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1.
Environ Toxicol ; 35(9): 922-929, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32293791

RESUMO

Excessive fluoride exposure contributes to neurotoxic effects. Emodin exhibits antioxidative functions in the central nervous system (CNS); however, its neuroprotective mechanism against fluoride remains to be elucidated. Our aim was to explore the neuroprotective efficacy and the possible mechanisms of emodin. In our study, synaptic proteins and oxidative stress damage were examined after human neuroblastoma SH-SY5Y cells were treated with high doses of NaF for 24 hours. Moreover, pretreatment with emodin was used to shed light on the neuroprotective effects in NaF-induced toxicity in SH-SY5Y cells. We found that NaF significantly lowered the protein expressions of SNAP 25, synaptophysin and PSD 95 in SH-SY5Y cells. In addition, NaF exposure increased the protein expression of p-ERK1/2 and decreased the protein expressions of Nrf2 and HO-1, as well as facilitated increasing ROS, 4-hydroxynonenal (4-HNE), and 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Pretreatment with emodin significantly recovered these alterations caused by NaF. These data implied that the neuroprotective effects of emodin and pointed to the promising utilization for protecting against neurotoxicity induced by fluoride.


Assuntos
Emodina/farmacologia , Fluoretos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neuroblastoma/metabolismo , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Espécies Reativas de Oxigênio/metabolismo , Sinapses/metabolismo , Sinapses/patologia , Sinaptofisina/metabolismo
3.
Asian Pac J Cancer Prev ; 21(1): 205-210, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31983185

RESUMO

OBJECTIVE: New drugs for cancer treatment are being sought worldwide. Therapeutic agents derived from natural substances can provide cost-efficient options. We evaluated the effect of emodin, an active natural anthraquinone derivate, and it's in-silico homologue the novel substance BTB14431 in vivo. METHOD: CC-531 colon cancer cells were implanted intraperitoneal (ip) and subcutaneous (sc) in 100 WAG/Rij rats. 28 days after tumor cell implantation, solid cancers were treated for 7 days by varying doses of BTB14431 (0.3 mg/kg body weight; 1.7 mg/kg) or emodin (2.5 mg/kg; 5 mg/kg). Treatment was applied either via an intravenous (iv) port catheter or by ip injection. Saline solution served as control. 21 days after final dose all animals were euthanized and ip tumor weight, sc tumor weight and animal body weight (bw) were determined by autopsy. Significant lower total tumor weight occurred after iv treatment with low dose BTB14431 (6.8 g; 90% confidence interval (CI) 5.3 - 8.2 g; p ≤ 0.01) and also low and high concentrations of emodin (9.4 g; CI 7.9 - 10.7 g; p ≤ 0.01 and 8.3 g; CI 7.6 - 9.3; p ≤ 0.01). Iv treatment by high dose BTB14431 did not lead to a decline in tumor weight. High dose ip treatment by emodin led to a lower overall (11.1 g; CI 10.1 - 13.8 g; p ≤ 0.01) and ip tumor weight (8.6 g; CI 6 - 10.4 g; p ≤ 0.01). Sc tumor weight was not affected. All other ip treatments did not result in changes of combined, ip or sc tumor weight. Bw decreased during iv treatment in all animals and increased after treatment was completed. Regain of bw was stronger in animals receiving low dose emodin. CONCLUSION: Our study shows promising anti-cancer properties of BTB14431 and supports the evidence regarding emodin as a natural antitumorigenic agent. Optimal dosing of iv emodin and especially BTB 14431 for maximal efficacy remains unclear and should be a subject of further research. 
.


Assuntos
Apoptose , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Emodina/análogos & derivados , Emodina/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ratos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Ultrason Sonochem ; 62: 104861, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31796325

RESUMO

Emodin is a bioactive compound with strong anti-inflammatory and antioxidant properties. Micellar casein is casein concentrates close to the native state of casein micelles. The interaction of emodin and micellar casein under heat treatment in the absence and presence of ultrasound was investigated, and the properties of microencapsulated emodin in micellar casein were compared. Fluorescence experiments proved that the major interaction between emodin and micellar casein was through hydrophobic forces under heat treatment in the absence and presence of ultrasound. However, ΔH, ΔS and ΔG of emodin-casein complexation without sonication were higher than those with sonication, in contradiction to binding constants. The particle sizes of emodin-casein complexes in the presence of ultrasound were smaller than those without sonication, while the specific surface area showed an opposite trend. As to encapsulation, emodin-casein capsules under heat-sonication treatment showed higher antioxidant properties than those of heat treatment alone under similar experimental conditions. Interestingly, micellar casein-emodin encapsulation in the presence of ultrasound showed a lower release rate of emodin in gastrointestinal conditions than that without ultrasound at the emdoin concentration of 10 µmol per gram casein. Ultrasound has been shown to be a potential processing technology for customizing the release kinetics of bioactive compounds.


