the disease process of IBD under AE regulation. Results: AE treatment resulted in a dose-dependent mitigation of weight loss, reduction in fecal LCN2 levels, and amelioration of histological damage in DSS-induced colitis in mice. The levels of superoxide dismutase and catalase increased, whereas malondialdehyde decreased following AE treatment, indicating a dose-dependent alleviation of colitis symptoms. Furthermore, AE administration attenuated the secretion of pro-inflammatory cytokines, including IL-17, tumor necrosis factor-alpha (TNF-α), and chemokine ligand 1, while promoting the expression of anti-inflammatory cytokines IL-4 and IL-13. Analysis of the gut microbiota revealed that AE effectively suppressed the overgrowth of colitis-associated bacterial species and restored microbial homeostasis. Finally, we found that overexpression of IL-4 was able to reverse the therapeutic effect of AE for DSS-induced IBD. Conclusion: AE shows promise in alleviating colitis severity, influencing inflammatory cytokines, and modulating the gut microbiota in an IBD mouse model via the IL-4/IL-13 pathway, suggesting its potential as a natural IBD remedy.
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AIMS: This study evaluates the therapeutic potential of emodin in enhancing the anti-inflammatory phenotype of macrophages, proposing a novel treatment strategy for myocardial infarction (MI). Our objective is to overcome the challenge of myocardial repair post-MI by developing an innovative in-situ myocardial drug delivery system that reduces associated hepatotoxicity. MATERIALS AND METHODS: Through network pharmacology, it was identified that emodin primarily treats MI through anti-inflammatory actions. We investigated the influence of emodin on macrophage polarization using cellular assays and examined its therapeutic impacts and hepatotoxicity in animal models across various doses. A novel in-situ drug delivery system was devised using Pluronic F-127, a thermosensitive hydrogel, to enhance solubility and enable localized delivery to the myocardium. KEY FINDINGS: In vitro studies confirmed that emodin effectively induces macrophage polarization toward an anti-inflammatory phenotype. In vivo analyses demonstrated a dose-dependent therapeutic effect on the myocardium, although higher doses led to significant hepatotoxicity. The innovative drug delivery system increased emodin's solubility, facilitated precise myocardial targeting, and markedly reduced systemic exposure and liver toxicity. SIGNIFICANCE: This study introduces an advanced approach to treating MI by leveraging the natural anti-inflammatory properties of emodin combined with drug delivery technology. This strategy not only enhances the clinical feasibility of emodin for MI treatment but also represents a significant advancement in therapeutic methods. It focuses on increasing the drug concentration in the myocardium while minimizing the systemic side effects of the drug.
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Sistemas de Liberación de Medicamentos , Emodina , Hidrogeles , Infarto del Miocardio , Poloxámero , Animales , Emodina/farmacología , Emodina/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Poloxámero/química , Ratones , Masculino , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Humanos , Células RAW 264.7 , Miocardio/metabolismo , Miocardio/patologíaRESUMEN
The growing utilization of Traditional Chinese Medicine (TCM) has resulted in an increase in wastewater. Herein, a new kind of organic-inorganic redox mediator membrane by immobilizing γ-FeO(OH) and aloe-emodin(AE) with the characteristic large π-conjugation anthraquinone structure on PVDF membrane was innovatively achieved. AE exhibiting both electron deficiency and redox activity possesses a co-catalyst role in degradation of tannic acid (TA), aiding in the separation of charge carriers through the sequential hydrogenation and dehydrogenation of AE. The removal rates of TA were 92.8 % in the tannic acid solution and 60.3 % in the simulated rhubarb wastewater by the AE-γ-FeO(OH) membrane under PMS+Vis conditions in 45 min. Also, they show a higher recovery of pure water flux and owning good fouling performance. Overall, this current work presents a novel approach for the design and preparation of organic-inorganic photocatalytic composite membrane using readily available natural products for the purification TCM wastewater.
