Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.620
Filtrar
1.
Pancreas ; 51(7): 739-746, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36395397

RESUMO

OBJECTIVES: Because the pathogenesis of the disease is unclear, the treatment of patients with acute pancreatitis, especially severe acute pancreatitis, is still a major challenge for clinicians. Emodin is an anthraquinone compound extracted from rhubarb that can alleviate the damage to pancreatic ductal epithelial cells induced by adenosine triphosphate, but whether it has a similar protective effect on sodium taurocholate (STC)-stimulated pancreatic ductal cells and the underlying mechanism has not yet been reported. METHODS: A model of STC-induced HPDE6-C7 human pancreatic ductal epithelial cell injury was established, and then apoptosis and the levels of reactive oxygen species (ROS), glutathione, gamma-glutamylcysteine synthetase, and inflammatory cytokines were assessed in the presence or absence of emodin pretreatment. S100 calcium binding protein A9 (S100A9) and Vanin1 (VNN1) protein expression was also measured. RESULTS: Emodin significantly increased HPDE6-C7 cell viability, inhibited apoptosis and ROS release, and elevated glutathione levels and gamma-glutamylcysteine synthetase activity. Furthermore, emodin downregulated S100A9 and VNN1 protein expression and inhibited the production of inflammatory factors, such as interleukin (IL)-1ß, IL-6, IL-8, and IL-18. CONCLUSIONS: Emodin attenuates STC-induced pancreatic ductal cell injury possibly by inhibiting S100A9/VNN1-mediated ROS release. This finding provides evidence for the future development of emodin as a therapeutic agent.


Assuntos
Emodina , Pancreatite , Humanos , Doença Aguda , Emodina/farmacologia , Células Epiteliais/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Glutamato-Cisteína Ligase/farmacologia , Glutationa/farmacologia , Pancreatite/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ácido Taurocólico
2.
Metab Eng ; 74: 130-138, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36328293

RESUMO

Physcion is a characteristic component of the traditional herb rhubarb with diverse pharmacological activities that has been commercially approved as an herbal fungicide. Nevertheless, its extremely low contents, costly purification procedure and geographically restricted planting severely hinder its application. Here, a cell factory was constructed in the filamentous fungus Aspergillus terreus for physcion production via microbial fermentation by integrating a pathway-modified emodin accumulation module and a position-selective emodin methylation module. Specifically, 1.71 g/L emodin accumulated when the transcriptional activator GedR and the emodin-1-OH-O-methyltransferase GedA in the geodin biosynthetic pathway were overexpressed and knocked out, respectively. Subsequently, potential emodin-3-OH-O-methyltransferase candidates were enzymatically screened in vitro and introduced into the emodin-accumulating mutant in vivo to generate a physcion-producing strain showing the highest titre of 6.3 g/L in fed-batch fermentation. Thus, our study provides an alternative strategy for the highly efficient, economical production of physcion and a representative example for microbial synthetic biology.


Assuntos
Emodina , Fungicidas Industriais , Plantas , Metiltransferases , Antraquinonas
3.
Eur J Pharmacol ; 936: 175329, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36341884

RESUMO

Diabetic wound healing, characterized by chronic inflammation, remains a medical challenge. The failure of prompt conversion from pro-inflammatory M1-like macrophage to pro-healing M2-like macrophage is the main obstacle to diabetic wounds. Emodin, an anthraquinone derivative, has multiple bioactivities, including antibacterial, anticancer, and anti-inflammatory. Recently, emodin has shown potential in promoting wound healing. However, the underlying molecular mechanism remains unclear. In this study, we examined the effects of emodin on wound healing in db/db diabetic mice using a full-thickness excision model. Our results showed that emodin can remarkably accelerate healing by enhancing extracellular matrix (ECM) synthesis and granulation tissue formation. We identified 32 potential targets of emodin by network pharmacology analysis, and our transcriptome analysis highlighted the down-regulation of the NF-κB signaling pathway mediated by emodin. Mechanistically, emodin was shown to inhibit the p65-NF-κB complex and promote the proportion of M2 (anti-inflammatory)-like phenotype macrophages both in vitro and vivo. Then, bone-marrow-derived macrophages were co-cultured with fibroblasts (mouse dermal fibroblasts cells). Treatment of emodin significantly increased the proportion of M2-polarized macrophages and the expression level of TGF-ß, a typical ECM formation-related cytokine secreted by the M2 macrophages in the co-cultured supernatant. We further revealed that emodin improved the proliferation of mouse dermal fibroblasts (MDFs) cells and upregulated the expression levels of collagen III, fibronectin and α-SMA in MDFs cells in emodin-treated co-culture systems. 1D11, a neutralizing antibody for all three major TGF-ß isoforms, diminished the biological effects of emodin on proliferation and ECM formation in MDFs cells. Taken together, our study suggests emodin may serve as an effective therapeutic agent for diabetic wounds.


