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1.
Fish Shellfish Immunol ; 94: 842-851, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31585245

RESUMO

Dietary lipids and fatty acids are involved in cell metabolism and animal physiological regulation. However, oxidized lipids could induce oxidative stress and disorder normal growth and physiological health in fish. A 12-week rearing experiment with 6% fish oil (6F), 6% oxidized fish oil (6OF) and emodin supplemented diets (6F + E, 6OF + E) was conducted to evaluate the protective mechanism of emodin on oxidized fish oil stress in Megalobrama amblycephala. Results indicate that, under oxidized fish oil stress, emodin rescued the growth performance inhibition, improved special growth ratio (SGR), and reduced feed conversion ratio (FCR) and hepatosomatic index (HSI); rescued intestine histological impairment, ameliorated the structural expansion and membrane damage of mitochondria in intestine cells, and increased the length and intensity of intestinal villus. Moreover, emodin enhanced serum immune and antioxidant enzyme activity, increased metabolic activity through PPARs signaling, increased antioxidant capacity through PPARs and Nrf2-Keap1 signaling based on the transcriptional expression of specific genes. These results indicate emodin could be used as an effective immunostimulant to protect organism form oxidative stress induced by dietary oxidized lipid. This may provide insights for oxidized lipid prevention in aquaculture production.


Assuntos
Cyprinidae/imunologia , Emodina/farmacologia , Óleos de Peixe/efeitos adversos , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/imunologia , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Cyprinidae/genética , Cyprinidae/crescimento & desenvolvimento , Cyprinidae/metabolismo , Dieta/efeitos adversos , Dieta/veterinária , Gorduras Insaturadas na Dieta/efeitos adversos , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Emodina/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Estresse Oxidativo , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos
2.
Artif Cells Nanomed Biotechnol ; 47(1): 3961-3975, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31588802

RESUMO

Ion-complementary self-assembling peptides have potential in delivering hydrophobic drugs. This study involved two self-assembling peptides, RADA16-I and RVDV16-I, of which RVDV16-I was a novel self-assembling peptide with different hydrophobic side chains designed from RADA16-I. The purpose of this study was to observe the interaction between different self-assembling peptides and emodin through fluorescence spectrophotometry, CD, SEM and AFM; to construct a preliminary suspension in-situ hydrogel delivery system for emodin with the self-assembling peptides; and to investigate the drug-loading and drug-releasing properties of the self-assembling peptides on emodin. The results showed that both peptides can interact with emodin and the interaction was dominated by hydrophobic interaction. The aqueous solutions of both self-assembling peptides can form relatively stable suspensions with emodin under mechanical stirring, and the suspension can form in-situ hydrogel under physiological condition. In vitro release of emodin from the hydrogels showed a manner of sustained release to some extent. Cell viability studies showed inherent proliferation inhibiting effects of emodin on tumor cells was maintained or enhanced through the in-situ hydrogels. The self-assembling peptides RADA16-I and RVDV16-I had showed promising drug-loading and drug-releasing performance for hydrophobic drugs. It is reasonable to exploit self-assembling peptides as drug carriers for their great potential to improve delivery of hydrophobic drugs.


Assuntos
Antineoplásicos/química , Preparações de Ação Retardada/química , Emodina/química , Hidrogéis/química , Peptídeos/química , Células A549 , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emodina/administração & dosagem , Emodina/farmacologia , Células Hep G2 , Humanos , Hidrogéis/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Suspensões
3.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 32-37, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304903

RESUMO

To investigate the effects of emodin on learning and memory and protein kinase C (PKC) signaling pathway in Alzheimer's disease (AD) model mice. 60 APP/PS1 double transgenic AD mice were selected as model mice at the age of 7-8 months, 36 healthy male C57BL/6 mice served as the control group. Morris water maze method and passive avoidance experiment were used to evaluate the memory ability of mice. The thiazole blue (MTT) method and the lactate dehydrogenase (LDH) cytotoxicity test kit were used to evaluate the effect of emodin on the cell viability of hippocampal neurons in HT22 mice treated with ß-amyloid peptide 1-42 (Aß1-42). The effect of emodin on PKC levels was explored using the modified Takai method and Western blotting. Behavioral test results showed that the escape latency of the mice in the model group was longer than that in the control group (P<0.05), and the escape latency was significantly shortened given a emodin prognosis. The MTT and LDH test results showed that emodin to Aß- overexpression induced the protective effect of hippocampus cells in HT22 mice. Western blot analysis showed that the phosphorylation level of PKC in mice increased significantly after emodin administration. Emodin can attenuate oxidative stress and inflammatory response in Alzheimer's model mice by activating PKC pathway, thereby improving cognitive function.