Assuntos
Caseínas/química , Emodina/química , Temperatura Alta , Micelas , Ondas Ultrassônicas , Antioxidantes/farmacologia , Caseínas/farmacologia , Formas de Dosagem , Emodina/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Difração de Pó , Ligação Proteica , Análise Espectral/métodos , Termodinâmica
5.
Oxid Med Cell Longev ; 2019: 3765898, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827674

RESUMO

Background: Aloin exerts considerable protective effects in various disease models, and its effect on hepatic ischemia-reperfusion (HIR) injury remains unknown. This research is aimed at conducting an in-depth investigation of the antioxidant, anti-inflammatory, and antiapoptosis effects of aloin in HIR injury and explain the underlying molecular mechanisms. Methods: In vivo, different concentrations of aloin were intraperitoneally injected 1 h before the establishment of the HIR model in male mice. The hepatic function, pathological status, oxidative stress, and inflammatory and apoptosis markers were measured. In vitro, aloin (AL, C21H22O9) or lipopolysaccharide (LPS) was added to a culture of mouse primary hepatocytes before it underwent hypoxia/reoxygenation (H/R), and the apoptosis in the mouse primary hepatocytes was analyzed. Results: We found that 20 mg/kg was the optimum concentration of aloin for mitigating I/R-induced liver tissue damage, characterized by decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Aloin pretreatment substantially suppressed the generation of hepatic malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and IL-6 and enhanced the hepatic superoxide dismutase (SOD) activities as well as glutathione (GSH) and IL-10 levels in the liver tissue of I/R mice; this indicated that aloin ameliorated I/R-induced liver damage by reducing the oxidative stress and inflammatory response. Moreover, aloin inhibited hepatocyte apoptosis and inflammatory response that was caused by the upregulated expression of Bcl-2, the downregulated expression of cleaved caspase3(C-caspase3), Bax, Toll-like receptor 4 (TLR4), FADD, MyD88, TRAF6, phosphorylated IKKα/ß (p-IKKα/ß), and phosphorylated nuclear factor κB p65 (p-NF-κB p65).


Assuntos
Emodina/análogos & derivados , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Emodina/farmacologia , Glutationa/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/metabolismo
6.
Life Sci ; 237: 116893, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606381

RESUMO

AIM: Gastric cancer (GC) is a common human malignancy tumor of digestive tract in worldwide. Physcion 8-O-ß-glucopyranoside (PG) exhibits anti-tumor effects in various cancer cells. This study aimed to explore the biological behavior effects of PG on GC cells, and determine its underlying mechanism. MATERIAL AND METHODS: The effect of PG treatment on the ferroptotic GC cell death was detected by ROS level, intracellular Fe2+ level and malondialdehyde (MDA) generation in vitro. The mRNA expression was detected by RT-qPCR. The interaction between miR-103a-3p and glutaminase 2 (GLS2) were verified by dual-luciferase reporter gene assay. Cell proliferation, invasion and migration were examined by CCK-8 and Transwell assay. Western blot was used to examine the expression of GLS2, SLC1A5 and epithelial-mesenchymal transition (EMT) related proteins. We also evaluated the influence of PG on the tumor growth and metastasis in vivo. RESULTS: PG-induced ferroptosis in GC cells through upregulating ROS level, intracellular Fe2+ level and MDA generation. Besides, PG also significantly enhanced the protein level of GLS2, which was an important transporter of glutamine to glutamate. Importantly, miR-103a-3p directly interacted with GLS2 and suppressed its expression. Mechanistically, PG treatment significantly promoted ferroptosis and anti-tumorigenesis by downregulating inhibitory effect of miR-103a-3p on GLS2 expression. CONCLUSION: Our studies confirmed that PG exerts pro-ferroptosis and anti-tumor effects in vitro and in vivo through regulating miR-103a-3p/GLS2 axis, thereby highlighting its therapeutic potential in GC.