Assuntos
Diabetes Mellitus Experimental , Emodina , Animais , Camundongos , Emodina/farmacologia , Emodina/uso terapêutico , NF-kappa B , Diabetes Mellitus Experimental/tratamento farmacológico , Cicatrização , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Macrófagos , Fator de Crescimento Transformador beta
4.
Appl Environ Microbiol ; 88(21): e0094222, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36226941

RESUMO

Grasses harbor diverse fungi, including some that produce mycotoxins or other secondary metabolites. Recently, Florida cattle farmers reported cattle illness, while the cattle were grazing on warm-season grass pastures, that was not attributable to common causes, such as nutritional imbalances or nitrate toxicity. To understand correlations between grass mycobiome and mycotoxin production, we investigated the mycobiomes associated with five prominent, perennial forage and weed grasses [Paspalum notatum Flügge, Cynodon dactylon (L.) Pers., Paspalum nicorae Parodi, Sporobolus indicus (L.) R. Br., and Andropogon virginicus (L.)] collected from six Florida pastures actively grazed by livestock. Black fungal stromata of Myriogenospora and Balansia were observed on P. notatum and S. indicus leaves and were investigated. High-throughput amplicon sequencing was applied to delineate leaf mycobiomes. Mycotoxins from P. notatum leaves were inspected using liquid chromatography-mass spectrometry (LC-MS/MS). Grass species, cultivars, and geographic localities interactively affected fungal community assemblies of asymptomatic leaves. Among the grass species, the greatest fungal richness was detected in the weed S. indicus. The black fungal structures of P. notatum leaves were dominated by the genus Myriogenospora, while those of S. indicus were codominated by the genus Balansia and a hypermycoparasitic fungus of the genus Clonostachys. When comparing mycotoxins detected in P. notatum leaves with and without M. atramentosa, emodin, an anthraquinone, was the only compound which was significantly different (P < 0.05). Understanding the leaf mycobiome and the mycotoxins it may produce in warm-season grasses has important implications for how these associations lead to secondary metabolite production and their subsequent impact on animal health. IMPORTANCE The leaf mycobiome of forage grasses can have a major impact on their mycotoxin contents of forage and subsequently affect livestock health. Despite the importance of the cattle industry in warm-climate regions, such as Florida, studies have been primarily limited to temperate forage systems. Our study provides a holistic view of leaf fungi considering epibiotic, endophytic, and hypermycoparasitic associations with five perennial, warm-season forage and weed grasses. We highlight that plant identity and geographic location interactively affect leaf fungal community composition. Yeasts appeared to be an overlooked fungal group in healthy forage mycobiomes. Furthermore, we detected high emodin quantities in the leaves of a widely planted forage species (P. notatum) whenever epibiotic fungi occurred. Our study demonstrated the importance of identifying fungal communities, ecological roles, and secondary metabolites in perennial, warm-season grasses and their potential for interfering with livestock health.


Assuntos
Emodina , Micobioma , Micotoxinas , Bovinos , Animais , Poaceae/química , Estações do Ano , Cromatografia Líquida , Espectrometria de Massas em Tandem , Gado , Geografia , Folhas de Planta , Estruturas Fúngicas
5.
Molecules ; 27(20)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36296694

RESUMO

In Tartary buckwheat (Fagopyrum tataricum), the edible parts are mainly grain and sprouts. Tartary buckwheat contains protecting substances, which make it possible for plants to survive on high altitudes and under strong natural ultraviolet radiation. The diversity and high content of phenolic substances are important for Tartary buckwheat to grow and reproduce under unfriendly environmental effects, diseases, and grazing. These substances are mainly flavonoids (rutin, quercetin, quercitrin, vitexin, catechin, epicatechin and epicatechin gallate), phenolic acids, fagopyrins, and emodin. Synthesis of protecting substances depends on genetic layout and on the environmental conditions, mainly UV radiation and temperature. Flavonoids and their glycosides are among Tartary buckwheat plants bioactive metabolites. Flavonoids are compounds of special interest due to their antioxidant properties and potential in preventing tiredness, diabetes mellitus, oxidative stress, and neurodegenerative disorders such as Parkinson's disease. During the processing and production of food items, Tartary buckwheat metabolites are subjected to molecular transformations. The main Tartary buckwheat traditional food products are bread, groats, and sprouts.


