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1.
Int J Mol Sci ; 23(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35055102

RESUMO

Astaxanthin is a lipid-soluble carotenoid influencing lipid metabolism, body weight, and insulin sensitivity. We provide a systematic analysis of acute and chronic effects of astaxanthin on different organs. Changes by chronic astaxanthin feeding were analyzed on general metabolism, expression of regulatory proteins in the skeletal muscle, as well as changes of excitation and synaptic activity in the hypothalamic arcuate nucleus of mice. Acute responses were also tested on canine cardiac muscle and different neuronal populations of the hypothalamic arcuate nucleus in mice. Dietary astaxanthin significantly increased food intake. It also increased protein levels affecting glucose metabolism and fatty acid biosynthesis in skeletal muscle. Inhibitory inputs innervating neurons of the arcuate nucleus regulating metabolism and food intake were strengthened by both acute and chronic astaxanthin treatment. Astaxanthin moderately shortened cardiac action potentials, depressed their plateau potential, and reduced the maximal rate of depolarization. Based on its complex actions on metabolism and food intake, our data support the previous findings that astaxanthin is suitable for supplementing the diet of patients with disturbances in energy homeostasis.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Anabolizantes/farmacologia , Metabolismo Energético/efeitos dos fármacos , Animais , Cães , Ingestão de Alimentos/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Especificidade de Órgãos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Xantofilas/farmacologia
2.
Int J Mol Sci ; 23(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35008943

RESUMO

Flubendazole, belonging to benzimidazole, is a broad-spectrum insect repellent and has been repurposed as a promising anticancer drug. In recent years, many studies have shown that flubendazole plays an anti-tumor role in different types of cancers, including breast cancer, melanoma, prostate cancer, colorectal cancer, and lung cancer. Although the anti-tumor mechanism of flubendazole has been studied, it has not been fully understood. In this review, we summarized the recent studies regarding the anti-tumor effects of flubendazole in different types of cancers and analyzed the related mechanisms, in order to provide the theoretical reference for further studies in the future.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Mebendazol/análogos & derivados , Animais , Antineoplásicos/química , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Monitoramento de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mebendazol/química , Mebendazol/farmacologia , Mebendazol/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Especificidade de Órgãos/efeitos dos fármacos , Transdução de Sinais , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Int J Biol Macromol ; 194: 276-288, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34848240

RESUMO

Soybean (Glycine max) harbours high quality proteins which have been evident to exhibit therapeutic properties in alleviating many diseases including but not limited to diabetes and its related metabolic complications. Since diabetes is often manifested with hyperglycemia, impaired energy homeostasis and even low-grade chronic inflammation, plenty of information has raised the suggestion for soy protein supplementation in preventing and controlling these abnormalities. Moreover, clinical intervention studies have established a noteworthy correlation between soy protein intake and lower prevalence of diabetes. Besides soy protein, various soy-derived peptides also have been found to trigger antidiabetic response in different in vitro and in vivo models. Molecular mechanisms underlying the antidiabetic actions of soy protein and peptide have been predicted in many literatures. Results demonstrate that components of soy protein can act in diversified ways and modulate various cell signaling pathways to bring energy homeostasis and to regulate inflammatory parameters associated with diabetic pathophysiology. The main objective of the present review lies in a systemic understanding of antidiabetic role of soy protein and peptide in the context of impaired glucose and lipid metabolism, and inflammation.


Assuntos
Glycine max/química , Hipoglicemiantes/farmacologia , Peptídeos/farmacologia , Proteínas de Soja/farmacologia , Animais , Glicemia/efeitos dos fármacos , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Especificidade de Órgãos/efeitos dos fármacos , Peptídeos/química , Peptídeos/uso terapêutico , Proteínas de Soja/química , Proteínas de Soja/uso terapêutico
4.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360801