Assuntos
Apoptose/efeitos dos fármacos , Emodina/análogos & derivados , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Glutaminase/metabolismo , Ferro/metabolismo , MicroRNAs/genética , Neoplasias Gástricas/patologia , Animais , Proliferação de Células/efeitos dos fármacos , Emodina/farmacologia , Feminino , Glutaminase/genética , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Inflammation ; 42(6): 2129-2138, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605249

RESUMO

There is no specific drug to treat severe acute pancreatitis (SAP), which induces substantial medical and social burden. Many studies have reported the beneficial effects of emodin against SAP in vivo and in vitro. However, the underlying mechanism has been unclear. This paper described the design and implementation of anti-inflammatory and antioxidant activity of emodin. Emodin restored the pathological damage of SAP and simultaneously decreased the high levels of serum amylase, lipase, TNF-α, and IL-18 in the peripheral blood of SAP rat. Emodin reversed reactive oxygen species (ROS) in neutrophils derived from SAP rat. The levels of voltage-dependent anion channel 1 (VDAC1), NOD-like receptor protein 3 (NLRP3), caspase-1, and IL-18 were examined to analyze the change of inflammasome-related mediators between SAP and emodin treatment. These findings suggest that emodin plays its protective role on SAP against oxidative stress and inflammasome signals.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Emodina/farmacologia , Pancreatite/tratamento farmacológico , Amilases/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Emodina/uso terapêutico , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-18/sangue , Estresse Oxidativo/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Ratos , Fator de Necrose Tumoral alfa/sangue
8.
J Orthop Surg Res ; 14(1): 319, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601256

RESUMO

BACKGROUND: Laminectomy is usually classed as a common orthopedic surgery, but postoperative epidural fibrosis often leads to less-than-desirable clinical outcomes. As demonstrated by prior studies, emodin (EMO) exerts an anti-fibrotic effect. Here, we carried out investigation into the inhibitory effect created by EMO application on epidural fibrosis after laminectomy in rats. METHODS: The paper conducts a series of experiment. In vitro, we observed the effect of EMO on fibroblasts by Cell Counting Kit-8 (CCK-8) assay. Apoptosis of fibroblasts induced by EMO was detected by western blot, TUNEL assay, and flow cytometry. The results revealed that EMO was capable of inducing fibroblast apoptosis, and the proteins of PERK pathway also changed accordingly. In vivo, the effect of EMO on epidural fibrosis in 12 male Sprague-Dawley rats was observed by histological staining. RESULTS: CCK-8 assay indicated that EMO was effective in reducing fibroblast viability in a time- and a dose-dependent manner. TUNEL assay and flow cytometry analysis have demonstrated that the apoptotic rate of fibroblasts increased as the EMO concentration rose. Western blot analysis proved that EMO promoted the relative expression of p-perk and p-eIF2α and that the expression of its downstream proteins CHOP and GRP78 was also enhanced. The expression of apoptotic protein Bax and cleaved PARP was upregulated, whereas the expression of anti-apoptotic protein Bcl-2 was downregulated. In addition, histological and immunohistochemical analysis demonstrated that EMO functioned to inhibit epidural fibrosis and increase GRP78 expression in fibrous tissue by promoting apoptosis of fibroblasts. CONCLUSIONS: EMO could have inhibitory effect on epidural fibrosis in a concentration-dependent manner. The potential mechanism might be through PERK signaling pathway to promote fibroblast apoptosis. It has a possibility to be taken as a novel method for the treatment of epidural fibrosis.