Assuntos
Catequina , Emodina , Fagopyrum , Fagopyrum/química , Quercetina/química , Catequina/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Raios Ultravioleta , Emodina/metabolismo , Rutina/química , Flavonoides/química , Glicosídeos/metabolismo
6.
ACS Chem Biol ; 17(10): 2828-2835, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36197945

RESUMO

Genome sequencing of filamentous fungi has demonstrated that most secondary metabolite biosynthetic gene clusters (BGCs) are silent under standard laboratory conditions. In this work, we have established an in vitro CRISPR-Cas9 system in Aspergillus wentii. To activate otherwise silent BGCs, we deleted the negative transcriptional regulator mcrA. Deletion of mcrA (mcrAΔ) resulted in differential production of 17 SMs in total when the strain was cultivated on potato dextrose media (PDA). Nine out of fifteen of these SMs were fully characterized, including emodin (1), physcion (2), sulochrin (3), physcion bianthrone (4), 14-O-demethylsulochrin (5), (trans/cis)-emodin bianthrone (6 and 7), and (trans/cis)-emodin physcion bianthrone (8 and 9). These compounds were all found to be produced by the same polyketide synthase (PKS) BGC. We then performed a secondary knockout targeting this PKS cluster in the mcrAΔ background. The metabolite profile of the dual-knockout strain revealed new metabolites that were not previously detected in the mcrAΔ parent strain. Two additional SMs were purified from the dual-knockout strain and were characterized as aspergillus acid B (16) and a structurally related but previously unidentified compound (17). For the first time, this work presents a facile genetic system capable of targeted gene editing in A. wentii. This work also illustrates the utility of performing a dual knockout to eliminate major metabolic products, enabling additional SM discovery.


Assuntos
Emodina , Policetídeo Sintases/genética , Sistemas CRISPR-Cas/genética , Ribonucleoproteínas , Aspergillus/genética , Família Multigênica , Glucose
7.
Molecules ; 27(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36234685

RESUMO

A series of novel aloe-emodin-coumarin hybrids were designed and synthesized. The antitumor activity of these derivatives was evaluated against five human tumor cell lines (A549, SGC-7901, HepG2, MCF-7 and HCT-8). Some of the synthesized compounds exhibited moderate to good activity against one or more cell lines. Particularly, compound 5d exhibited more potent antiproliferative activity than the reference drug etoposide against all tested tumor cell lines, indicating that it had a broad spectrum of antitumor activity and that it may provide a promising lead compound for further development as an antitumor agent by structural modification. Furthermore, the structure-activity relationship study of the synthesized compounds was also performed.


Assuntos
Aloe , Antineoplásicos , Emodina , Antraquinonas , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Cumarínicos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Emodina/farmacologia , Etoposídeo/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
8.
Molecules ; 27(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36234820

RESUMO

Steaming is a characteristic pharmaceutical skill in Traditional Chinese Medicine (TCM). Polygonum multiflorum radix (PM) and its steamed products have been used in Asia for centuries. Raw Polygonum multiflorum radix (RPM) is commonly used to promote defecation but can exert toxicity, especially in liver injury. However, RPM can be made converted into Polygoni multiflori radix praeparata (PMP) by steaming; this is considered a good method to reduce defecation and liver injury caused by PM in Asia. The chemical constituents of TCM are the key to its action. We systematically analyzed the effect of steaming on PM constituents, defecation, and liver injury. We identified 13 main constituents from PM and PMP; the results showed that after being steamed, two constituents (TSG, catechin) had decreased, six constituents (such as procyanidin B1 or B2) had disappeared, four constituents (such as emodin, physcion) had increased, emodin-8-O-ß-D-glucoside remained unchanged in PMP. Pharmacological experiments showed that PM could promote defecation; however, there were no obvious effects in response to PMP. Only a high dose of PM for 14 days caused some degree of liver injury, although this injury disappeared after 14 days of drug withdrawal. Network pharmacology and molecular docking studies showed that TSG, emodin and physcion were the most effective in promoting defecation and causing liver injury. Collectively, our findings show that steaming can reduce the effect of PM on promoting defecation and reducing liver injury. TSG may be one of the important constituents in PM that can promote defecation and cause liver injury.


Assuntos
Catequina , Medicamentos de Ervas Chinesas , Emodina , Fallopia multiflora , Polygonum , Catequina/farmacologia , Defecação , Medicamentos de Ervas Chinesas/química , Emodina/análogos & derivados , Emodina/farmacologia , Fígado , Simulação de Acoplamento Molecular , Raízes de Plantas/química , Polygonum/química , Vapor/análise
9.
Astrobiology ; 22(10): 1165-1175, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36070545

RESUMO

Anthraquinones are a family of natural products with useful bioactivity and optical properties. An anthraquinone called parietin is produced by extremophiles to protect against solar ultraviolet B radiation, so it is a potential biosignature in astrobiology. Raman spectroscopy, which is now used in space environments, can detect molecules such as parietin based on molecular vibrations. In this study, we show that time-dependent density functional theory (TDDFT) can accurately calculate the Raman spectra of three dihydroxyanthraquinones: parietin, emodin, and chrysophanol. By comparing calculated spectra to measured Raman spectra from purified powders, 10 vibrational modes are identified. The detailed molecular motions of these fused ring vibrations are described, and vibrations modes that are common to all three molecules are highlighted. In addition to powder spectra, Raman measurements from the thallus of Xanthoria parietina, a lichen that produces parietin, are reported, with excellent agreement to both the parietin powder and calculated Raman spectra. These results show that TDDFT calculations could make significant contributions to spectral analysis in the search for biotic organic materials beyond Earth.