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Antraquinonas , Membranas Artificiales , Oxidación-Reducción , Taninos , Contaminantes Químicos del Agua , Taninos/química , Antraquinonas/química , Catálisis , Contaminantes Químicos del Agua/química , Aguas Residuales/química , Purificación del Agua/métodos , Rheum/química , Eliminación de Residuos Líquidos/métodos , PolifenolesRESUMEN
Emodin is an important anthraquinone compound with good anti-inflammatory activity in Chinese traditional medicine rhubarb. Detailed spatial distribution information in bio-tissues plays an important role in revealing the pharmacodynamics, toxicology and chemical mechanism of emodin. Herein, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) analytical method was established to obtain information on the spatial and temporal changes of emodin in multiple mouse tissue sections (heart, liver, spleen, lung, kidney, and brain) after intraperitoneal injection of emodin in mice. The measurements were accomplished in the negative ion mode in the range of m/z 250-285 Da with a spatial resolution on 40 µm. It was found that emodin was predominantly distributed in the arteriolar vascular region of the heart, the capsule region of the spleen, and the cortex of the kidney. Moreover, the MALDI-TOF-MSI result implied that emodin might be distributed in the brain. These more detailed spatial distribution information provides the significant reference for investigating the action mechanism of emodin, which cannot be obtained from conventional LC-MS analysis. The distribution trend of emodin in the results of MALDI-TOF-MSI analysis agreed with the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) results well, demonstrating the complementarity and reliability of the established MALDI-TOF-MSI method. Our work provided a label-free molecular imaging method to investigate the precise spatial distribution of emodin in various organs, which prove great potential in studying the effective substances and mechanism of rhubarb.
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Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, primarily due to the intrinsic development of chemoresistance. The most apparent histopathological feature associated with chemoresistance is the alterations in extracellular matrix (ECM) proteins. Natural dietary botanicals such as berberine (BBR) and emodin (EMO) have been shown to possess chemo-preventive potential by regulating ECM in various cancers. Herein, we further investigated the potential synergistic effects of BBR and EMO in enhancing anticancer efficacy by targeting ECM proteins in pancreatic cancer. Genomewide transcriptomic profiling identified that LAMB3 was significantly upregulated in PDAC tissue and highly associated with poor overall survival (OS, hazard ratio [HR], 2.99, 95 % confidence interval [CI], 1.46-6.15; p = 0.003) and progress-free survival (PFS, HR, 2.59; 95 % CI, 1.30-5.18; p = 0.007) in PDAC. A systematic series of functional experiments in BxPC-3 and MIA-PaCa-2 cells revealed that the combination of BBR and EMO exhibited synergistic anti-tumor potential, as demonstrated by cell proliferation, clonogenicity, migration, and invasion assays (p < 0.05-0.001). The combination also altered the expression of key proteins involved in apoptosis, EMT, and EGFR/ERK1,2/AKT signaling. These findings were further supported by patient-derived organoids (PDOs), where the combined treatment resulted in fewer and smaller organoids compared to each compound individually (p < 0.05-0.001). Our results suggest that BBR combined with EMO exerts synergistic anti-cancer effects by modulating the EGFR-signaling pathway through interference with LAMB3 in PDAC.
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Urushiol-induced allergic contact dermatitis (ACD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to pruritus and eczematous lesions. ACD is triggered by immune imbalance. Aloe emodin is an anthraquinone derivative extracted from rhubarb, aloe and other traditional Chinese medicines. It has a wide range of pharmacological effects, including anti-inflammatory, anti-tumor, and anti-allergic effects. The purpose of our study was to demonstrate the effectiveness of aloe-emodin on urushiol-induced acute pruritus and allergic contact dermatitis. The results showed that urushiol could stimulate keratinocytes to release chemokines CXCL1, CXCL2, CCL2, TSLP, and TNF-α, which recruit or activate mast cells. Aloe-emodin treatment inhibited inflammatory-response-induced mast cell degranulation in skin lesions and suppressed the expression of inflammatory cytokines, such as interleukin-4, and interleukin-6. Therefore, the results indicate that aloe-emodin can improve urushiol-induced acute pruritus and allergic contact dermatitis in mice by inhibiting mast cell degranulation.