Assuntos
Doença de Alzheimer/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Emodina/farmacologia , Substâncias Protetoras/farmacologia , Proteína Quinase C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Emodina/administração & dosagem , Emodina/uso terapêutico , Hipocampo/patologia , Inflamação/metabolismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Fosforilação/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico
4.
Mater Sci Eng C Mater Biol Appl ; 103: 109813, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349435

RESUMO

A γ-irradiated bovine albumin serum-based nanoparticle was characterised structurally, and functionally. The nanoparticle was characterised by A.F.M., D.L.S, zeta potential, T.E.M., gel-electrophoresis, and spectroscopy. We studied the stability of the nanoparticle at different pH values and against time, by fluorescence spectroscopy following the changes in the tryptophan environment in the nanoparticle. The nanoparticle was also functionalized with Folic Acid, its function as a nanovehicle was evaluated through its interaction with the hydrophobic drug Emodin. The binding and kinetic properties of the obtained complex were evaluated by biophysical methods as well as its toxicity in tumor cells. According to its biophysics, the nanoparticle is a spherical nanosized vehicle with a hydrodynamic diameter of 70 nm. Data obtained describe the nanoparticle as nontoxic for cancer cell lines. When combined with Emodin, the nanoparticle proved to be more active on MCF-7 cancer cell lines than the nanoparticle without Emodin. Significantly, the albumin aggregate preserves the main activity-function of albumin and improved characteristics as an excellent carrier of molecules. More than carrier properties, the nanoparticle alone induced an immune response in macrophages which may be advantageous in vaccine and cancer therapy formulation.


Assuntos
Portadores de Fármacos/química , Emodina/administração & dosagem , Nanopartículas/química , Soroalbumina Bovina/química , Animais , Sistemas de Liberação de Medicamentos , Emodina/farmacologia , Ácido Fólico/química , Raios gama , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , NF-kappa B/metabolismo , Nanopartículas/toxicidade , Soroalbumina Bovina/farmacologia , Soroalbumina Bovina/toxicidade , Espectrometria de Fluorescência
5.
J Sep Sci ; 42(14): 2341-2350, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037812

RESUMO

In China, Semen Cassiae has long been used to protect liver, brighten eyes, and relieve constipation. Prepared Semen Cassiae is produced from raw Semen Cassiae by processing, the two forms of Semen Cassiae have different clinical applications. Pathological state is an important factor affecting the efficacy of drugs, the pharmacokinetic behavior of drugs could be significantly changed when people or animal were under different pathological state. To clarify the effect of processing mechanism and pathological state for pharmacokinetic behavior, the pharmacokinetics of nine components of raw and prepared Semen Cassiae under normal and acute liver injury rats were examined. The results showed that the bimodal phenomenon appeared on the plasma concentration-time profiles of obtusin, emodin, chrysophanol, aloe emodin and rhein. The Tmax of aurantio-obtusin, obtusin, chrysoobtusin, emodin, chrysophanol, aloe emodin, physcion in normal groups administrated prepared Semen Cassiae were shorter than those administrated raw Semen Cassiae. For the AUC0-t , aurantio-obtusin, obtusin, chrysoobtusin, chrysophanol, aloe emodin and physcione in model groups administrated prepared Semen Cassiae were significantly higher than other groups, unlike above components, rhein had poor absorption in model groups. The study would be useful for further studies on pharmacokinetics and clinical application of raw and prepared Semen Cassiae.


Assuntos
Cassia/química , Doença Hepática Induzida por Substâncias e Drogas/sangue , Medicamentos de Ervas Chinesas/farmacocinética , Administração Oral , Animais , Antraquinonas/administração & dosagem , Antraquinonas/sangue , Antraquinonas/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Emodina/administração & dosagem , Emodina/análogos & derivados , Emodina/sangue , Emodina/farmacocinética , Masculino , Ratos , Ratos Sprague-Dawley
6.
Molecules ; 24(10)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108858