Assuntos
Produtos Biológicos , Emodina , Antraquinonas , Emodina/análogos & derivados , Emodina/química , Pós , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Vibração
10.
Biomed Pharmacother ; 153: 113421, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076485

RESUMO

In folk medicine, Aloe, a genus of Aloaceae, is constantly developed into laxative drugs or products and skin remedies with tremendous popularity worldwide. However, almost all products of Aloe are in roughly processed form. Therefore, developing related products of the active ingredients derived from Aloe is of great medical value. Aloin is a quality standard compound based on the Chinese Pharmacopoeia (CHP). It has a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, anti-osteoporotic, organ-protective, anti-viral, anti-microbial, anti-parasitic, and laxative potentials. Moreover, it regulates blood lipids and glucose and improves neuropathic pain effects, depicting potential to be transformed into promising medicines and healthcare products. In addition to the functional cosmetics and health products of Aloe, the availability, pharmacological activities, pharmacokinetics, formulation studies, and toxicity of aloin were summarized after investigating the literature from PubMed, Google, and other databases. Moreover, significant attention had been paid to the development of aloin-derived medicines and healthcare products. Thus, the present review clarified the possibility of aloin as medicines and healthcare products to develop and utilize Aloe resources.


Assuntos
Aloe , Emodina , Antraquinonas/farmacologia , Anti-Inflamatórios , Antivirais , Atenção à Saúde , Emodina/análogos & derivados , Emodina/farmacologia , Laxantes
11.
Biomed Pharmacother ; 153: 113427, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076547

RESUMO

With an poorly characterized pathogenesis, Diabetic encephalopathy (DE), one of the main chronic complications of diabetes, would require further studies. Recent studies have proven that DE developing in conjunction with neuronal apoptosis, which is tightly regulated by a variety of processes and involved with histone acetylation and molecular signaling or so on. Though the histone deacetylase 4 (HDAC4), HDAC5, HDAC7, and HDAC9 form class IIa of the HDAC superfamily have been found participating in multiple neurodegenerative diseases, while JNK signaling pathway activation was hypothesized as a key cause leading to cell apoptosis, the correlation between HDAC4 and JNK signaling pathway remains unknown. Studies have found that Radix Polygoni Multiflori (RPM) contains a variety of ingredients, such as TSG and Emodin, could exert antioxidant effects, scavenge free radicals, inhibit cell apoptosis and provide neuroprotection, but the underlying mechanism has not fully elucidated yet. In the present study, we further explored the mechanism by which RPM improves the cognitive function of diabetic rats. Simultaneously, TSG and Emodin were used to stimulate HT-22 hippocampal neurons treated with high glucose. After RPM extracts or TSG, Emodin treatments, the cognitive functions of DE rats improved while the hippocampal neurons arranged tighter and increased. Meanwhile, the expression level of HAT, HDAC, HDAC4 and JNK signaling pathway and apoptosis related genes were decreased. Our finds indicates that RPM and Emodin would inhibit HDAC4 expression, curb the activation of the JNK pathway, reduce hippocampal neuron apoptosis and ultimately meliorate the cognitive function from diabetes. Additionally, the markedly inhibitory effects of the RPM and Emodin on HAT and HDAC was identified for the first time in this study, which provides a basis for future drug targeting histones acetylation development and application.


Assuntos
Encefalopatias , Diabetes Mellitus Experimental , Emodina , Estilbenos , Animais , Apoptose , Diabetes Mellitus Experimental/tratamento farmacológico , Hipocampo , Histona Desacetilases , Sistema de Sinalização das MAP Quinases , Ratos
12.
Biomed Pharmacother ; 153: 113452, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076566