RESUMO

Senna and rhubarb are often used as routine laxatives, but there are differences in mechanism of action and potential side effects. Here, we studied metabolites of senna anthraquinones (SAQ), rhubarb anthraquinones (RAQ) and their chemical marker, sennoside A (SA), in a rat diarrhea model. In in vitro biotransformation experiments, SAQ, RAQ and SA were incubated with rat fecal flora solution and the metabolites produced were analyzed using HPLC. In in vivo studies, the same compounds were investigated for purgation induction, with measurement of histopathology and Aqps gene expression in six organs. The results indicated that SAQ and RAQ had similar principal constituents but could be degraded into different metabolites. A similar profile of Aqps down-regulation for all compounds was seen in the colon, suggesting a similar mechanism of action for purgation. However, in the kidneys and livers of the diarrhea-rats, down-regulation of Aqps was found in the RAQ-rats whereas up-regulation of Aqps was seen in the SAQ-rats. Furthermore, the RAQ-rats showed lower Aqp2 protein expression in the kidneys, whilst the SA-rats and SAQ-rats had higher Aqp2 protein expression in the kidneys. This may have implications for side effects of SAQ or RAQ in patients with chronic kidney or liver diseases.


Assuntos
Aquaporina 2/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/metabolismo , Fígado/metabolismo , Rheum/química , Senna/química , Senosídeos/farmacologia , Animais , Masculino , Especificidade de Órgãos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Senosídeos/química
5.
Int J Biol Macromol ; 181: 644-652, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798576

RESUMO

In nature, heavy metals significantly affect crop growth and quality. Among various heavy metals, copper (Cu) is both essential and toxic to plants depending on the concentration and complex homeostatic networks. The Cu transporter family (COPT) plays important roles in Cu homeostasis, including absorption, transportation, and growth in plants; however, this gene family is still poorly understood in alfalfa (Medicago sativa L.). In this study, a total of 12 MsCOPTs were identified and characterized. Based on the conserved motif and phylogenetic analysis, MsCOPTs could be divided into four subgroups (A1, A2, A3, and B). Gene structure, chromosomal location, and synteny analyses of MsCOPTs showed that segmental and tandem duplications likely contributed to their evolution. Tissue-specific expression analysis of MsCOPT genes indicated diverse spatiotemporal expression patterns. Most MsCOPT genes had high transcription levels in roots and nodules, indicating that these genes may play vital roles in the absorption and transport of Cu through root. The complementary heterologous expression function of yeast once again indicates that root-specific COPT can supplement the growth of defective yeast strains on YPEG medium, suggesting that these genes are Cu transporters. In summary, for the first time, our research identified COPT family genes at the whole-genome level to provide guidance for effectively improving the problem of Cu deficiency in the grass-livestock chain and provide theoretical support for the subsequent development of grass and animal husbandry.


Assuntos
Proteínas de Transporte de Cobre/genética , Medicago sativa/genética , Medicago sativa/fisiologia , Metais Pesados/toxicidade , Família Multigênica , Proteínas de Plantas/genética , Estresse Fisiológico/genética , Sequência de Aminoácidos , Cromossomos de Plantas/genética , Proteínas de Transporte de Cobre/química , Proteínas de Transporte de Cobre/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genoma de Planta , Medicago sativa/efeitos dos fármacos , Mutação/genética , Motivos de Nucleotídeos , Especificidade de Órgãos/efeitos dos fármacos , Especificidade de Órgãos/genética , Filogenia , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Mapas de Interação de Proteínas/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Estresse Fisiológico/efeitos dos fármacos
6.
Molecules ; 26(4)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668635

RESUMO

Launaea nudicaulis is used in folk medicine worldwide to treat several diseases. The present study aimed to assess the antidiabetic activity of L. nudicaulis ethanolic extract and its effect on diabetic complications in streptozotocin-induced hyperglycemic rats. The extract was orally administrated at 250 and 500 mg/kg/day for 5-weeks and compared to glibenclamide as a reference drug at a dose of 5 mg/kg/day. Administration of the extract exhibited a potential hypoglycemic effect manifested by a significant depletion of serum blood glucose concurrent with a significant elevation in serum insulin secretion. After 5-weeks, extract at 250 and 500 mg/kg/day decreased blood glucose levels by about 53.8 and 68.1%, respectively, compared to the initial values (p ≤ 0.05). The extract at the two dosages prevented weight loss of rats from the 2nd week till the end of the experiment, compared to diabetic control rats. The extract further exhibited marked improvement in diabetic complications including liver, kidney and testis performance, oxidative stress, and relative weight of vital organs, with respect to diabetic control. Histopathological examinations confirmed the previous biochemical analysis, where the extract showed a protective effect on the pancreas, liver, kidney, and testis that degenerated in diabetic control rats. To characterize extract composition, UPLC-ESI-qTOF-MS identified 85 chromatographic peaks belonging to flavonoids, phenolics, acyl glycerols, nitrogenous compounds, and fatty acids, with four novel phenolics reported. The potential anti-diabetic effect warrants its inclusion in further studies and or isolation of the main bioactive agent(s).