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Objectives: Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of Polygonum multiflorum on cognitive function. Methods: This study focused primarily on the effects of Polygonum multiflorum and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer's disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind Polygonum multiflorum's impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at Polygonum multiflorum's effects on cognitive decline and AD. Results: According to recent research, Poligonum multiflorum and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis. Conclusion: This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of Polygonum multiflorum. We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders.
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BACKGROUND: Macrophages are the main inflammatory cells involved in kidney injury and play a significant role in the development of acute kidney injury (AKI) and progression of chronic kidney disease (CKD). Emodin is believed to stabilize macrophage homeostasis under pathological conditions. The objective of this study aimed to explore the underlying mechanisms and effects of Emodin on M1 macrophages. METHODS: Network pharmacology methods were used to predict target proteins associated with renal injury and identify the pathways affected by emodin. RAW264.7 macrophages were induced into M1 polarization using LPS and then treated with emodin at 20, 40, and 80 µM. The effects of emodin on cell viability, cytokines (IL-1ß, IL-6, TNF-α), M1 macrophage markers (F4/80 + CD86+), and the EGFR/MAPK pathway were evaluated. Additionally, we transfected RAW264.7 cells with an EGFR shRNA interference lentivirus to assess its effects on RAW264.7 cells function and MAPK pathway. After RAW264.7 cells were passaged to expanded culture and transfected with EGFR-interfering plasmid, macrophages were induced to polarize towards M1 with LPS and then treated with 80 µM emodin. CKD modeling was performed to test how emodin is regulated during CKD. RESULTS: There are 15 common targets between emodin and kidney injury, of which the EGFR/MAPK pathway is the pathway through which emodin affects macrophage function. Emodin significantly reduced the levels of IL-6, IL-1ß and TNF-α (p < 0.05) and the ratio of M1 macrophage surface markers F4/80 + CD86+ (p < 0.01) in the supernatant of RAW264.7 cells in a dose-dependent manner. Furthermore, the inhibitory effect of emodin on RAW264.7 cells was achieved by interfering with the EGFR/MAPK pathway. Moreover, emodin also affected the mRNA and protein expression of EGFR and Ras, leading to a decrease in the rate of M1 macrophages, thus inhibiting the pro-inflammatory effect of M1 macrophages. The addition of emodin reduced the rate of M1 macrophages in CKD and inhibited the further polarization of M1 macrophages, thus maintaining the pro-inflammatory and anti-inflammatory homeostasis in CKD, and these effects were achieved by emodin through the control of the EGRF/ERK pathway. CONCLUSION: Emodin attenuates M1 macrophage polarization and pro-inflammatory responses via the EGFR/MAPK signalling pathway. And the addition of emodin maintains pro- and anti-inflammatory homeostasis, which is important for maintaining organ function and tissue repair.
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Lesión Renal Aguda , Emodina , Receptores ErbB , Sistema de Señalización de MAP Quinasas , Activación de Macrófagos , Macrófagos , Insuficiencia Renal Crónica , Animales , Ratones , Emodina/farmacología , Receptores ErbB/metabolismo , Receptores ErbB/genética , Células RAW 264.7 , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología , Activación de Macrófagos/efectos de los fármacos , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Citocinas/metabolismo , Citocinas/genéticaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: HLA-B*35:01 has been identified as a risk allele for Polygonum multiflorum Thunb.