RESUMO

AIM: The purpose of this study was to investigate the mechanical and electrophysiological effects of emodin on BK channels in the IRASMCs, of the rat. METHODS: Isolated interlobar renal artery was used for vascular reactivity measurements using a pressure myograph system. Electrophysiological measurements of single vascular smooth muscle cells were conducted using whole-cell and cell-attached patch-clamp recording. Laser scanning confocal microscope technology was used to measure cytosolic calcium ion signals. KEY RESULTS: Emodin relaxed the interlobar renal artery and enhanced the outward currents amplitude of IRASMCs in a concentration-dependent manner, and IbTX inhibited these emodin-induced outward currents. Incubation of IRASMCs in a calcium ion free medium for 30 min decreased the observed effects of emodin on IRASMCs membrane currents. Furthermore, the application of nimodipine, an L-Type calcium ion channel blocker, ryanodine, a ryanodine receptor modifier, and heparin, an IP3 receptor blocker, decreased the emodin-induced BK channel currents, respectively. BAPTA-AM, a selective calcium ion chelator, abolished the emodin-induced BK channel currents. Emodin repolarized cytomembrane and enhanced BK channel open probabilities and elevated cytosolic calcium ion concentration. CONCLUSION: The vasorelaxant effect of emodin on vessels is mediated through the activation of BK channels.


Assuntos
Emodina , Canais de Potássio Ativados por Cálcio de Condutância Alta , Animais , Cálcio/metabolismo , Emodina/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/farmacologia , Músculo Liso Vascular , Miócitos de Músculo Liso/metabolismo , Técnicas de Patch-Clamp , Ratos , Artéria Renal/metabolismo
13.
Phytomedicine ; 106: 154403, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36075180

RESUMO

BACKGROUND: Previous studies reported that Aloe vera ameliorated DSS-induced colitis and promoted mucus secretion. However, the effect of Aloin A (AA), a major compound of Aloe vera, on colitis and its exact mechanism remains uncovered. METHODS: C57BL/6 mice were successively subjected to 3% DSS solution for 5 days and distilled water for 2 days. Concurrently, AA (25, 50 mg/kg) and 5-aminosalicylic (500 mg/kg) were administrated intragastrically from day 1 to day 7. Colitis was evaluated by disease active index (DAI), colon length, inflammation response, and intestinal barrier function. In vitro LS174T cells challenged with 50 ng/ml of lipopolysaccharides (LPS) were used to validate the modulatory action of AA on the Notch signaling pathway. RESULTS: Our results showed that oral administration with AA prominently prevented DSS-induced colitis symptoms in terms of decreased DAI, prevention of colon shortening, and reduced pathological damage. AA mitigated the inflammatory response evidenced by the decreased proinflammatory cytokines (TNF-α, IL-1ß, IL-6) and increased anti-inflammatory cytokine (IL-10). Besides, AA inhibited apoptosis and facilitated proliferation in colons. Moreover, AA treatment up-regulated the expression of tight junction (TJ) proteins (ZO-1, Occludin) and promoted the secretion of MUC2 to decrease colon permeability. Mechanistically, AA inhibited the Notch pathway to promote the secretion of MUC2, which was consistent with LPS-challenged LS174 cells. CONCLUSION: These results suggested that AA could prevent colitis by enhancing the intestinal barrier function via suppressing the Notch signaling pathway. Thus, AA might be a prospective remedy for ulcerative colitis.


Assuntos
Colite Ulcerativa , Colite , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/prevenção & controle , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/prevenção & controle , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Emodina/análogos & derivados , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Estudos Prospectivos , Transdução de Sinais , Proteínas de Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Água
14.
Sci Rep ; 12(1): 16247, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171401

RESUMO

Cholangiocarcinoma (CCA) is a highly malignant disease with a poor prognosis, and mechanisms of initiation and development are not well characterized. It is long noncoding RNAs (lncRNAs) acting as miRNA decoys to regulate cancer-related RNAs in competing endogenous RNA (ceRNA) networks that suggest a possible molecular mechanism in CCA. The current study aims to find potential prognosis biomarkers and small molecule therapeutic targets based on the construction of a CCA prognosis-related ceRNA network. A transcriptome dataset for CCA was downloaded from the TCGA database. Differentially expressed lncRNAs (DElncRNAs), DEmiRNAs and DEmRNAs were identified based on the differential expression and a DEceRNA network was constructed using predicted miRNA-lncRNA and miRNA-mRNA interactions. Heat maps, PCA analysis, and Pathway enrichment analysis and GO enrichment analysis were conducted. The prognostic risk model and molecular docking were constructed based on identified key ceRNA networks. A DElncRNA-miRNA-mRNAs network consisting of 434 lncRNA-miRNA pairs and 284 miRNA-mRNA pairs with 200 lncRNAs, 21 miRNAs, and 245 mRNAs was constructed. There were three lncRNAs (AC090772.1, LINC00519, and THAP7-AS1) and their downstream mRNAs (MECOM, MBNL3, RCN2) screened out as prognostic factors in CAA. Three key networks (LINC00519/ hsa-mir-22/ MECOM, THAP7-AS1/hsa-mir-155/MBNL3, and THAP7-AS1/hsa-mir-155/RCN2) were identified based on binding sites prediction and survival analysis. A prognostic risk model was established with a good predictive ability (AUC = 0.66-0.83). Four anticancer small molecules, MECOM and 17-alpha-estradiol (-7.1 kcal/mol), RCN2 and emodin (-8.3 kcal/mol), RCN2 and alpha-tocopherol (-5.6 kcal/mol), and MBNL3 and 17-beta-estradiol (-7.1 kcal/mol) were identified. Based on the DEceRNA network and Kaplan-Meier survival analysis, we identified three important ceRNA networks associated with the poor prognosis of CCA. Four anti-cancer small molecules were screened out by computer-assisted drug screening as potential small molecules for the treatment of CCA. This study provides theoretical support for the development of ceRNA network-based drugs to improve the prognosis of CCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Emodina , MicroRNAs , RNA Longo não Codificante , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio , Colangiocarcinoma/patologia , Biologia Computacional , Estradiol , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Simulação de Acoplamento Molecular , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA , alfa-Tocoferol
15.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4148-4155, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046905