Assuntos
Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Etanol/química , Hipoglicemiantes/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Hipoglicemiantes/farmacologia , Insulina/sangue , Rim/efeitos dos fármacos , Rim/fisiopatologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Malondialdeído/sangue , Metabolômica , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos Wistar , Estreptozocina , Testes de Toxicidade Aguda
7.
Nutrients ; 13(1)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467650

RESUMO

This paper continues the systematic review on proanthocyanidins and flavan-3-ols in the prevention and treatment of periodontal disease and covers the immunomodulatory effects, and animal- and clinical studies, while the other part discussed the direct antibacterial properties. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response are covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies is analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there are still only a few animal and clinical studies. Most of the reports, regardless of the used model, indicated the efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontal disease is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.


Assuntos
Flavonoides/farmacologia , Flavonoides/uso terapêutico , Imunomodulação/efeitos dos fármacos , Periodontite/tratamento farmacológico , Periodontite/prevenção & controle , Proantocianidinas/farmacologia , Proantocianidinas/uso terapêutico , Animais , Biomarcadores , Estudos Clínicos como Assunto , Citocinas/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Flavonoides/química , Humanos , Mediadores da Inflamação/metabolismo , Metaloproteinases da Matriz/metabolismo , Especificidade de Órgãos/efeitos dos fármacos , Periodontite/etiologia , Periodontite/metabolismo , Proantocianidinas/química , Resultado do Tratamento
8.
Molecules ; 27(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35011338

RESUMO

Along with the increased knowledge about the positive health effects of food bioactives, the eating habits of many individuals have changed to obtain higher nutritional benefits from foods. Fruits are among the most preferred food materials in this regard. In particular, berry fruits are important sources in the diet in terms of their high nutritional content including vitamins, minerals, and phenolic compounds. Berry fruits have remedial effects on several diseases and these health-promoting impacts are associated with their phenolic compounds which may vary depending on the type and variety of the fruit coupled with other factors including climate, agricultural conditions, etc. Most of the berries have outstanding beneficial roles in many body systems of humans such as gastrointestinal, cardiovascular, immune, and nervous systems. Furthermore, they are effective on some metabolic disorders and several types of cancer. In this review, the health-promoting effects of bioactive compounds in berry fruits are presented and the most recent in vivo, in vitro, and clinical studies are discussed from a food science and nutrition point of view.


Assuntos
Frutas/química , Avaliação do Impacto na Saúde , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Sistema Cardiovascular/efeitos dos fármacos , Suplementos Nutricionais , Metabolismo Energético/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Promoção da Saúde , Humanos , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Valor Nutritivo , Especificidade de Órgãos/efeitos dos fármacos , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/análise
9.
Molecules ; 27(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35011479

RESUMO

This study evaluated the in vitro antineoplastic and antiviral potential and in vivo toxicity of twelve extracts with different polarity obtained from the herbaceous perennial plant Geum urbanum L. (Rosaceae). In vitro cytotoxicity was determined by ISO 10993-5/2009 on bladder cancer, (T-24 and BC-3C), liver carcinoma (HEP-G2) and normal embryonic kidney (HEK-293) cell lines. The antineoplastic activity was elucidated through assays of cell clonogenicity, apoptosis induction, nuclear factor kappa B p65 (NFκB p65) activation and total glutathione levels. Neutral red uptake study was applied for antiviral activity. The most promising G. urbanum extract was analyzed by UHPLC-HRMS. The acute in vivo toxicity analysis was carried out following OEDC 423. The ethyl acetate extract of aerial parts (EtOAc-AP) exhibited the strongest antineoplastic activity on bladder cancer cell lines (IC50 = 21.33-25.28 µg/mL) by inducing apoptosis and inhibiting NFκB p65 and cell clonogenicity. EtOAc and n-butanol extracts showed moderate antiviral activity against human adenovirus type 5 and human simplex virus type I. Seventy four secondary metabolites (gallic and ellagic acid derivatives, phenolic acids, flavonoids, etc.) were identified in EtOAc-AP by UHPLC-HRMS. This extract induced no signs of acute toxicity in liver and kidney specimens of H-albino mice in doses up to 210 mg/kg. In conclusion, our study contributes substantially to the detailed pharmacological characterization of G. urbanum, thus helping the development of health-promoting phytopreparations.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antivirais/farmacologia , Geum/química , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Antivirais/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Especificidade de Órgãos/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Espectrometria de Massas em Tandem
10.
Biomed Res Int ; 2020: 1976298, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029493