RESUMO

(1) Background: Rhubarb anthraquinones-a class of components with neuroprotective function-can be used to alleviate cerebral ischemia reperfusion injury. (2) Methods: The three pharmacodynamic indicators are neurological function score, brain water content, and cerebral infarction area; UPLC-MS/MS was used in pharmacokinetic studies to detect plasma concentrations at different time points, and DAS software was used to calculate pharmacokinetic parameters in a noncompartmental model. (3) Results: The results showed that the pharmacodynamics and pharmacokinetics of one of the five anthraquinone aglycones could be modified by the other four anthraquinones, and the degree of interaction between different anthraquinones was different. The chrysophanol group showed the greatest reduction in pharmacodynamic indicators comparing with other four groups where the rats were administered one of the five anthraquinones, and there was no significant difference between the nimodipine group. While the Aloe-emodin + Physcion group showed the most obvious anti-ischemic effect among the groups where the subjects were administered two of the five anthraquinones simultaneously. Emodin, rhein, chrysophanol, and physcion all increase plasma exposure levels of aloe-emodin, while aloe-emodin lower their plasma exposure levels. (4) Conclusions: This experiment provides a certain preclinical basis for the study of anthraquinone aglycones against cerebral ischemia and a theoretical basis for the study of the mechanism of interaction between anthraquinones.


Assuntos
Antraquinonas/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Rheum/química , Aloe/química , Animais , Antraquinonas/química , Antraquinonas/farmacocinética , Modelos Animais de Doenças , Quimioterapia Combinada , Emodina/administração & dosagem , Emodina/análogos & derivados , Emodina/química , Emodina/farmacocinética , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Ratos
7.
Am J Chin Med ; 47(3): 613-633, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30966773

RESUMO

High mobility group box 1 (HMGB1) is recognized as a late mediator of sepsis, and the inhibition of HMGB1 release and recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis. We tested the hypothesis that aloin induces sirtuin 1 (SIRT1) and heme oxygenase (HO)-1, which inhibit HMGB1 release in lipopolysaccharide (LPS)-stimulated cells, thereby inhibiting HMGB1-induced hyperpermeability and increasing the survival of septic mice. Aloin was administered after LPS or HMGB1 challenge, and the antiseptic activity of aloin was determined from measurements of permeability, activation of pro-inflammatory proteins and production of markers for tissue injury in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and a cecal ligation and puncture (CLP)-induced sepsis mouse model. Aloin significantly reduced HMGB1 release in LPS-activated HUVECs via SIRT1-mediated HMGB1 deacetylation and the PI3K/Nrf2/heme oxygenase (HO)-1 signaling axis. Aloin also suppressed the production of tumor necrosis factor (TNF)- α and interleukin (IL)-6, as well as the activation of nuclear factor (NF)- κ B and extracellular signal-regulated kinase 1/2 (ERK 1/2) by HMGB1. Moreover, aloin restored HMGB1-mediated vascular disruption and inhibited vascular hyperpermeability in mice. In addition, treatment with aloin reduced the CLP-induced release of HMGB1, sepsis-related mortality and tissue injury in vivo. Our results suggest that aloin reduces HMGB1 release and sepsis-related mortality by activating SIRT1 and PI3K/Nrf2/HO-1 signals, indicating that aloin has potential for the treatment of sepsis.


Assuntos
Emodina/análogos & derivados , Proteína HMGB1/metabolismo , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Sepse/tratamento farmacológico , Sepse/etiologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Aloe/química , Animais , Modelos Animais de Doenças , Emodina/administração & dosagem , Emodina/farmacologia , Proteína HMGB1/antagonistas & inibidores , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fitoterapia , Sepse/genética , Sepse/metabolismo
8.
Food Chem Toxicol ; 126: 67-71, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30769049

RESUMO

Aloin is the major anthraquinone glycoside obtained from the Aloe species and exhibits anti-inflammatory and anti-oxidative activities. Here, we aimed to determine the effects of aloin on heme oxygenase-1 (HO-1) induction and on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX) 2 in lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs). To the end, aloin was tested whether aloin reduces iNOS protein expression and inflammatory markers (interleukin (IL)-1ß and tumor necrosis factor (TNF)-α) in LPS-treated mice lung tissue. The results indicated that aloin affected HO-1 induction and reduced LPS-activated NF-κB-luciferase activity showed to preferential inhibition of iNOS/NO and COX-2/PGE2 that was partly related to inhibition of STAT-1 phosphorylation. In particular, aloin induced translocation of Nrf2 from cytosol into the nucleus by an increased Nrf2-ARE binding activity, and reduced IL-1ß production in LPS-activated HUVECs. The reduced expression of iNOS/NO by aloin was reversed by siHO-1RNA-transfection. In LPS-treated mice, aloin significantly reduced iNOS protein in lung tissues, and TNF-α levels in the BALF. We concluded that aloin may be beneficial for treatment of lung injury.


