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1.
Vet Med Sci ; 7(3): 800-811, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33570254

RESUMO

A major mean to minimize feeding costs and faecal nitrogen excretion on poultry farms is to decrease the supplied dietary protein content. This, however, is associated with the declines in productive performance and systemic health indices. Sanguinarine may improve protein efficiency via decreasing the intestinal amino acid decarboxylation and stimulating the tryptophan-serotonin pathway. The present study was carried out to investigate the effects of dietary supplementation of sanguinarine on the performance, egg yolk biochemical parameters, serum enzyme activities, nutrient digestibility, ovarian follicles, and hepatic health indices in laying hens fed decremental levels of crude protein (CP). For this purpose, 180 laying hens were allocated into nine dietary treatments with four replicates of five birds each. The experimental treatments consisted of three levels of CP (85.0%, 92.5%, and 100% of Hy-Line W-36 manual recommendation) and three levels of sanguinarine (0.00, 3.75, and 7.50 mg/kg) in a 3 × 3 factorial arrangement administered during a 70-day feeding trial. Results showed that the decremental levels of CP led to significant increases in serum aspartate aminotransferase (p < .05), alanine aminotransferase, and alkaline phosphatase (p < .01) activities, egg yolk cholesterol concentration (p = .064), and hepatic fat and malondialdehyde (MDA) contents (p < .05). It also caused the significant declines in ileal dry matter (DM) digestibility (p < .05) and eggshell strength (p < .05), and also tended to decrease CP digestibility (p = .071), Haugh unit (p = .057) and egg production percentage (p = .062). The interaction effects of the experimental factors indicated that dietary supplementation of sanguinarine, especially at 7.50 mg/kg, led to significant improvements in serum aspartate aminotransferase and alanine aminotransferase activities (p < .01), egg yolk cholesterol (p < .001) and triglyceride (p < .05) concentrations, eggshell strength (p < .001), Haugh unit (p < .05), hepatic fat (p < .001) and MDA (p = .059) contents, ileal DM and CP digestibility (p < .01) as well as egg production, egg mass and feed conversion ratio (FCR; p < .05) in birds receiving decremental levels of CP. Taken together, the results indicate that dietary administration of sanguinarine could enhance productive performance via improving nutrient digestibility, hepatic health indices and fortifying systemic antioxidant capacity in laying hens fed low-CP diets.


Assuntos
Benzofenantridinas/metabolismo , Galinhas/fisiologia , Digestão/efeitos dos fármacos , Isoquinolinas/metabolismo , Fígado/efeitos dos fármacos , Nutrientes/fisiologia , Reprodução/efeitos dos fármacos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Benzofenantridinas/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Feminino , Isoquinolinas/administração & dosagem , Fígado/fisiologia , Distribuição Aleatória , Reprodução/fisiologia
2.
BMC Pharmacol Toxicol ; 22(1): 1, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407916

RESUMO

BACKGROUND: The development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge. The alkaloid nitidine chloride (NC), a component of a traditional Chinese medicine, has been shown to have anticancer properties, but doses at therapeutic levels have unacceptable side effects. Here we investigate folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FA) as a potential carrier for controlled delivery of the drug. METHODS: Synthesized TPGS-FA was characterized by FTIR, UV-visible and 1H NMR spectroscopy, and TPGS loaded with NC was evaluated for its ability to induce apoptosis in Huh7 cells by Annexin V/PI and MTT assays, and observed by laser scanning confocal microscopy and inverted phase contrast microscopy. RESULTS: TPGS-FA/NC complexes were prepared successfully, and were homogenious with a uniform size of ~ 14 nm diameter. NC was released from the TPGS-FA/NC complexes in a controlled and sustained manner under physiological conditions (pH 7.4). Furthermore, its cytotoxicity to hepatocarcinoma cells was greater than that of free NC. CONCLUSIONS: TPGS-FA is shown to be useful carrier for drugs such as NC, and TPGS-FA/NC could potentially be a potent and safe drug for the treatment of hepatocellular carcinoma.