RESUMO

BACKGROUND: Withania frutescens. L (W. frutescens) is a perennial woody medicinal plant belonging to family Solanaceae largely used by the indigenous population to Morocco for the treatment of disease. OBJECTIVE: The purpose of this study was to investigate the chemical composition, acute, and subacute toxicity of W. frutescens extract in mice. MATERIALS AND METHODS: The phytochemical composition of W. frutescens extract was determined using a gas chromatograph (GC/MS). Acute toxicity study was carried out in mice through oral administration of single doses 500 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was performed with oral administration of repeated doses 500 and 2000 mg/kg/day for 28 days. Biochemical parameters (alanine aminotransferase, aspartate aminotransferase, urea, and creatinine), as well as histopathological changes potentially occurred in organs, (liver, kidney, and spleen) were evaluated. RESULTS: The results of chromatographic analysis showed the richness of W. frutescens extract in interesting phytochemical compounds majorly constituted of bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-(C10H16). Regarding acute toxicity study, the results showed no clinical symptoms occurred in treated mice compared to the control group and no histological changes detected in analyzed organs of treated mice with dose put to 2000 mg/kg nor adverse effect on biochemical parameters. CONCLUSION: The outcome of this work showed no toxic effect of W. frutescens in mice up to dose 2000 mg/kg bodyweight. Therefore, this study could scientifically validate further traditional use with safety in the range of tested doses.


Assuntos
Compostos Fitoquímicos/análise , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda , Withania/química , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Raízes de Plantas/química
11.
Oxid Med Cell Longev ; 2020: 1813798, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908623

RESUMO

Hemp seed has been used as a traditional oriental medicine and health food in China for centuries. Polysaccharides from hemp seed (HSP) exhibit important properties of intestinal protection, but there are limited data on the specific underlying mechanism. The primary objective of this study was to investigate the protective effect of HSP on intestinal oxidative damage induced by cyclophosphamide (Cy) in mice. The results showed that pretreatment with HSP significantly increased the average daily gain, thymus index, spleen index, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity in serum and ileal homogenate and significantly reduced malondialdehyde (MDA) content in ileal homogenate. In addition, the expression levels of SOD, GSH-Px, Nrf2, heme oxidase-1 (HO-1), and quinoneoxidoreductase-1 (NQO1) mRNA in ileal homogenate were significantly increased. Western blot results showed that HSP significantly upregulated the expression of Nrf2 protein and downregulated the expression of Keap1 protein in the ileum. Collectively, our findings indicated that HSP had protective effects on intestinal oxidative damage induced by Cy in mice, and its mechanism might be related to the activation of Nrf2-Keap1 signaling pathway.


Assuntos
Cannabis/química , Ciclofosfamida/efeitos adversos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Sementes/química , Transdução de Sinais , Animais , Peso Corporal/efeitos dos fármacos , Catalase/sangue , Glutationa Peroxidase/sangue , Íleo/metabolismo , Inativação Metabólica/genética , Jejuno/efeitos dos fármacos , Jejuno/ultraestrutura , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Monossacarídeos/análise , Especificidade de Órgãos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Superóxido Dismutase/sangue
12.
Oxid Med Cell Longev ; 2020: 7680276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922654