Assuntos
Emodina/uso terapêutico , Espaço Epidural/efeitos dos fármacos , Laminectomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Emodina/farmacologia , Estresse do Retículo Endoplasmático , Espaço Epidural/metabolismo , Espaço Epidural/patologia , Fibroblastos/efeitos dos fármacos , Fibrose , Proteínas de Choque Térmico/metabolismo , Humanos , Masculino , Inibidores de Proteínas Quinases/farmacologia , Ratos Sprague-Dawley
9.
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
10.
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
11.
Drug Des Devel Ther ; 13: 3171-3180, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564833

RESUMO

Background: Emodin, a major component of Polygonum multiflorum (PM), has been reported to exert both protective and toxic effects in several cell types. However, the effects and underlying mechanisms of action of emodin in hepatic cells are still obscure. Methods: The present study used the normal human liver cell line L02 to investigate the effects and mechanisms of emodin in hepatic cells. After treatment with emodin, L02 cells were examined for viability, apoptosis and autophagy with the Cell Counting Kit-8 (CCK-8), annexin V/PerCP staining and GFP-LC3 plasmid transfection. The expression of proteins including cleaved caspase-3, LC3B-I/II, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and actin was examined by using Western blot. Results: Emodin significantly inhibited the viability of and induced apoptosis in L02 cells in a dose- and time-dependent manner. In addition, emodin increased the number of GFP-LC3 puncta in L02 cells and upregulated the expression of LC3B-II compared to those in control cells. Furthermore, emodin significantly decreased the expression of p-PI3K, p-AKT and p-mTOR in a dose-dependent manner compared to that in control cells without altering the expression of PI3K, AKT and mTOR. Notably, cotreatment with emodin and 3-methyladenine (3-MA) or rapamycin significantly increased and decreased the apoptosis rate of L02 cells, respectively, compared to that of cells treated with emodin alone. Conclusion:  In conclusion, emodin exhibited cytotoxicity in the L02 human hepatic cell line by promoting apoptosis, and it also induced autophagy through the suppression of the PI3K/AKT/mTOR signalling pathway. The autophagy could play a protective role following emodin treatment.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Emodina/farmacologia , Hepatócitos/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Emodina/química , Fallopia multiflora/química , Hepatócitos/metabolismo , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo
12.
PLoS One ; 14(7): e0219866, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365567

RESUMO

This study aimed to investigate the function of ATP-binding cassette (ABC) transporter genes in grass carp treated with emodin combined with diazinon (DZN) exposure. The transcription levels of five ABC transporter genes in different tissues of grass carp and at different time points were measured by real-time quantitative PCR (qRT-PCR). The analysis of different tissues showed higher ABCB1 expression in the skin (26-fold) and gill (2-fold) than in the liver. In addition, ABCB11 expression was higher in the skin (109-fold) and gill (57-fold) than in the liver, ABCC1 was more highly expressed in the gill (50-fold) than in the liver, and ABCG2 was expressed at higher levels in the skin (659-fold, p < 0.01), gill (628-fold, p < 0.01) and liver (659-fold, p < 0.01) than in brain tissue. The analysis of different time points revealed that the ABCB1, ABCB11, ABCC1, ABCC2 and ABCG2 genes were highly expressed at 24 h in the liver in the experimental group. However, analysis of the intestinal tissue of the experimental group showed that the expression of ABCB1 and ABCB11 peaked at 6 h, the expression of ABCC1 and ABCC2 peaked at 5 d, and the expression of ABCG2 peaked at 3 d. Furthermore, the emodin concentrations in the liver and intestine reached their peak levels (50.18 and 117.24 µg·ml-1, respectively) after 48 and 1 h of treatment with emodin combined with DZN, respectively. The peak DZN concentrations in the liver (1.42 ng·ml-1) and intestine (0.2 ng·ml-1) were detected 3 and 6 h after emodin treatment combined with DZN, respectively. In conclusion, this study shows that the transcript levels of ABC transporters respond to the presence of emodin, which indicates their potential involvement in and contribution with the metabolic process in grass carp.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Carpas/metabolismo , Diazinon/toxicidade , Emodina/farmacologia , Proteínas de Peixes/genética , Expressão Gênica/efeitos dos fármacos , Inseticidas/toxicidade , Transportadores de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Animais , Carpas/genética , Diazinon/metabolismo , Emodina/metabolismo , Feminino , Proteínas de Peixes/metabolismo , Brânquias/química , Brânquias/metabolismo , Inseticidas/metabolismo , Fígado/química , Fígado/metabolismo , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Pele/química , Pele/metabolismo
13.
Phytother Res ; 33(11): 2960-2970, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31410907