Assuntos
Antineoplásicos/administração & dosagem , Benzofenantridinas/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Ácido Fólico/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/administração & dosagem , Vitamina E/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzofenantridinas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ácido Fólico/química , Humanos , Micelas , Nanopartículas/química , Vitamina E/química
3.
Arch Ital Urol Androl ; 92(3)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33016036

RESUMO

OBJECTIVES: The aim of this study was to analyse the role of two alkaloid, Protopine and Nuciferine, in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® (Hyperthermic IntraVEsical Chemotherapy) instillations. MATERIALS AND METHODS: From September 2017 to September 2019, 100 patients were prospectively randomized into two groups: Group A = Protopine and Nuciferine syrup, 10 ml, once a day, for 8 weeks; Group B = placebo (flavoured coloured water), 10 ml, once a day, for 8 weeks. The primary endpoint was the evaluation of the efficacy of the therapy with Protopine and Nuciferine in controlling of the irritative symptoms. The secondary endpoint was the evaluation of the influences of the treatment on the uroflowmetric parameters. RESULTS: The patients of Group A showed a better International Prostatic Symptoms Score (IPSS) score, a better control of urgency symptoms (PPIUS) and tolerate well the pain (VAS score). The treatment doesn't modify Uroflow-Qmax and seems to improve the Uroflow-Voided Volume (ml) without influencing the Uroflow-Post Void Residual volume (PVR). Moreover, the treatment with Protopine and Nuciferine has been proven to be effective in the treatment of overactive bladder (OAB) symptoms. Patients' evaluation of the two different treatments assessed with Patient Global Impression of Improvement questionnaire (PGI-I), demonstrated improvements in the Group A, while the Group B showed a lower satisfaction. CONCLUSIONS: Protopine and Nuciferine can be interesting nutraceutical compounds useful to control irritative and pain related symptoms of intravesical chemo/immunotherapy.


Assuntos
Aporfinas/administração & dosagem , Benzofenantridinas/administração & dosagem , Alcaloides de Berberina/administração & dosagem , Suplementos Nutricionais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Administração Intravesical , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
4.
PLoS One ; 15(6): e0234920, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559224

RESUMO

Sanguinarine is a bioactive compound as a quaternary benzophenanthridine alkaloid from plant of the Macleaya cordata, Papaveraceae family. The present study was conducted to investigate the effects of dietary sanguinarine supplementation on growth performance, serum biochemistry parameters, intestinal mucosal morphology and gut microbiome in yellow feathered broilers. Two hundred and seventy 1-d-old female broilers were randomly assigned to 3 treatments ① Basal diet (NG); ② Basal diet containing bacitracin methylene disalicylate (50mg/Kg diet) (ANT); ③ Basal diet containing sanguinarine (0.7 mg/ kg of feed) (SAG). The statistical results showed that dietary sanguinarine supplementation enhanced growth performance and decreased glucose, uric acid as well as urea nitrogen levels of broilers at 28d of age (P<0.05). The 16S rRNA gene sequence analysis revealed that sanguinarine significantly decreased the species from the phyla Bacteroidetes, and increased the species from phyla Firmicutes. Moreover, dietary sanguinarine supplementation improved mucosal morphology to achieve higher ratio of intestinal villus height to crypt depth (P < 0.05), and decreased the concentrations of TNF-α and IL-4 in jejunum mucosal. This study demonstrated that sanguinarine supplementation in the diet of yellow feathered broilers improved intestinal morphology and microbiota community structure to promote growth performance on 1-28d.


Assuntos
Anti-Infecciosos/farmacologia , Benzofenantridinas/farmacologia , Galinhas/microbiologia , Microbioma Gastrointestinal , Isoquinolinas/farmacologia , Jejuno/efeitos dos fármacos , Animais , Anti-Infecciosos/administração & dosagem , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/patogenicidade , Benzofenantridinas/administração & dosagem , Glicemia/metabolismo , Galinhas/crescimento & desenvolvimento , Suplementos Nutricionais , Feminino , Firmicutes/efeitos dos fármacos , Firmicutes/patogenicidade , Interleucina-4/genética , Interleucina-4/metabolismo , Isoquinolinas/administração & dosagem , Jejuno/crescimento & desenvolvimento , Jejuno/metabolismo , Jejuno/microbiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Ácido Úrico/sangue
5.
Molecules ; 25(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861525