RESUMO

The effects of selenium nanoparticles (SeNPs) on the antioxidant capacity in Sprague-Dawley (SD) rats were investigated. The rats were given intragastric administration of an SeNP suspension at doses of 0, 2, 4, and 8 mg Se/kg BW for two weeks. The antioxidant capacity in serum and organic tissues (liver, heart, and kidney) and the gene expression levels of glutathione peroxidase 1 (GPX1) and glutathione peroxidase 4 (GPX4) in the liver were measured. Buffalo rat liver (BRL) cell lines were further constructed to explore the cytotoxicity mechanism induced by SeNPs through the determination of antioxidant capacity; cell activity; apoptosis; and Caspase-3, Caspase-8, and Caspase-9 family activities. The results showed that SeNP administration over 4.0 mg Se/kg BW decreased the antioxidant capacities in the serum, liver, and heart and downregulated mRNA expression of GPX1 and GPX4 in the liver. The BRL cell line experiments showed that treatment with over 24 µM SeNPs decreased the viability of the cells and damaged the antioxidant capacity. Flow cytometry analysis showed that decreased cell viability induced by SeNPs is mainly due to apoptosis, rather than cell necrosis. Caspase-3 and Caspase-8 activities were also increased when BRL cells were treated with 24 µM and 48 µM SeNPs. Taken together, a nonlethal level of SeNPs could impair the antioxidant capacity in serum and organic tissues of rats, and the liver is the most sensitive to the toxicity of SeNPs. A pharmacological dose of SeNPs could lead to cytotoxicity and induce cell death through apoptosis and extrinsic pathways contributing to SeNP-induced apoptosis in BRL cells.


Assuntos
Hepatócitos/patologia , Fígado/patologia , Nanopartículas Metálicas/química , Selênio/farmacologia , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/ultraestrutura , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Masculino , Nanopartículas Metálicas/ultraestrutura , Especificidade de Órgãos/efeitos dos fármacos , Oxirredução , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Glutationa Peroxidase GPX1
13.
Oxid Med Cell Longev ; 2020: 6059058, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850001

RESUMO

This study assessed the molecular mechanism of selenium (Se) protecting against kidney injury induced by zearalenone (ZEA) in mice. The experimental mice were divided into 4 groups including the control group, the Se group, the ZEA group, and the Se+ZEA group; ZEA and Se were administered orally for 28 days. The changes in renal biochemical index (BUN, UA, and CRE), biochemical change of kidney damage such as BUN, UA, and CRE, and oxidative damage such as MDA, T-SOD, and GSH-Px were investigated. Pathological sections and TUNEL staining were used to analyze renal pathological changes and cell apoptosis. qRT-PCR and Western blot were employed to detect the expression of genes and proteins which were related with endoplasmic reticulum stress. The results showed that ZEA increased the concentration of BUN, UA, and CRE and the content of MDA and decreased the activities of T-SOD and GSH-Px in the mouse kidneys. However, Se reversed above changes of the biochemical and antioxidant indexes of renal injury. Moreover, the results also showed that ZEA can increase the expression of Bax, caspase-12, caspase-3, Bip, CHOP, JNK protein, and mRNA and decrease the expression of Bcl-2 protein and mRNA. But Se reversed these proteins and genes related to endoplasmic reticulum stress and apoptosis. It can be concluded that Se protected against the kidney damage induced by ZEA. Se may protect the kidney from ZEA-induced apoptosis and oxidative stress by inhibiting ERS.


Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Selênio/farmacologia , Zearalenona/toxicidade , Animais , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
14.
Sci Rep ; 10(1): 3305, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094371

RESUMO

Excessive nitrogen (N) input and irrigation exacerbate N leaching in winter wheat production in the North China Plain (NCP). To explore the optimal N for better N remobilization and higher N utilization of wheat under water-saving irrigation will be conductive to less environmental contamination. A field experiment was conducted at 300 (N300), 240 (N240), 180 (N180), and 0 (N0) kg N ha-1 of N application under supplemental irrigation (SI) that brought the relative soil water content (RSWC) to 70% at jointing and 65% at anthesis. Compared with N0, N180 improved the free amino acid content in the flag leaf and grain after anthesis, dry matter and plant N accumulation at maturity, N translocation amount of vegetable organs and its contribution to grain from anthesis to maturity. Compared to N240 and N300, N180 increased the N translocation efficiency of vegetable organs, and reduced the soil NO3-N residue in the 60-180 cm soil layer, which contributing to no significant reduction in grain yield and grain protein yield, but higher grain N recovery efficiency (GREN), N recovery efficiency (REN), and N partial factor productivity (PFPN). Positive relationships were found between leaf N translocation efficiency and grain yield, grain protein yield, PFPN, GREN, and REN. Therefore, N180 is appropriate to obtain a steady grain yield over 7.5 t ha-1 for at least 2 years under SI based on RSWC in the NCP.