Assuntos
Anti-Inflamatórios/administração & dosagem , Emodina/análogos & derivados , Pneumopatias/tratamento farmacológico , NF-kappa B/imunologia , Óxido Nítrico Sintase Tipo II/genética , Extratos Vegetais/administração & dosagem , Fator de Transcrição STAT1/imunologia , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Emodina/administração & dosagem , Heme Oxigenase-1/genética , Heme Oxigenase-1/imunologia , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/imunologia , Humanos , Pneumopatias/genética , Pneumopatias/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Óxido Nítrico Sintase Tipo II/imunologia , Fator de Transcrição STAT1/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
9.
J Pharm Biomed Anal ; 164: 672-680, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30472586

RESUMO

Polygoni Multiflori Radix (PMR) has been a reputable tonifying traditional Chinese medicine for a long history. However, clinical side effects regarding its idiosyncratic hepatotoxicity are occasionally reported. The containing anthraquinones, particularly emodin, could cause liver injury in both in vitro and in vivo experiments. It is well-known that some compounds could influence other compounds' pharmacokinetic parameters significantly. In this work, the influence of trans-2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucopyranoside (TSG) on the pharmacokinetic behavior of emodin in rats was evaluated by an ultra-high performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC/MS-MS) approach. Pharmacokinetic parameters of emodin, PMR extract, and TSG-free PMR extract (prepared by a component "knock-out" strategy with TSG eliminated), in rats after one-day and seven-day administration were determined and compared. We found that, after seven-day administration of the whole PMR extract (rather than TSG-free extract), emodin in rats was accumulated. And accordingly, the exposure of emodin in rats pre-treated with single TSG for seven days could be significantly enhanced. The results indicate that TSG was able to accelerate the exposure and metabolism of emodin. The effect of TSG on the metabolic activities of cytochrome P450 enzymes was further assessed by an LC-MS cocktail method. The accelerated exposure and metabolism of emodin could result from the up-regulation activity of CYP450s, in particular CYP1A2 isozyme. The findings obtained in this work firstly unveiled DDI between TSG and emodin in the administration of PMR, thus may provide a basis for unveiling the underlying mechanism of PMR-induced liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/farmacocinética , Emodina/farmacocinética , Glucosídeos/farmacocinética , Polygonum/química , Estilbenos/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Citocromo P-450 CYP1A2/metabolismo , Modelos Animais de Doenças , Interações Medicamentosas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Emodina/administração & dosagem , Emodina/toxicidade , Glucosídeos/administração & dosagem , Glucosídeos/toxicidade , Humanos , Masculino , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Estilbenos/administração & dosagem , Estilbenos/toxicidade , Espectrometria de Massas em Tandem/métodos
10.
Int J Mol Sci ; 19(10)2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30321984

RESUMO

Reduced therapeutic efficacy of sorafenib, a first-generation multikinase inhibitor, is often observed during the treatment of advanced hepatocellular carcinoma (HCC). Emodin is an active component of Chinese herbs, and is effective against leukemia, lung cancer, colon cancer, pancreatic cancer, and HCC; however, the sensitizing effect of emodin on sorafenib-based HCC therapy has not been evaluated. Here, we demonstrate that emodin significantly improved the anti-cancer effect of sorafenib in HCC cells, such as HepG2, Hep3B, Huh7, SK-HEP-1, and PLC/PRF5. Mechanistically, emodin inhibits sterol regulatory element-binding protein-2 (SREBP-2) transcriptional activity, which suppresses cholesterol biosynthesis and oncogenic protein kinase B (AKT) signaling. Additionally, attenuated cholesterol synthesis and oncogenic AKT signaling inactivated signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. Furthermore, emodin synergistically increased cell cycle arrest in the G1 phase and apoptotic cells in the presence of sorafenib. Animal models xenografted with HepG2 or SK-HEP-1 cells also showed that the combination of emodin and sorafenib was sufficient to inhibit tumor growth. Overall, these results suggested that the combination of emodin and sorafenib may offer a potential therapy for patients with advanced HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Colesterol/metabolismo , Emodina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/administração & dosagem , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Emodina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Sorafenibe/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Drug Des Devel Ther ; 12: 2195-2211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034224