RESUMO

Corydalis humosa Migo is a traditional Chinese medicine that clears away damp heat, relieves sore. Protopine (PRO) is an alkaloid component isolated from C. humosa Migo. However, the role of protopine in acute kidney injury (AKI) has not yet been reported. This study aims to investigate the effect and mechanism of protopine isolated from C. humosa Migo on lipopolysaccharide (LPS)-induced AKI in mice. Inflammation accumulation was assessed by small animal living imaging. The blood urea nitrogen (BUN), and serum creatinine (Scr) were measured to assess the effects of protopine on renal function in LPS-induced AKI. The levels of tumor necrosis factor (TNF), interleukin-2 (IL-2), interferon-γ (IFN-γ), and (interleukin-10) IL-10 in serum were detected by cytometric bead array. Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in primary kidney cells. The proportions of granulocytes, neutrophils, and macrophages in peripheral blood were examined to evaluate the effect of protopine on immune cells in mice with AKI. Toll-like receptor (TLR4) and apoptotic signaling pathway were detected by Western blot analysis. The results showed that protopine markedly improved the renal function, relieve inflammation, reversed inflammatory cytokines, transformed apoptosis markers, and regulated the TLR4 signaling pathway in mice with AKI induced by LPS. The protopine isolated from C. humosa Migo protected mice against LPS-induced AKI by inhibiting apoptosis and inflammation via the TLR4 signaling pathway, thus providing a molecular basis for a novel medical treatment of AKI.


Assuntos
Injúria Renal Aguda/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Benzofenantridinas/administração & dosagem , Alcaloides de Berberina/administração & dosagem , Corydalis/química , Lipopolissacarídeos/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Benzofenantridinas/química , Benzofenantridinas/farmacologia , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Citocinas/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/citologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Testes de Função Renal , Camundongos , Receptor 4 Toll-Like/metabolismo , Resultado do Tratamento
6.
J Vet Pharmacol Ther ; 42(2): 197-206, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30350369

RESUMO

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half-life (t1/2 ) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (Cmax ) of DHSA (2.49 ± 1.4 µg/L) was higher that of SA (1.89 ± 0.8 µg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h-1 ·kg-1 ) with a t1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.


Assuntos
Benzofenantridinas/farmacocinética , Galinhas/metabolismo , Isoquinolinas/farmacocinética , Administração Oral , Animais , Benzofenantridinas/administração & dosagem , Benzofenantridinas/sangue , Galinhas/sangue , Cromatografia Líquida de Alta Pressão/veterinária , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Feminino , Meia-Vida , Injeções Intravenosas/veterinária , Isoquinolinas/administração & dosagem , Isoquinolinas/sangue , Espectrometria de Massas/veterinária
7.
J Anim Physiol Anim Nutr (Berl) ; 102(6): 1666-1674, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30129225

RESUMO

This study was conducted to investigate the effects of dietary supplementation with Sangrovit® (SAG; minimum of 1.5% sanguinarine, a quaternary benzo[c]phenanthridine alkaloid extracted from Macleaya cordata) on growth performance, intestinal morphology, intestinal microflora and its metabolites of early-weaned piglets. A total of 20 healthy weaned piglets (Duroc× [Large White×Landrace]), weaned at 21 days of age with an average body weight (BW) of 6.52 ± 0.23 kg, were randomly assigned to receive either a corn-soybean meal basal diet (CTR) or a basal diet supplemented with 50 mg/kg SAG (SAG). During the 21-days trial, we collected and analysed intestinal tissues and the luminal digesta for their morphology and populations of gut microbiota, as well as for measuring the concentrations of short-chain fatty acids (SCFAs) and ammonia. Compared with the CTR group, supplementation with SAG improved average daily gains (p = 0.011) and average daily feed intake (p = 0.037). Piglets fed the SAG diet had an average lower value for crypt depth of the jejunum (p = 0.011) and greater values for villus height in the ileum (p = 0.015) and ratios of villus height to crypt depth in the jejunum (p < 0.01) and in the ileum (p = 0.027) than did animals receiving the CTR diet. The addition of SAG increased the amounts of Lactobacillus in the ileum (p = 0.033) and caecum (p < 0.01), and tended to increase the amounts of Bifidobacterium (p = 0.058) in the caecum, while decreasing the amounts of Escherichia coli (p = 0.046) and Salmonella spp. (p = 0.035) in the ileum, as well as Salmonella spp. (p = 0.029) in the caecum. Dietary supplementation with SAG enhanced (p < 0.05) the concentrations of acetate, propionate, butyrate and total SCFAs, and also tended to increase the level of valerate (p = 0.055 and p = 0.052) in the ileal and caecal contents when compared with the CTR group. Concentrations of ammonia also declined in the caecal (p = 0.037) and ileal (p = 0.046) digesta in response to SAG. These results indicate that feeding early-weaned piglets a SAG-supplemented diet can potentially improve their growth performance and intestinal morphology, and can modify the intestinal luminal environment in a beneficial manner.