Assuntos
Irrigação Agrícola , Nitrogênio/farmacologia , Triticum/fisiologia , Aminoácidos/análise , Biomassa , China , Nitratos/metabolismo , Especificidade de Órgãos/efeitos dos fármacos , Folhas de Planta/química , Solo/química , Triticum/efeitos dos fármacos , Triticum/crescimento & desenvolvimento
15.
Biochem Biophys Res Commun ; 523(4): 829-834, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-31954515

RESUMO

The cytokine-like protein FAM19A5 is highly expressed in the brain, but little is known about its functions there. Here, we found that FAM19A5 was expressed in mouse hypothalamic cells expressing proopiomelanocortin (POMC) and neuropeptide Y (NPY)/agouti-related peptide (AgRP), and in the microglia. Tumor necrosis factor-α (TNF-α), which induces inflammatory sickness responses, greatly increased hypothalamic expression of FAM19A5. Knockdown of FAM19A5 expression resulted in decreased TNF-α-induced anorexia, body weight loss and TNF-α-induced expression of inflammatory factors. In contrast, intracerebroventricular administration of FAM19A5 induced anorexia, body weight loss and hyperthermia, together with increased expression of inflammatory factors. FAM19A5 injection also induced increases in c-fos activation and POMC mRNA level in hypothalamic POMC neurons. Together, these results suggest that FAM19A5 plays an important role in hypothalamic inflammatory responses.


Assuntos
Citocinas/metabolismo , Hipotálamo/metabolismo , Hipotálamo/patologia , Inflamação/metabolismo , Animais , Citocinas/administração & dosagem , Citocinas/farmacologia , Humanos , Hipotálamo/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Especificidade de Órgãos/efeitos dos fármacos , Pró-Opiomelanocortina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Fator de Necrose Tumoral alfa/administração & dosagem
16.
Int J Biol Macromol ; 147: 233-240, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31923517

RESUMO

The polysaccharide (OJP1), extracted from the root of Ophiopogon japonicus, is a well-known traditional Chinese medicine used to treat cardiovascular diseases. The present study was set up to investigate the cardioprotective effect of OJP1 on isoproterenol (ISO)-induced myocardial ischemia injury in rats. Results showed that pretreatment with OJP1 (100, 200 and 300 mg/kg) significantly reduced ISO-induced ST-segment elevation and the heart index, attenuated the levels of marker enzymes (AST, LDH, CK and CK-MB), along with a significantly enhanced the activities of ATPases. Moreover, pretreatment with OJP1 not only enhanced the activities of SOD, GPx and CAT in serum and myocardium, but also decreased the level of MDA. The biochemical and histopathological analysis also showed that OJP1 can alleviate the myocardial injury induced by ISO. Taken together, our results indicated that oral administration of OJP1 offered significant cardioprotective effect against the damage induced by ISO through enhancement of endogenous antioxidants.


Assuntos
Cardiotônicos/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Ophiopogon/química , Polissacarídeos/uso terapêutico , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , ATPase de Ca(2+) e Mg(2+) , Cardiotônicos/farmacologia , Catalase/metabolismo , Eletrocardiografia , Endotelina-1/metabolismo , Glutationa Peroxidase/metabolismo , Isoproterenol , Malondialdeído/metabolismo , Isquemia Miocárdica/sangue , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/diagnóstico por imagem , Miocárdio/enzimologia , Miocárdio/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Especificidade de Órgãos/efeitos dos fármacos , Polissacarídeos/farmacologia , Ratos Sprague-Dawley , Albumina Sérica Humana/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/metabolismo
17.
Biomed Res Int ; 2020: 4521586, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33506006