RESUMO

This study aimed to explore the efficacy and mechanism of combined rhein and emodin in the treatment of ulcerative colitis(UC) from the aspects of network pharmacology, animal inflammation improvement and molecular mechanism. Network pharmacology predicted that combined rhein and emodin acted on 52 potential targets, mainly participating in signaling pathways such as cancer, PI3 K/AKT, microRNAs in cancer and apoptosis. PI3 K/AKT signaling pathway has been reported to be closely related to UC, and the optimal candidate pathway for combined therapy. The UC mice model was established by dextran sodium sulfate, and then the modeled mice were randomly divided into control group, model group, rhein group, emodin group, rhein+emodin group and sulfasalazine group. After administration, compared with the conditions in model group, body weight, disease activity index(DAI) score, colon length, TNF-α, IL-6, IL-1ß and myeloperoxidase(MPO) of mice in rhein+emodin group were improved(P<0.01); colonic mucosal injury was significantly reduced; the expression of p-PI3 K/PI3 K and p-AKT/AKT proteins were down-regulated(P<0.01). All the above indices were better than those in the rhein/emodin group alone. The Jin's Q-values of the effect of combined rhein and emodin on colon length, TNF-α, IL-6, IL-1ß, MPO, p-PI3 K/PI3 K and p-AKT/AKT were all greater than 1.15, which indicated that there was obvious synergistic effect between rhein and emodin. In all, rhein and emodin have synergistic effect in the treatment of UC, and the mechanism may be related to the inhibition of PI3 K/AKT signaling pathway and the down-regulation of proinflammatory factors. They are the new components in the treatment of UC, which is worthy of attention.


Assuntos
Colite Ulcerativa , Emodina , Rheum , Animais , Antraquinonas , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo , Modelos Animais de Doenças , Emodina/farmacologia , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4214-4220, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046912

RESUMO

This study aims to establish an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method for the determination of emodin-8-O-ß-D-glucoside(EG) and its metabolites in plasma, and to investigate the toxicokinetics(TK) behavior of them in rats. To be specific, the TK of EG and its metabolites from the first to the last administration in the repeated dose toxicity study was determined, and the kinetic parameters were calculated. The exposure of EG prototype and metabolites in rat plasma after oral administration of different doses of EG was evaluated. The result showed that the prototype of EG and its metabolites aloe-emodin-8-O-ß-D-glucoside, emodin, aloe-emodin, and hydroxyemodin could be detected in rats after oral administration of high-, medium-, and low-dose EG. The area under the curve(AUC) of the prototype and metabolites after the first and last administration was in positive correlation with the dose. The time to the maximum concentration(T_(max)) of EG and metabolites in the three administration groups was <6 h, and the longest in vivo residence time was 12 h. The T_(max) and in vivo residence time of EG were prolonged with the increase in the dose. The metabolites emodin, aloe-emodin, and hydroxyemodin all had two peaks. Both hydroxyemodin and aloe-emodin exhibited increased plasma exposure, slow metabolism, and accumulation in vivo. In addition, aloe-emodin-8-O-ß-D-glucoside and emodin disappeared with the increase in dose, suggesting the change of the metabolic pathway of EG in vivo in the case of high-dose administration. The mechanism of high-dose EG in vivo needs to be further explored. This study preliminarily elucidates the TK behavior of EG in rats, which is expected to support clinical drug use.