RESUMO

Although the approved hepatitis B virus (HBV)-polymerase inhibitors (e.g., lamivudine) often lead to drug-resistance, several natural products have shown promising efficacies. Though Aloe vera (AV) gel and its constituents are shown inhibitors of many viruses, their anti-HBV activity still remains elusive. We therefore, tested the anti-HBV potential of AV extract and its anthraquinones in hepatoma cells, including molecular docking, high-performance thin layer chromatography (HPTLC), and cytochrome P450 (CYP3A4) activation analyses. Our anti-HBV assays (HBsAg/HBeAg Elisa) showed maximal inhibition of viral antigens production by aloe-emodin (~83%) > chrysophanol (~62%) > aloin B (~61%) > AV extract (~37%) in HepG2.2.15 cells. Interestingly, the effect of aloe-emodin was comparable with lamivudine (~86%). Moreover, sequential treatment with lamivudine (pulse) followed by aloe-emodin (chase) enhanced the efficacy of monotherapy by ~12%. Docking (AutoDock Vina) of the anthraquinones indicated strong interactions with HBV-polymerase residues that formed stable complexes with high Gibbs's free energy. Further, identification of aloe-emodin and aloin B by validated HPTLC in AV extract strongly endorsed its anti-HBV potential. In addition, our luciferase-reporter gene assay of transfected HepG2 cells showed moderate induction of CYP3A4 by aloe-emodin. In conclusion, this is the first report on anti-HBV potential of AV-derived anthraquinones, possibly via HBV-polymerase inhibition. Of these, although aloin B exhibits novel antiviral effect, aloe-emodin appears as the most promising anti-HBV natural drug with CYP3A4 activating property towards its enhanced therapeutic efficacy.


Assuntos
Aloe/química , Antraquinonas/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Antraquinonas/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Linhagem Celular , Emodina/análogos & derivados , Emodina/farmacologia , Emodina/uso terapêutico , Células Hep G2 , Humanos , Fitoterapia/métodos , Extratos Vegetais/farmacologia
14.
Phytomedicine ; 64: 152904, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31454654

RESUMO

BACKGROUND: Millions of people are infected by the influenza virus worldwide every year. Current selections of anti-influenza agents are limited and their effectiveness and drug resistance are still of concern. PURPOSE: Investigation on in vitro and in vivo effect of aloin from Aloe vera leaves against influenza virus infection. METHODS: In vitro antiviral property of aloin was measured by plaque reduction assay in which MDCK cells were infected with oseltamivir-sensitive A(H1N1)pdm09, oseltamivir-resistant A(H1N1)pdm09, H1N1 or H3N2 influenza A or with influenza B viruses in the presence of aloin. In vivo activity was tested in H1N1 influenza virus infected mice. Aloin-mediated inhibition of influenza neuraminidase activity was tested by MUNANA assay. Aloin treatment-mediated modulation of anti-influenza immunity was tested by the study of hemagglutinin-specific T cells in vivo. RESULTS: Aloin significantly reduced in vitro infection by all the tested strains of influenza viruses, including oseltamivir-resistant A(H1N1)pdm09 influenza viruses, with an average IC50 value 91.83 ± 18.97 µM. In H1N1 influenza virus infected mice, aloin treatment (intraperitoneal, once daily for 5 days) reduced virus load in the lungs and attenuated body weight loss and mortality. Adjuvant aloin treatment also improved the outcome with delayed oseltamivir treatment. Aloin inhibited viral neuraminidase and impeded neuraminidase-mediated TGF-ß activation. Viral neuraminidase mediated immune suppression with TGF-ß was constrained and influenza hemagglutinin-specific T cell immunity was increased. There was more infiltration of hemagglutinin-specific CD4+ and CD8+ T cells in the lungs and their production of effector cytokines IFN-γ and TNF-α was boosted. CONCLUSION: Aloin from Aloe vera leaves is a potent anti-influenza compound that inhibits viral neuraminidase activity, even of the oseltamivir-resistant influenza virus. With suppression of this virus machinery, aloin boosts host immunity with augmented hemagglutinin-specific T cell response to the infection. In addition, in the context of compromised benefit with delayed oseltamivir treatment, adjuvant aloin treatment ameliorates the disease and improves survival. Taken together, aloin has the potential to be further evaluated for clinical applications in human influenza.