RESUMO

BACKGROUND: The aim of this work was to study the toxic effects and target organs of Mosla chinensis Maxim (MCM) in rats and provide theoretical basis for clinical medication. METHODS: The subchronic toxicity study was conducted on 60 male and female SD rats using the fixed-dose method for the treatment groups and 20 male and female SD rats for the control. At the subchronic toxicity study, the water extract of MCM with fixed doses of 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day was administered for 90 days intragastric, and the control group was given the same amount of distilled water. After 90 days, the general conditions of the rats were observed. Assessment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occurrence in gut flora and urine metabolism. RESULTS: There was no significant difference in physical signs, reactivity, and stool characteristics in the four groups. Compared with the control group, the number of red blood cells in the male 2 g/kg/day group and the female 0.2 g/kg/day group was significantly different (P < 0.05). The detection of serum biochemical indicators showed that MCM has an effect on liver and kidney function but has no physiological significance. The level of low-density lipoprotein in male rats was lower than that in the control group (P < 0.05). Compared with the control group, the blood glucose levels of female rats in the 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day groups were significantly increased (P < 0.05). As far as the diversity of intestinal flora is concerned, feeding MCM for 90 days has an influence on the distribution of intestinal flora. The content of lactic acid bacteria increased, and the ratio of hard bacteria to Bacteroides (f/b) was also affected, but there was no significant difference. CONCLUSIONS: These findings showed that the long-term intragastric administration of the MCM is safe to use within its dose recommendation. But it could have a slight effect on the metabolism of uric acid by changing the composition of intestinal flora and affecting the metabolism of tryptophan.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Lamiaceae/química , Testes de Toxicidade Crônica , Animais , Biomarcadores/sangue , Biomarcadores/urina , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Testes Hematológicos , Imunidade/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Especificidade de Órgãos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Análise de Componente Principal , Ratos Sprague-Dawley
18.
Biol Trace Elem Res ; 193(1): 44-63, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30877523

RESUMO

Arsenic (As) and cadmium (Cd) are elements arousing major public health concerns associated with environmental pollution, high toxicity potential, and carcinogenic nature. However, selenium (Se) at low doses and incorporated into enzymes and proteins has antioxidant properties and protects animals and humans from the risk of various diseases. It also has an exceptionally narrow range between necessary and toxic concentrations, which is a well-known hindrance in its use as a dietary supplement. The present article aims to update and expand the role of Se in As and Cd toxicity discussed in our earlier paper. In general, recent reports show that Se, regardless of its form (as selenite, selenomethionine, nanoSe, or Se from lentils), can reduce As- or Cd-mediated toxicity in the liver, kidney, spleen, brain, or heart in animal models and in cell culture studies. As was suggested in our earlier review, Se antagonizes the toxicity of As and Cd mainly through sequestration of these elements into biologically inert complexes and/or through the action of Se-dependent antioxidant enzymes. An increase in the As methylation efficiency is proposed as a possible mechanism by which Se can reduce As toxicity. However, new studies indicate that Se may also diminish As or Cd toxicity by activation of the Nrf2 pathway. In addition, this paper discusses possible signs of Se toxic effects, which may be a challenge for its future use in the therapy of As and Cd poisoning and provide future directions to address this issue.


Assuntos
Arsênio/toxicidade , Cádmio/toxicidade , Selênio/farmacocinética , Selênio/uso terapêutico , Antioxidantes/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Especificidade de Órgãos/efeitos dos fármacos
19.
J Trace Elem Med Biol ; 58: 126439, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31830704