RESUMO

Background: Endoplasmic reticulum stress is associated with podocyte apoptosis in the pathogenesis of diabetic nephropathy (DN). A previous study has demonstrated that emodin has a protective effect in the kidney by suppressing proliferation of mesangial cells and inhibiting the renal tubular epithelial-to-mesenchymal transition. However, the effects of emodin on the podocyte apoptosis in DN and its mechanisms are unknown. Aim: This study aimed to explore the effect of emodin on DN model KK-Ay mice and high glucose induced podocytes apoptosis via the PERK-eIF2α pathway. Methods: KK-Ay mice model of DN were treated with emodin at dose of 40 and 80 mg/kg/day for 8 weeks. Urine albumin, serum creatinine, blood urea nitrogen levels and the renal histopathology in mice were performed. In vitro, conditionally immortalized mouse podocytes exposed to HG (30mM) were incubated with emodin. Cell viability was measured by CCK-8 assay. Additionally, we performed RNA interference and measured the apoptosis in cultured podocytes treated with emodin. Immunohistochemistry, immunofluorescence, western blot, and real-time PCR were used to detect gene and protein expression both in vivo and in vitro. Results: The results showed that emodin treatment ameliorated urine albumin, serum creatinine, and blood urea nitrogen of DN mice. The pathological damage of kidney tissue was also improved after treatment with emodin. Moreover, emodin increased nephrin expression. Podocytes apoptosis and endoplasmic reticulum stress markers (GRP78) were significantly reduced upon emodin treatment. Furthermore, emodin treatment decreased the expression of phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (P-PERK), phosphorylated P-eIF2α, ATF4, and CHOP. In vitro, emodin treatment was further found to decrease the GRP78 level induced by high glucose or tunicamycin (TM). Besides, emodin and PERK knockdown inhibited the apoptosis of podocytes cultured in high glucose by counteracting the upregulation of phosphorylated PERK, phosphorylated eIF2α, ATF4, and CHOP. Conclusion: Overall, the findings indicate that emodin mitigates podocytes apoptosis by inhibiting the PERK-eIF2α signaling pathway in vivo and in vitro, and, therefore, exerts a protective action on podocytes in DN.


Assuntos
Apoptose/efeitos dos fármacos , Nefropatias Diabéticas/tratamento farmacológico , Emodina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas Quinases/farmacologia , eIF-2 Quinase/antagonistas & inibidores , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Relação Dose-Resposta a Droga , Emodina/administração & dosagem , Emodina/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Podócitos/patologia , Proteínas Quinases/administração & dosagem , Proteínas Quinases/química , Relação Estrutura-Atividade , eIF-2 Quinase/metabolismo
12.
Fish Shellfish Immunol ; 73: 252-261, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29242133

RESUMO

Enhancement of immune system seems to be the most promising method of preventing fish diseases. Several herbal products have immunostimulant properties, and are environmental friendly, economical and can act against a broad spectrum of pathogens. Present study was designed with an aim to evaluate the role of aloin, extracted from a herb Aloe barbadensis, in the modulation of certain immune parameters in an Indian major carp, Labeo rohita. Fishes were divided into control, vehicle control and aloin treated groups. Experiments were conducted for 7 days and fishes from the three groups were analyzed at 2d, 4d, 6d and 8d. The results demonstrated that at different intervals, L. rohita administered with aloin showed a significant increase in the activity of enzymes - lysozyme, protease, carboxylesterase, alkaline phosphatase, acid phosphatase, catalase and peroxidase, and non-enzymatic factors hemagglutinin and alternate complement compared with that of the controls. Thus, it can be concluded that administration of aloin is beneficial in enhancing the immune response and hence it can be used as potent immunostimulant in aquaculture.


Assuntos
Adjuvantes Imunológicos/metabolismo , Carpas/imunologia , Emodina/análogos & derivados , Imunidade Inata/efeitos dos fármacos , Pele/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Animais , Emodina/administração & dosagem , Emodina/metabolismo , Injeções Intraperitoneais/veterinária , Muco/efeitos dos fármacos , Distribuição Aleatória , Pele/imunologia
13.
Molecules ; 22(10)2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-29057806

RESUMO

Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK MAPK and nuclear translocation of NF-κB p65. Emodin also activated the Nrf2 pathway, decreased ROS levels, increased GSH levelss and GSH/GSSG ratio, and upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection. Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin on IAV-induced activations of TLR4, p38/JNK, and NF-κB pathways and on IAV-induced production of IL-1ß, IL-6 and expression of IAV M2 protein. Emodin also dramatically increased the survival rate of mice, reduced lung edema, pulmonary viral titer and inflammatory cytokines, and improved lung histopathological changes. In conclusion, emodin can inhibit IAV replication and influenza viral pneumonia, at least in part, by activating Nrf2 signaling and inhibiting IAV-induced activations of the TLR4, p38/JNK MAPK and NF-κB pathways.