-induced liver injury (PMLI). However, the immune mechanism underlying HLA-B*35:01-mediated PMLI remains unknown. AIM OF THE STUDY: To characterize the immune mechanism of HLA-B*35:01-mediated PMLI. MATERIALS AND METHODS: Components of P. multiflorum (PM) bound to the HLA-B*35:01 molecule was screened by immunoaffinity chromatography. Both wild-type mice and HLA-B*35:01 transgenic (TG) mice were treated with emodin. The levels of transaminases, histological changes and T-cell response were assessed. Splenocytes from emodin-treated mice were isolated and cultured in vitro. Phenotypes and functions of T cells were characterized upon drug restimulation using flow cytometry or ELISA. Emodin-pulsed antigen-presenting cells (APCs) or glutaraldehyde-fixed APCs were co-cultured with splenocytes from emodin-treated transgenic mice to detect their effect on T-cell activation. RESULTS: Emodin, the main component of PM, could non-covalently bind to the HLA-B*35:01-peptide complexes. TG mice were more sensitive to emodin-induced immune hepatic injury, as manifested by elevated aminotransferase levels, infiltration of inflammatory cells, increased percentage of CD8+T cells and release of effector molecules in the liver. However, these effects were not observed in wild-type mice. An increase in percentage of T cells and the levels of interferon-γ, granzyme B, and perforin was detected in emodin-restimulated splenocytes from TG mice. Anti-HLA-I antibodies inhibited the secretion of these effector molecules induced by emodin. Mechanistically, emodin-pulsed APCs failed to stimulate T cells, while fixed APCs in the presence of emodin could elicit the secretion of T cell effector molecules. CONCLUSION: The HLA-B*35:01-mediated CD8+ T cell reaction to emodin through the P-I mechanism may contribute to P. multiflorum-induced liver injury.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Emodina , Fallopia multiflora , Animales , Humanos , Masculino , Ratones , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Emodina/farmacología , Fallopia multiflora/química , Granzimas/metabolismo , Granzimas/genética , Antígeno HLA-B35 , Interferón gamma/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/inmunología , Hígado/metabolismo , Activación de Linfocitos/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Transgénicos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
BACKGROUND: Polygonum multiflorum (PM) is a core herb that enhances immunity. It can also detoxify, reduce swelling, and intercept malaria. Its main components, emodin (EMD) and 2,3,5,4'-Tetrahydroxy stilbene-2-O-ß-D-glucoside (stilbene glycoside, TSG), have good anti-cancer potential. PURPOSE: The study aims to investigate synergic effects of EMD and TSG on CRC and its possible mechanism. METHODS: Network pharmacology and bioinformatics were used to identify targets. HPLC was used to analyze the effective ingredients in PM and to determine the content of the main ingredients. HT-29 cells were used for in vitro experiments. Cell Counting Kit-8 (CCK8) and scratch test were used to detect the effects of various chemical components of PM on the proliferation and migration of HT-29 cells, and Western Bolt (WB) test was used to evaluate the effects of EMD and TSG on P53 pathway. In vivo experiments, the effects of EMD and TSG were evaluated by measuring tumor weight and tumor volume in CRC mice model and histological analysis were carried out with HE staining. The expressions of HSP90, P53, COX2, and ROS were detected by quantitative reverse transcription polymerase chain reaction (PCR), and IL-1ß, IL-4, IL-6, IL-10, TGF-ß and IFN-γ were detected by enzyme linked immunosorbent assay (ELISA). WB and Immunohistochemistry (IHC) were used to detect the expression of P53 related proteins. RESULTS: Network pharmacology showed PM closely related to colorectal cancer pathway and the core targets included STAT3 and P53; bioinformatics indicated P53 played an important role in the development and prognosis of CRC; chemical analysis showed identified and quantified gallic acid (GA), cis-TSG, trans-TSG, Emodin glucoside(EMDG), physcion glucoside (PHYG), EMD in PM; EMD induced apoptosis and TSG inhibited migration of HT-29 cells; EMD and TSG could coordinately shrink tumor size of CRC mice, elevate expressions of F4/80, decrease the content of IL-6 and TGF-ß, promote tumor oxidized and reduce expression of P53 and STAT3 in the tumor. CONCLUSIONS: In vitro experiments showed that TSG inhibited cancer cell migration and EMD induced apoptosis. EMD and TSG had synergic effects on CRC, whose possible mechanism might be to regulate the expression of cytokines and inhibit P53 pathway.