Assuntos
Aloe/química , Antivirais/farmacologia , Emodina/análogos & derivados , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Neuraminidase/antagonistas & inibidores , Animais , Linhagem Celular , Farmacorresistência Viral , Emodina/farmacologia , Hemaglutininas/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/enzimologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/enzimologia , Vírus da Influenza B/imunologia , Influenza Humana/imunologia , Influenza Humana/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Oseltamivir/farmacologia , Folhas de Planta/química , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Proteínas Virais/antagonistas & inibidores
15.
Med Sci Monit ; 25: 5621-5629, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31354164

RESUMO

BACKGROUND This study investigated the effects and underlying mechanisms of emodin on cough variant asthma (CVA) in mice. MATERIAL AND METHODS The bronchial asthma mouse model was successfully established by use of ovalbumin (OVA) sensitization and challenge. The BALB/c mice were divided into 6 groups: a control group, an OVA model without or with emodin (15, 30, 60 mg/kg) group, and a dexamethasone (0.5 mg/g) group. The effect of the treatment was determined by measuring airway responsiveness. The levels of immunoglobulin molecules, as well as inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum, were determined by ELISA. The lung tissues were stained by hematoxylin-eosin (HE). The expressions of Notch receptors (Notch 1-3) and Delta-like (DLL) 4 in the lung tissues were detected by RT-PCR and Western blot analysis. RESULTS Compared with the model group, emodin treatment significantly increased the levels of immunoglobulin E (IgE) and IgG1/IgG2a in BALF and serum (p<0.05). HE results indicated that emodin inhibited the infiltration of inflammatory cells and that emodin reduced the levels of inflammatory cytokines, interleukin (IL)-5, IL-17, and interferon (IFN)-γ in BALF and serum (p<0.05). Furthermore, the expressions of Notch 1, 2, 3, and DLL4 in lung tissue were inhibited by emodin treatment. CONCLUSIONS The results demonstrated that emodin alleviated inflammation in CVA mice, which might be associated with suppression of the Notch pathway. Emodin might be a promising therapeutic agent for allergic asthma.


Assuntos
Asma/tratamento farmacológico , Emodina/farmacologia , Receptores Notch/metabolismo , Animais , Asma/metabolismo , Asma/patologia , Líquido da Lavagem Broncoalveolar , Tosse/tratamento farmacológico , Tosse/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/metabolismo , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Inflamação/metabolismo , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia
16.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2820-2826, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359696

RESUMO

The aim of this study was to explore the effect of emodin on lipid accumulation and inflammation in hepatocytes. The cell morphology was observed by microscopy. LDH release was detected by the kit. Levels of intracellular lipid droplets were observed by oil red O staining. The contents of TC and TG in cells were detected by the kit. Western blot was used to determine protein expressions of FASN,SREBF2,APOB,IL-6 and p-NF-κB in hepatocytes. The results showed that the levels of L02 cell LDH were significantly increased after being treated with emodin,and the cells showed shrinkage,volume reduction,decrease in quantity with the increase of dose. Red lipid droplets were observed in L02 hepatocytes. Intracellular TC and TG contents of L02 cell increased in a concentrationdependent manner,with significant differences between medium and high-dose groups( P < 0. 05). Protein expressions of FASN,SREBF2,IL-6 and p-NF-κB were significantly higher than those of the control group,and the expression level of APOB was significantly lower than that of the control group( P<0. 05). In conclusion,emodin could induce lipid accumulation and inflammatory damage in hepatocytes in a dose-dependent manner,which in turn could damage liver cells. This process was related to the up-regulation of FASN,SREBF2,IL-6,p-NF-κB,as well as the down-regulation of the protein expression of APOB.


Assuntos
Emodina/farmacologia , Hepatócitos/efeitos dos fármacos , Metabolismo dos Lipídeos , Apolipoproteína B-100/metabolismo , Células Cultivadas , Ácido Graxo Sintase Tipo I/metabolismo , Hepatócitos/metabolismo , Humanos , Inflamação , Interleucina-6/metabolismo , Lipídeos , NF-kappa B/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
17.
Colloids Surf B Biointerfaces ; 182: 110364, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352254