Assuntos
Emodina/administração & dosagem , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Pneumonia/tratamento farmacológico , Animais , Modelos Animais de Doenças , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Influenza Humana/complicações , Influenza Humana/genética , Influenza Humana/virologia , Camundongos , Fator 88 de Diferenciação Mieloide/genética , Fator 2 Relacionado a NF-E2/genética , Pneumonia/etiologia , Pneumonia/patologia , Pneumonia/virologia , RNA Interferente Pequeno/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/genética , Receptor 4 Toll-Like/genética , Fator de Transcrição RelA/genética , Replicação Viral/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/genética
14.
Mol Med Rep ; 16(5): 5759-5768, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901386

RESUMO

Aloin has the potential to be a novel anticancer agent in cancer therapies. However, the detailed anticancer effect of Aloin remains to be fully elucidated. The present study analyzed the p53­dependent mechanisms in response to Aloin treatment. Using the p53­proficient A549 cells, an Aloin­induced apoptotic cell model was established, which was used to evaluate the potential underlying molecular mechanisms. The results demonstrated that 200, 300 and 400 µM Aloin induced intrinsic cell apoptosis, which was further confirmed by disruption of the mitochondrial membrane potential, elevation of cytosolic Ca2+ levels, and activation of B­cell lymphoma 2 (Bcl­2) homologous antagonist killer, Bcl­2 X­associated protein, p53 upregulated modulator of apoptosis and phorbol­12­myristate­13­acetate­induced protein 1. Aloin­induced apoptosis was also accompanied by the induction of p53 phosphorylation on Serine (Ser)15, Threonine 18, Ser20 and Ser392; however, there were no significant differences in the expression of p53 and mouse double minute 2 homolog. Aloin­induced apoptosis was reactive oxygen species (ROS)­ and c­Jun/p38­dependent, as specific inhibitors for ROS, phosphorylated (p)­c­Jun and p­p38 may attenuate Aloin­induced A549 cell proliferating inhibition. In conclusion, these results suggested that Aloin may induce apoptosis in A549 cells via the ROS­mitogen activated protein kinase signaling pathway, with p53 phosphorylation. These results implicate Aloin as a potential therapeutic agent for the treatment of lung cancer.


Assuntos
Apoptose/efeitos dos fármacos , Emodina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Proteína Supressora de Tumor p53/genética , Células A549 , Animais , Proliferação de Células/efeitos dos fármacos , Emodina/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteínas de Neoplasias/genética , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Oxid Med Cell Longev ; 2017: 1740317, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28831292

RESUMO

BACKGROUND: Postoperative intra-abdominal adhesions are a major complication after abdominal surgery. Although various methods have been used to prevent and treat adhesions, the effects have not been satisfactory. Emodin, a naturally occurring anthraquinone derivative and an active ingredient in traditional Chinese herbs, exhibits a variety of pharmacological effects. In our study, we demonstrated the effect of emodin treatment on preventing postoperative adhesion formation. MATERIALS AND METHODS: A total of 48 rats were divided into six groups. Abdominal adhesions were created by abrasion of the cecum and its opposite abdominal wall. In the experimental groups, the rats were administered daily oral doses of emodin. On the seventh day after operation, the rats were euthanized, and blood and pathological specimens were collected. Abdominal adhesion formation was evaluated by necropsy, pathology, immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay analyses. RESULTS: Abdominal adhesions were markedly reduced by emodin treatment. Compared with the control group, collagen deposition was reduced and the peritoneal mesothelial completeness rate was higher in the emodin-treated groups. Emodin had anti-inflammatory effects, reduced oxidative stress, and promoted the movement of the intestinal tract (P < 0.05). CONCLUSION: Emodin significantly reduced intra-abdominal adhesion formation in a rat model.