Assuntos
Emodina , Animais , Antraquinonas , Cromatografia Líquida de Alta Pressão/métodos , Emodina/toxicidade , Glucosídeos/toxicidade , Espectrometria de Massas , Ratos , Toxicocinética
17.
Microbiol Spectr ; 10(5): e0054422, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36069576

RESUMO

Treatment of osteomyelitis is still challenging, as conventional antibiotic therapy is limited by the emergence of resistant strains and the formation of biofilms. Sonoantimicrobial chemotherapy (SACT) is a novel therapy of low-frequency and low-intensity ultrasound (LFLIU) combined with a sonosensitizer. Therefore, in our study, a sonosensitizer named emodin (EM) was proposed to be combined with LFLIU to relieve acute osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) through antibacterial and antibiofilm effects. The efficiencies of different intensities of ultrasound, including single (S-LFLIU, 15 min) and multiple ultrasound (M-LFLIU, 3 times for 5 min at 4-h intervals), against bacteria and biofilms were compared, contributing to developing the best treatment regimen. Our results demonstrated that EM plus S-LFLIU or M-LFLIU (EM+S-LFLIU or EM+M-LFLIU) had significant combined bactericidal and antibiofilm effects, with EM+M-LFLIU in particular exhibiting superior antibiofilm performance. Furthermore, it was suggested that EM+M-LFLIU could produce a large amount of reactive oxygen species (ROS), destroy the integrity of the bacterial membrane and cell wall, and downregulate the expression of genes involved in oxidative stress, membrane wall synthesis, and bacterial virulence, as well as that of other related genes (agrB, pbp3, sgtB, gmk, zwf, and msrA). In vivo studies, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and bacterial quantification of bone tissue indicated that EM+M-LFLIU could also relieve osteomyelitis due to MRSA infection. Our work proffers an original approach to bacterial osteomyelitis treatment that weakens drug-resistant bacteria and suppresses and degrades biofilm formation through SACT, which may provide new prospects for clinical treatment. IMPORTANCE Antibiotic therapy is the first choice for clinical treatment of osteomyelitis, but the formation of bacterial biofilms and the emergence of many drug-resistant strains also create an urgent need to find an alternative treatment to effectively eliminate the infection. Recently, LFLIU has come to be considered a safe and promising method of debridement and antibacterial therapy. In this study, we found that ultrasound and EM have a significant combined antibacterial effect in vivo and in vitro, which may play an antibacterial role by stimulating the production of ROS, destroying the bacterial cell wall, and inhibiting the expression of related genes. Our study expands the body of knowledge on the antibacterial effect of drugs-specifically emodin (EM)-through combined physiotherapy. If successfully integrated into clinical practice, these methods may reduce the burden of high concentrations of drugs needed to treat bacterial biofilms and avoid the growing resistance of bacteria to antibiotics.


Assuntos
Emodina , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Emodina/farmacologia , Emodina/uso terapêutico , Espécies Reativas de Oxigênio/farmacologia , Espécies Reativas de Oxigênio/uso terapêutico , Testes de Sensibilidade Microbiana , Microtomografia por Raio-X , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Osteomielite/diagnóstico por imagem , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
18.
Bioorg Med Chem Lett ; 75: 128974, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36064125

RESUMO

Emodin (EM) is one of the active components of the traditional Chinese medicine rhubarb, and there is evidence of its hypolipidemic activity, though the exact mechanism is unknown. NPC1L1 is a key protein in human cholesterol uptake that is primarily expressed in hepatocytes and gastrointestinal epithelial cells. Our findings suggest that rhodopsin inhibits cellular cholesterol uptake by influencing NPC1L1 cholesterol transport. The results showed that NBD-cholesterol uptake in human HepG2 cells was 27 %, 31.3 %, 33.6 %, 41.6 %, and 52.6 % of control after treatment with 100, 75, 50, 25, and 12.5 % M EM, respectively, compared to 50 % for 100 M Ezetimibe. Kinetic studies revealed that EM inhibited cellular uptake of cholesterol through anti-competitive inhibition. Furthermore, using confocal fluorescence quantification, we discovered that after cholesterol deprivation treatment reintroduced cholesterol supply, cholesterol uptake was significantly higher in HepG2 cells highly expressing NPC1L1 than in U2OS cells with low NPC1L1 expression. As a result, we hypothesize that EM may inhibit cholesterol uptake via NPC1L1 in human hepatocytes in an anti-competitive manner. Overall, as a dietary supplement or lipid-modifying drug, EM has the potential to lower cholesterol.