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Proliferación Celular , Neoplasias Colorrectales , Emodina , Glucósidos , Factor de Transcripción STAT3 , Estilbenos , Emodina/farmacología , Animales , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Estilbenos/farmacología , Células HT29 , Glucósidos/farmacología , Proliferación Celular/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Ratones , Movimiento Celular/efectos de los fármacos , Fallopia multiflora/química , Antineoplásicos Fitogénicos/farmacología , Sinergismo Farmacológico , Ratones Desnudos , Ratones Endogámicos BALB C , Farmacología en Red , Masculino , Glicósidos/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis/efectos de los fármacosRESUMEN
Emodin (EMO) has the effect of anti-cholestasis induced by alpha-naphthylisothiocyanate (ANIT). But its mechanism is still unclear. The farnesoid X receptor (Fxr) is the master bile acid nuclear receptor. Recent studies have reported that Sirtuin 1 (Sirt1) can regulate the activities of Fxr. The purpose of the current study was to investigate the mechanism of EMO against ANIT-induced liver injury based on Sirt1/Fxr signaling pathway. The ANIT-induced cholestatic rats were used with or without EMO treatment. Serum biochemical indicators, as well as liver histopathological changes were examined. The genes expressions of Sirt1, Fxr, Shp, Bsep and Mrp2 were detected. The expressions of Sirt1, Fxr and their downstream related genes were investigated in vitro. The results showed that EMO significantly alleviated ANIT-induced liver injury in rats, and increased Sirt1, Fxr, Shp, Bsep and Mrp2 gene expression in liver, while decreased the expression of Cyp7a1. EMO significantly activated Fxr, while Sirt1 inhibitor and Sirt1 gene silencing significantly reduced Fxr activity in vitro. Collectively, EMO in the right dose has a protective effect on liver injury induced by ANIT, and the mechanism may be through activation of Fxr by Sirt1, thus regulating bile acid metabolism, and reducing bile acid load in hepatocytes.
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1-Naftilisotiocianato , Colestasis , Emodina , Receptores Citoplasmáticos y Nucleares , Transducción de Señal , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal/efectos de los fármacos , Emodina/farmacología , Emodina/uso terapéutico , Colestasis/metabolismo , Colestasis/tratamiento farmacológico , Colestasis/patología , Ratas , Masculino , 1-Naftilisotiocianato/toxicidad , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/lesiones , Ácidos y Sales Biliares/metabolismo , Humanos , Ratas Sprague-Dawley , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2RESUMEN
Emodin is a naturally occurring anthraquinone derivative and serves as an active component in various traditional Chinese herbal medicines. It is widely known for its broad pharmacological effects, including anti-inflammatory, antioxidant, and anticancer properties. However, high doses and long-term use of emodin can also lead to liver toxicity. Nevertheless, the mechanism of emodin-induced liver toxicity remains unclear at present. This article aims to summarize the toxicological research progress on emodin, with a particular focus on elucidating the mechanisms underlying emodin-induced hepatocyte injury. By providing essential information, the study intends to facilitate further research and safe usage of emodin for researchers and clinical practitioners.
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AIMS: This study aimed to determine the preventive effects of emodin on cyclophosphamide (CYP)-induced cystitis and to explore the molecular mechanism. METHODS: In vivo, mice were modeled by CYP. Before a half hour of CYP treatment, Jumonji domain-containing protein-3 (JMJD3) inhibitors (GSK-J4) and emodin were used to treat CYP model mice. Bladder samples were stained for hematoxylin-eosin and toluidine blue. Next, JMJD3 was quantified by immunofluorescence staining, RT-PCR, and Western blot. CXCR3 was quantified by Western blot and ELISA. In vitro, before stimulated by lipopolysaccharide (LPS), human bladder smooth muscle cells (hBSMCs) were transfected with pcDNA3.1-JMJD3 plasmids, shRNA-JMJD3 plasmids or pretreated with emodin. Collected cells to detect JMJD3 and CXCR3 ligands again; collected supernatant of culture for Transwell assay. Finally, as the JAK2 inhibitor, AG490 was used to pretreat LPS-induced hBSMCs. Western blot was performed to quantify proteins. RESULTS: Emodin inhibited mast cell migration and suppressed the expression of JMJD3, CXCR3, and CXCR3 ligands, not only in vivo but also in vitro. The pharmacological effects of emodin were similar to GSK-J4 or JMJD3 inhibition. In addition, emodin significantly downregulated the phosphorylation of JAK2 and STAT3, and inhibited JMJD3/CXCR3 axis transduction like AG490. CONCLUSION: Emodin has a preventive effect on cystitis by inhibiting mast cell migration through inhibition of the JAK2/STAT3/JMJD3/CXCR3 signaling pathway.