Assuntos
Abdome/patologia , Emodina/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/tratamento farmacológico , Animais , Modelos Animais de Doenças , Emodina/administração & dosagem , Emodina/farmacologia , Ratos , Ratos Sprague-Dawley
16.
Purinergic Signal ; 13(4): 559-568, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28840511

RESUMO

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). More than 90% of all cases of DM belong to type 2 diabetes mellitus (T2DM). Emodin is the main active component of Radix et rhizoma rhei and has anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects. Nanoparticle encapsulation of drugs is beneficial for drug targeting and bioavailability as well as for lowering drug toxicity side effects. The aim of this study was to investigate the effects of nanoparticle-encapsulated emodin (nano emodin) on diabetic neuropathic pain (DNP) mediated by the Purin 2X3 (P2X3) receptor in the dorsal root ganglia (DRG). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with nano emodin were higher compared with those in T2DM rats. Expression levels of P2X3 protein and messenger RNA (mRNA) in the DRG of T2DM rats were higher than those of controls, while levels in T2DM rats treated with nano emodin were significantly lower than those of the T2DM rats. Phosphorylation and activation of ERK1/2 in the T2DM DRG were decreased by nano emodin treatment. Nano emodin significantly inhibited currents activated by the P2X3 agonist α,ß-meATP in HEK293 cells transfected with the P2X3 receptor. Therefore, nano emodin treatment may relieve DNP by decreasing excitatory transmission mediated by the DRG P2X3 receptor in T2DM rats.


Assuntos
Neuropatias Diabéticas/metabolismo , Emodina/administração & dosagem , Gânglios Espinais/efeitos dos fármacos , Nanoconjugados , Receptores Purinérgicos P2X3/metabolismo , Animais , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Gânglios Espinais/metabolismo , Células HEK293 , Humanos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
17.
Chin J Nat Med ; 15(7): 534-539, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28807227

RESUMO

The present study was designed to investigate the anti-sepsis effects of physcion 8-O-ß-glucopyranoside (POG) isolated from Rumex japonicas and explore its possible pharmacological mechanisms. POG was extracted from R. japonicas by bioactivity-guided isolation with the anti-sepsis agents. Survival analysis in septic mouse induced by LPS and heat-killed Escherichia coli were used to evaluate the protective effect of POG (40 mg·kg-1, i.p.) on sepsis. Cytokines including TNF-α, IL-1ß and IL-6 in RAW 264.7 cells induced by LPS (100 ng·mL-1) were determined by ELISA. In addition, the proteins expressions of TLR2 and TLR4 were determined by Western blotting assay. Our results demonstrated that POG (40 mg·kg-1, i.p.) possessed significant protective activity on the endotoxemic mice. The POG treatment (20, 40, and 80 µg·mL-1) significantly decreased the TNF-α, IL-1ß and IL-6 induced by LPS (P < 0.01) in a concentration-dependent manner. Furthermore, the TLR4 and TLR2 proteins were also down-regulated by POG at 20 (P < 0.01), 40 (P < 0.01), and 80 µg·mL-1 (P < 0.01). The present study demonstrated that the POG extracted from R. japonicas possessed significant anti-sepsis effect on endotoxemic mice, and can be developed as a novel drug for treating sepsis in the future.


Assuntos
Anti-Inflamatórios/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Emodina/análogos & derivados , Glucosídeos/administração & dosagem , Rumex/química , Sepse/tratamento farmacológico , Animais , Emodina/administração & dosagem , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Células RAW 264.7 , Sepse/genética , Sepse/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
18.
Toxicol Sci ; 158(2): 302-318, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28525602

RESUMO

In a previous study, the oral administration of an Aloe vera whole leaf extract induced dose-related mucosal and goblet cell hyperplasia in the rat colon after 13 weeks and colon cancer after 2 years. The primary goal of this study was to determine whether or not the administration of aloin, a component of the Aloe vera plant leaf, would replicate the pathophysiological effects that were observed in rats in the previous study with an Aloe vera whole leaf extract. Groups of 10 male F344/N rats were administered aloin at 0, 6.95, 13.9, 27.8, 55.7, 111, 223, and 446 mg/kg drinking water for 13 weeks. At the end of study, rat feces were collected, and the composition of fecal bacteria was investigated by next generation sequencing of the PCR-amplified V3/V4 region of the 16S rRNA gene. At necropsy, blood was collected by cardiac puncture and organs and sections of the large intestine were collected for histopathology. Aloin induced dose-related increased incidences and severities of mucosal and goblet cell hyperplasia that extended from the cecum to the rectum, with increased incidences and severities detected at aloin doses ≥55.7 mg/kg drinking water. Analysis of the 16S rRNA metagenomics sequencing data revealed marked shifts in the structure of the gut microbiota in aloin-treated rats at each taxonomic rank. This study highlights the similarities in effects observed for aloin and the Aloe vera whole leaf extract, and points to a potential mechanism of action to explain the observed pathological changes via modulation of the gut microbiota composition.