Assuntos
Emodina , Colesterol/metabolismo , Emodina/farmacologia , Ezetimiba/farmacologia , Humanos , Cinética , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Rodopsina/metabolismo
19.
Phytomedicine ; 107: 154449, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36126406

RESUMO

BACKGROUND: Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of commercial whitening agents in managing skin melanin such as kojic acid and arbutin can lead to some negative effects such as dermatitis and liver cancer. Although past studies have researched the melanin inhibitory effect of plant extracts, the effective dose and mechanisms are not well summarized and discussed. This study aims to explore the melanin inhibitory property of phytochemicals and tries to answer the following research questions: (1) Which plant extracts and phytochemicals could inhibit melanin biosynthesis in the skin? what is the mechanism of action? (2) Have human trials been conducted to confirm their melanin inhibitory effect? (3) If not, which phytochemicals are recommended for further human trials? This article would provide information for future research to develop natural and safe skin whitening products. METHODS: A preferred reporting items for systematic reviews and meta-analyses (PRISMA) systematic review method and OHAT risk-of-bias tool were applied to screen literature from 2000 to 2021 and 50 research articles met the selection criteria. RESULTS: Flavonoids, phenolic acids, stilbenes and terpenes are main classes of phytochemicals responsible for the melanin inhibitory effects. The in vitro/in vivo melanin inhibitory effects of these plant extracts/phytochemicals are achieved via three main mechanisms: (1) the ethyl acetate extract of Oryza sativa Indica cv., and phytochemicals such as galangin and origanoside could manage melanin biosynthesis through competitive inhibition, non-competitive inhibition or mixed-type inhibition of tyrosinase; (2) phytochemicals such as ginsenoside F1, ginsenoside Rb1 and 4­hydroxy-3-methoxycinnamaldehyde could inhibit melanogenesis through down-regulating microphthalmia-related transcription factor (MITF) gene expression via different signalling pathways; (3) the ethanolic extracts of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius have a good ultraviolet absorption ability and high sun protective factor (SPF) values, thereby inhibiting UV induced melanogenesis in the skin. CONCLUSION: Although many plant extracts and phytochemicals have been found to inhibit melanin production, most of the results were only proved in cellular and/or animal models. Only the ethyl acetate extract of Oryza sativa Indica cv. panicle, and ginsenoside F1 were proved effective in human trials. Animal studies proved the effectiveness of galangin, origanoside, ginsenoside Rb1 and 4­hydroxy-3-methoxycinnamaldehyde with effective dose below 3 mM, and therefore recommended for future human trial. In addition, cellular studies have demonstrated the effectiveness of oxyresveratrol, mulberroside A, kurarinol, kuraridinol, plumbagin, (6aR,11aR)-3,8-dihydroxy-9­methoxy pterocarpan, ginsenoside Rh4, cardamonin, nobiletin, curcumin, ß-mangostin and emodin in inhibiting melanin synthesis at low concentrations of 20 µM and proved the low SPF values of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius extracts, and therefore recommended for further animal and human trials.


Assuntos
Clareadores , Curcumina , Emodina , Pterocarpanos , Estilbenos , Acetatos , Acroleína/análogos & derivados , Animais , Arbutina/farmacologia , Linhagem Celular Tumoral , Flavonoides/farmacologia , Ginsenosídeos , Glucosídeos , Humanos , Hidroxibenzoatos , Melaninas , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fatores de Transcrição
20.
J Pharm Sci ; 111(12): 3232-3242, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35995206

RESUMO

The aim of the present study was to explore the antileishmanial performance and wound healing effect of exosomes isolated from Wharton Jelly derived mesenchymal stem cells (WJ-MSCs) in combination with aloe-emodin. MSCs obtained from Wharton Jelly were characterized by flow cytometry. Exosomes were isolated from cultivated stem cells by ultacentrifugation method. Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and flow cytometry were used for characterization of obtained exosomes. The cytotoxicities of characterized exosomes and aloe-emodin at different concentrations were investigated on L929 and J774 cell lines. Non-toxic concentrations of each agent were combined and their inhibitory efficacies on L.major promastigotes and amastigotes were investigated by different techniques such as MTT, parasite count and measurements of infection index. Finally, wound healing activities of combinations were examined on in vitro artifical wound model and compared with the use of exosomes alone. According to outcome of flow cytometic analysis, vesicles isolated from WJ-MSCs highly expressed the markers such as CD63 special for exosome profile. SEM and NTA results demonstrated that derived exosomes possessed dimensions between 150 to 200 nanometers and elicited the cup-shape specific to exosomes. Combinations including non-toxic dosages of exosomes and aloe-emodin demonstrated superior antileishmanial effectivenesses both on promastigotes and amastigotes in contrast to use of exosome alone since they lead to inhibition of promastigotes and amastigotes for 4 and 10-folds in comparison to control, respectively. Additionally, combinations elicited more rapidly and effective in vitro wound-healing performance in contrast to use of exosome alone. At the end of 24 h incubation application of combinations gave rise to wound closure at a rate of 72 %, while in the control group 52 % of wound area has not been healed, yet. These results reflect that mentioned combination has great potential to be used in treatment of cutaneus leishmaniasis (CL) since they have magnificient capacity to inhibit Leishmania parasites while enhancing wound healing.


Assuntos
Aloe , Emodina , Exossomos , Células-Tronco Mesenquimais , Geleia de Wharton , Cicatrização
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...