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The present study examined the potential neuroprotective effects of aloe-emodin (AE) nanoparticles on the cerebral stroke-associated target protein myeloperoxidase (MPO). We investigated the binding interactions between AE and MPO through molecular docking and molecular dynamics simulations. Molecular docking results indicated that AE exhibited a binding energy of -6.9 kcal/mol, whereas it was -7.7 kcal/mol for 2-{[3,5-bis(trifluoromethyl)benzyl]amino}-n-hydroxy-6-oxo-1,6-dihydropyrimidine-5-carboxamide (CCl). Furthermore, molecular dynamics studies demonstrated that AE possesses a stronger binding affinity (-57.137 ± 13.198 kJ/mol) than does CCl (-22.793 ± 30.727 kJ/mol), suggesting that AE has a more substantial inhibitory effect on MPO than does CCl. Despite the therapeutic potential of AE for neurodegenerative disorders, its bioavailability is limited within the body. A proposed hypothesis to enhance the bioavailability of AE is its conversion into aloe-emodin nanoparticles (AENP). The AENPs synthesized through a fabrication method were spherical with a consistent diameter of 104.4 ± 7.9 nm and a polydispersity index ranging from 0.525 to 0.586. In rats experiencing cerebral stroke, there was a notable increase in cerebral infarction size; abnormalities in electrocardiogram (ECG) and electroencephalogram (EEG) patterns; a decrease in brain and cardiac antioxidant activities; and an increase in myeloperoxidase levels compared to those in normal rats. Compared with AE treatment, AENP treatment significantly ameliorated cerebral infarction, normalized ECG and EEG patterns, enhanced brain and cardiac antioxidant activities, and reduced MPO levels in stroke rats. Histopathological evaluations revealed pronounced alterations in the rat hippocampus, with pyknotic nuclei, disarray and loosely packed cells, deterioration of cardiac muscle fibers, and extensive damage to cardiac myocytes, in contrast to those in normal rats. AENP treatment mitigated these pathological changes more effectively than AE treatment in both brain and cardiac cells. These findings support that AENP provides considerable protection against stroke-associated myocardial infarction.
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Resumen: El gel de Aloe vera es considerado una fuente natural de múltiples beneficios, originados por la acción combinada de vitaminas, aminoácidos, compuestos fenólicos, enzimas, minerales, ácidos orgánicos, lípidos y carbohidratos, que se relacionan con la mejora de enfermedades neuro-degenerativas como Alzheimer. Los ensayos in vitro e in silico permiten confirmar e identificar posibles beneficios de esta planta y sus compuestos en enfermedades. El objetivo del presente trabajo fue evaluar la actividad antioxidante del gel de A. vera y mediante análisis in silico, establecer el potencial terapéutico de sus compuestos bioactivos en la enfermedad de Alzheimer. Se obtuvieron hojas de A. vera, de las que se extrajo el gel, retirando el exocarpio, se liofilizó y almacenó hasta su uso. Se caracterizó la capacidad antioxidante, se cuantificaron los compuestos fenólicos y flavonoides y se analizó la relación que existe entre los parámetros mediante correlación de Pearson. Mediante análisis in silico se evaluó el potencial de interacción de 8 compuestos del gel con la proteína gamma secretasa. El gel de A. vera obtuvo alta capacidad antioxidante por ABTS, DPPH, radical OH y poder reductor, usando bajas concentraciones para inhibir el 50 % de los radicales, y correlaciones positivas con fenoles totales y flavonoides. En el estudio in silico el compuesto que presentó mejor unión con gamma secretasa fue aloe-emodina, con menor energía libre de unión y menor concentración de constante de inhibición, sugiriendo su potencial uso como coadyuvante en el tratamiento de la enfermedad de Alzheimer.