RESUMO

In this study, we have encapsulated natural physcion (PHY) drug loading into metal-organic frameworks MOFs, zeolitic imidazolate frameworks (ZIFs) through straight-forward nano-precipitation technique. The synthesized PHY@ZIF-8 indicated high drug loading encapsulation efficiency i.e. 88%, whereas, drug loading capacity was found to be 11.49%. The characterization of PHY loaded-ZIF 8 (PHY@ZIF-8) was carried out by powder x-ray diffraction (PXRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and FT-IR methods. The release of PHY loaded in ZIF-8 was 88.72% at pH 5.0 which is approximately three time higher than its release in physiological system with pH 7.4 (27.61%). The remarkable stability of PHY@ZIF-8 NPs even after 25 days stem it as an effective and stable candidate. Furthermore, the antibacterial activity of pure PHY, ZIF-8 and PHY@ZIF-8 were investigated against gram negative strains and gram positive strain. The PHY@ZIF-8 showed maximum growth inhibition zones against all microorganism as compare to pure PHY. We hope that this model drug could have the potential ability for treatment of various infectious diseases.


Assuntos
Anti-Infecciosos/farmacologia , Emodina/análogos & derivados , Imidazóis/química , Estruturas Metalorgânicas/química , Zeolitas/química , Anti-Infecciosos/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Emodina/química , Emodina/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Cinética , Testes de Sensibilidade Microbiana , Pseudomonas putida/efeitos dos fármacos , Pseudomonas putida/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
18.
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
19.
Eur J Pharmacol ; 859: 172525, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31288005

RESUMO

Emodin can effectively inhibit colorectal cancer cells, but the mechanism remains elusive. This study analyzed the changes of VEGFR2 signaling pathways in patients with colorectal cancer and the effects of emodin on HCT116 cells and xenograft tumor model. The expression levels of VEGFR2, PI3K, and p-AKT in colorectal cancer tissue samples were significantly higher than those in adjacent normal ones. Docking simulation confirmed that emodin bound the hydrophobic pocket and partially overlapped with the binding sites of VEGFR2, thus disrupting VEGFR2 dimerization. Western blotting further confirmed that emodin significantly inhibited the expression of VEGFR2, and reduced the expressions of PI3K and p-AKT in HCT116 cells. Furthermore, it suppressed the growth, adhesion and migration of HCT116 cells. In addition, emodin inhibited the tumor growth in xenograft model and the expressions of VEGFR2, PI3K and p-AKT in vivo. In conclusion, emodin suppressed the growth of colorectal cancer cells by inhibiting VEGFR2, as a potential candidate for therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/patologia , Emodina/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Antineoplásicos/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Emodina/metabolismo , Células HCT116 , Humanos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Conformação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Artif Cells Nanomed Biotechnol ; 47(1): 2855-2865, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31299866

RESUMO

We planned to dig the carcinostasis activity of physcion 8-O-ß-glucopyranoside (PG) in ovarian cancer cells and explored whether long non-coding RNA NORAD was the potential cause of the carcinostasis impact of PG. The impacts of PG on the tumour cell behaviours (including cell viability, apoptosis, migration and invasion) of SKOV3 cells were grabbed. The levels of NORAD in cancer tissues and cell lines were determined; afterwards, the impacts of abnormal expression of NORAD on the tumour cell behaviours of SKOV3 cells were assessed. Moreover, we explored whether NORAD modulated the level of STAT3 by competitively sponging miR-608, thus mediating the antineoplastic effects of PG on ovarian cancer cells. PG suppressed cell viability, enhanced apoptosis and lessened migration and invasion of SKOV3 cells. NORAD was upregulated in ovarian cancer tissues and cells. Silencing of NORAD lessened cell viability, migration and invasion, but induced apoptosis of SKOV3 cells, whereas overexpression of NORAD had opposite effects. Moreover, PG decreased the expression of NORAD. Overexpression of NORAD reversed the effects of PG treatment on the cell biological performances of SKOV3 cells, which were further reversed after overexpression of miR-608 simultaneously. Furthermore, STAT3 was tested as a target gene of miR-608, and the impact of NORAD in PG-treated SKOV3 cells were through the miR-608-mediated STAT3. Our findings reveal that NORAD/miR-608/STAT3 axis is pivotal in mediating the antineoplastic impacts of PG on ovarian cancer cells, which may offer a novel explanation in the therapy of ovarian cancer.


Assuntos
Antineoplásicos/farmacologia , Emodina/análogos & derivados , Glucosídeos/farmacologia , MicroRNAs/genética , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Emodina/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Regulação para Cima/efeitos dos fármacos
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