Assuntos
Aloe/química , Colo/efeitos dos fármacos , Emodina/análogos & derivados , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/toxicidade , Folhas de Planta/química , Animais , Colo/microbiologia , Colo/patologia , Relação Dose-Resposta a Droga , Emodina/administração & dosagem , Emodina/toxicidade , Fezes/microbiologia , Crescimento , Masculino , Ratos , Ratos Endogâmicos F344
19.
Int J Radiat Biol ; 93(7): 665-675, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28281393

RESUMO

PURPOSE: To assess the radiosensitizing effect of the biguanide drug metformin used alone or in combination with reactive oxygen species (ROS) modifying agents N-acetyl-L-cysteine (NAC) or emodin, and contrasted to the mitochondrial complex 1 inhibitor rotenone in altering the radiation responses of the p53 wild-type SA-NH and p53 mutant FSa mouse tumor lines grown either in vitro or in vivo. MATERIALS AND METHODS: Tumor cells were grown to confluence in vitro and exposed to a single 4 Gy dose in the presence or absence of metformin (5 mM) and ROS modifiers or to 10 Gy with or without metformin as tumors in the flanks of C3H mice using a tumor growth delay assay. RESULTS: Both metformin and rotenone protected SA-NH (p < .001) while sensitizing FSa (p < .001) to 4 Gy. Neither NAC nor emodin altered metformin's action. Metformin was also directly toxic to FSa cells (p = .002). In contrast, in vivo metformin (250 mg/kg) sensitized both SA-NH (9-day growth delay, p < .05) and FSa (4-day growth delay, p < .05) tumors if administered 1 h before irradiation. CONCLUSION: Metformin effects on tumor cells measured under in vitro conditions may differ from those determined in vivo due to p53 and heterogeneous environmental factors.


Assuntos
Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Metformina/administração & dosagem , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/radioterapia , Proteína Supressora de Tumor p53/metabolismo , Acetilcisteína/administração & dosagem , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Emodina/administração & dosagem , Feminino , Camundongos , Camundongos Endogâmicos C3H , Neoplasias Experimentais/patologia , Doses de Radiação , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/administração & dosagem
20.
Fish Shellfish Immunol ; 62: 75-85, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28065629

RESUMO

We determined the effects of emodin on the cell viability, respiratory burst activity, mRNA levels of antioxidative enzymes (Cu-Zn SOD, CAT and NOX2), and gene expressions of the Nrf2-Keap1 signaling molecules in the peripheral blood leukocytes of blunt snout bream. Triplicate groups of cultured cells were treated with different concentrations of emodin (0.04-25 µg/ml) for 24 h. Results showed that the emodin caused a dramatic loss in cell viability, and occurred in a dose-dependent manner. Emodin exposure (1-25 µg/ml) were significantly induced the ROS generation compared to the control. The respiratory burst and NADPH oxidase activities were significantly induced at a concentration of 0.20 µg/ml, and inhibited at 25 µg/ml. Besides, mRNA levels of antioxidant enzyme genes were dramatically regulated by emodin exposure for 24 h. During low concentrations of exposure, mRNA levels of Cu-Zn SOD in the cells treated with 0.04, 0.20 µg/ml, CAT, NOX2 and Nrf2 in the cells treated with 1 µg/ml were sharply increased, respectively. Whereas, high concentrations were dramatically down-regulated the gene expressions of CAT in the cells treated with 5, 25 µg/ml and NOX2 in the cells treated with 25 µg/ml. Furthermore, sharp increase in Keap1and Bach1 expression levels were observed a dose-dependent manner. In conclusion, this study demonstrated that emodin could induce antioxidant defenses which were involved in cytotoxic activities, respiratory burst and the transcriptional regulation levels of antioxidant enzymes and Nrf2-Keap1 signaling molecules.


Assuntos
Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cyprinidae , Emodina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Emodina/administração & dosagem , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/enzimologia , Leucócitos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo
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