Abstract: Aloe vera gel is considered a natural source of multiple benefits, originated by the combined action of vitamins, amino acids, phenolic compounds, enzymes, minerals, organic acids, lipids and carbohydrates, which are related to the improvement of neuro-degenerative diseases such as Alzheimer's. In vitro and in silico tests allow us to confirm and identify possible benefits of this plant and its compounds in diseases. The objective of the present study was to evaluate the antioxidant activity of A. vera gel and, through in silico analysis, to establish the therapeutic potential of its bioactive compounds in Alzheimer's disease. A. vera leaves were obtained, from which the gel was extracted, removing the exocarp, lyophilized and stored until use. The antioxidant capacity was characterized, the phenolic compounds and flavonoids were quantified, and the relationship between the parameters was analyzed using Pearson correlation. The interaction potential of 8 compounds in the gel with the gamma secretase protein was evaluated through in silico analysis. The A. vera gel obtained high antioxidant capacity due to ABTS, DPPH, OH radical and reducing power, using low concentrations to inhibit 50 % of the radicals, and positive correlations with total phenols and flavonoids. In the in silico study, the compound that showed the best binding with gamma secretase was aloe-emodin, with lower binding free energy and lower inhibition constant concentration, suggesting its potential use as an adjuvant in the treatment of Alzheimer's disease.
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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.
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Neonatal hypoxic-ischemic brain damage (HIBD) can lead to mortality and severe neurological dysfunction. Emodin is a natural anthraquinone derivative that is easy to obtain and has good neuroprotective effects. This study aimed to investigate the neuroprotective effect of emodin on neonatal mouse HIBD. The modified Rice-Vannucci method was used to induce HIBD in mouse pups. Eighty postnatal 7-day (P7) C57BL/6 neonatal mice were randomly divided into the sham group (sham), vehicle group (vehicle), and emodin group (emodin). TTC staining and whole-brain morphology were used to evaluate the infarct volume and morphology of the brain tissue. The condition of the neurons was observed through Nissl staining, HE staining, FJC staining, immunofluorescence and Western blot for NeuN, IBA-1, and GFAP. The physiological status of the mice was evaluated using weight measurements. The neural function of the mice was assessed using the negative geotaxis test, righting reflex test, and grip test. TUNEL staining was used to detect apoptosis in brain cells. Finally, Western blot and immunofluorescence were used to detect the expression levels of apoptosis-related proteins, such as P53, cleaved caspase-3, Bax and Bcl-2, in the brain. Experiments have shown that emodin can reduce the cerebral infarct volume, brain oedema, neuronal apoptosis, and degeneration and improve the reconstruction of brain tissue morphology, neuronal morphology, physiological conditions, and neural function. Additionally, emodin inhibited the expression of proapoptotic proteins such as P53, Bax and cleaved caspase-3 and promoted the expression of the antiapoptotic protein Bcl-2. Emodin attenuates HIBD by inhibiting neuronal apoptosis in neonatal mice.
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Animales Recién Nacidos , Apoptosis , Encéfalo , Emodina , Hipoxia-Isquemia Encefálica , Ratones Endogámicos C57BL , Neuronas , Fármacos Neuroprotectores , Animales , Emodina/farmacología , Apoptosis/efectos de los fármacos , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/patología , Hipoxia-Isquemia Encefálica/metabolismo , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/metabolismo , Ratones , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. RESULTS: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-ß/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. CONCLUSION: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.
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Fibrosis , Microbioma Gastrointestinal , Riñón , Nanopartículas , Ratas Sprague-Dawley , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Administración Oral , Masculino , Riñón/patología , Riñón/efectos de los fármacos , Nanopartículas/química , Microgeles/química , Lacticaseibacillus casei , Probióticos/farmacología , Insuficiencia Renal Crónica/tratamiento farmacológico , Quitosano/química , Alginatos/química , Triterpenos Pentacíclicos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Distribución Tisular , Pared CelularRESUMEN
Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.