RESUMO

BACKGROUND: Studies in mammals proved dietary organic selenium (Se) being superior to inorganic Se regarding effects on growth performance, antioxidative status, immune response, and Se homeostasis. However, the picture of possible effects of different Se sources and - levels can be expanded. The present field study evaluated the effects on weight gain, hematological and selected biochemical variables as well as plasma concentrations of vitamin E (vitE), total Se and selenobiomolecules in piglets throughout the suckling period. METHODS: Piglets were monitored from birth to 38 days of age (d). The mother sows' diets were enriched with l-selenomethionine (SeMet-0.26 and -0.43 mg Se/kg feed) or sodium selenite (NaSe-0.40 and -0.60 mg Se/kg feed) from 1 month prior to farrowing until the end of lactation period. Piglets received pelleted feed supplemented with Se similarly to the sows' diets from one week of age. Selenite at 0.40 mg Se/kg (NaSe-0.40) represents a common Se source and -level in pig feed and served as control diet. RESULTS: From 24d, piglets in SeMet-groups had higher mean body weight (BW) compared with piglets from sows fed NaSe-0.40. Furthermore, from five-d and above, piglets from sows fed NaSe-0.60 had significantly higher BW than offspring from sows fed NaSe-0.40. Neonatal piglets in group SeMet-0.43 had significantly lower red blood cell counts (RBC), hemoglobin (Hgb) and hematocrit (Hct) concentrations compared with piglets from sows fed with NaSe-0.40. Neonatal and 5d-old piglets in group SeMet-0.26 showed higher gamma-glutamyl transferase activity than piglets in group NaSe-0.40. From five d and above, group NaSe-0.60 excelled with increased specific hematological variables culminating at age 38d with increased Hct, mean corpuscular volume (MCV), and MC hemoglobin (MCH) as well as increased activities of aspartate transaminase and lactate dehydrogenase compared with the other groups. Generally, offspring in the SeMet groups had higher total Se-concentrations in plasma than those from sows fed selenite, and showed a dose-response effect on plasma Se-concentrations. Furthermore, SeMet-fed piglets had higher plasma levels of the selenoproteins (Sel) glutathione peroxidase 3 (GPx3) and SelP as well as selenoalbumin. Plasma vitE levels were significantly negatively correlated with RBC throughout trial period. CONCLUSIONS: Maternal supplementation with SeMet during gestation influenced hematology and clinical biochemistry in neonatal piglets in a different way than in offspring from sows receiving selenite enriched diets. Growth performance was positively influenced by both dietary Se source and Se level. Higher plasma levels of GPx3 observed in piglets receiving SeMet probably improved the protection against birth or growth related oxidative stress. These might prime the piglets for demanding situations as indicated by higher weight gain in offspring from sows fed with SeMet-supplemented diets. Our results on some enzyme activities might indicate that piglets fed NaSe-0.60 had to cope with increased levels of oxidative stress compared with those originating from sows fed SeMet or lower dietary levels of selenite. We assume that combining inorganic and organic Se sources in complete feed for breeding sows might be beneficial fro reproduction and the offspring's performance.


Assuntos
Antioxidantes/metabolismo , Comportamento Alimentar , Selenometionina/farmacologia , Selenito de Sódio/farmacologia , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Dieta/veterinária , Especificidade de Órgãos/efeitos dos fármacos , Selênio/sangue , Suínos/sangue , Vitamina E/sangue
20.
Int J Mol Sci ; 20(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547612

RESUMO

The aim of this study was to analyze the analgesic potential of Arrabidaea chica extract (EHA) as an alternative to osteoarthritis (OA) treatment. Thus, the extract was initially evaluated by the cyclooxygenase inhibition test. The analgesic effect of the extract, in vivo, was also verified in a model of OA induced by sodium monoiodoacetate (2 mg). EHA was administered to rats at doses of 50, 150, and 450 mg/kg between 3 and 25 days after OA induction. The animals were clinically evaluated every 7 days, euthanized at 29 days, and the liver, spleen, kidney and knee collected for histopathological analysis. The chemical composition of EHA was identified by HPLC-MS and the identified compounds submitted to molecular docking study. The results showed that the extract promoted cyclooxygenase inhibition and produced significant improvements in disability, motor activity, hyperalgesia, and OA-induced allodynia parameters, in addition to improvements in the radiological condition of the knees (but not observed in the histopathological study). Chemically the extract is rich in flavonoids. Among them, we evidence that amentoflavone showed very favorable interactions with the enzyme COX-2 in the in silico analysis. Thus, it is concluded that A. chica has important analgesic properties for the treatment of OA.


Assuntos
Bignoniaceae/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Flavonoides/farmacologia , Hiperalgesia/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/química , Modelos Animais de Doenças , Flavonoides/química , Hiperalgesia/induzido quimicamente , Hiperalgesia/diagnóstico por imagem , Ácido Iodoacético/toxicidade , Atividade Motora/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Osteoartrite/induzido quimicamente , Osteoartrite/diagnóstico por imagem , Extratos Vegetais/química , Ratos , Ratos Wistar
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