Assuntos
Benzofenantridinas/farmacologia , Trato Gastrointestinal/efeitos dos fármacos , Isoquinolinas/farmacologia , Extratos Vegetais/química , Suínos/crescimento & desenvolvimento , Envelhecimento , Amônia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bactérias/classificação , Benzofenantridinas/administração & dosagem , Benzofenantridinas/química , Dieta/veterinária , Suplementos Nutricionais , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Isoquinolinas/administração & dosagem , Isoquinolinas/química , Distribuição Aleatória
8.
Phytother Res ; 32(1): 65-75, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29044876

RESUMO

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a complex that regulates several hundreds of genes, including those involved in immunity and inflammation, survival, proliferation, and the negative feedback of NF-κB signaling. Chelidonine, a major bioactive, isoquinoline alkaloid ingredient in Chelidonium majus, exhibits antiinflammatory pharmacological properties. However, its antiinflammatory molecular mechanisms remain unclear. In this work, we explored the effect of chelidonine on TNF-induced NF-κB activation in HCT116 cells. We found chelidonine inhibited the phosphorylation and degradation of the inhibitor of NF-κB alpha and nuclear translocation of RELA. Furthermore, by inhibiting the activation of NF-κB, chelidonine downregulated target genes involved in inflammation, proliferation, and apoptosis. Chelidonine also inhibited mitogen-activated protein kinase pathway activation by blocking c-Jun N-terminal kinase and p38 phosphorylation. These results suggest that chelidonine may be a potential therapeutic agent against inflammatory diseases in which inhibition of NF-κB activity plays an important role.


Assuntos
Benzofenantridinas/uso terapêutico , Alcaloides de Berberina/uso terapêutico , Células HCT116/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Apoptose , Benzofenantridinas/administração & dosagem , Benzofenantridinas/farmacologia , Alcaloides de Berberina/administração & dosagem , Alcaloides de Berberina/farmacologia , Humanos , Transdução de Sinais , Transfecção
9.
Clin Toxicol (Phila) ; 55(7): 676-677, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28426257

RESUMO

A previously healthy 86-year-old male was transported by ambulance to the trauma bay of the emergency department (ED) for profuse bleeding from the left temple. The ambulance crew raised concern that the volume and force of the bleed may suggest arterial involvement. The patient reported having applied a natural topical remedy to a mole two weeks prior at the recommendation of a naturopath. The patient described progressive blackening and swelling of the area in the days following the single application of the product. After gaining control of the bleeding in the ED, the area was found to have a raised, 2 cm eschar.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Benzofenantridinas/efeitos adversos , Queimaduras Químicas/etiologia , Cloretos/efeitos adversos , Neoplasias Faciais/tratamento farmacológico , Hemorragia/induzido quimicamente , Isoquinolinas/efeitos adversos , Nevo/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Compostos de Zinco/efeitos adversos , Administração Cutânea , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Benzofenantridinas/administração & dosagem , Queimaduras Químicas/diagnóstico , Queimaduras Químicas/terapia , Cloretos/administração & dosagem , Neoplasias Faciais/diagnóstico , Hemorragia/terapia , Humanos , Isoquinolinas/administração & dosagem , Masculino , Nevo/diagnóstico , Automedicação/efeitos adversos , Neoplasias Cutâneas/diagnóstico , Resultado do Tratamento , Compostos de Zinco/administração & dosagem
10.
Pharmacology ; 100(1-2): 14-24, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28334726

RESUMO

AIM: This study was designed to develop sanguinarine-loaded solid lipid nanoparticles (SG-SLNs) and investigate its gastroprotective effect on ethanol-induced gastric mucosal lesions in mice. METHODS: SG-SLNs were prepared by high temperature melt-cool solidification method using glycerol monostearate as the lipid and a combination of lecithin with poloxamer 188 as the surfactants. Solid lipid nanoparticles (SLNs) were designed at varying lipid concentrations (5, 10, 15, and 20 mg/mL), surfactant mixture concentrations (6, 12, and 18 mg/mL), and drug contents (5, 10, 15, and 20 mg/mL) in "one factor at a time" fashion. Ethanol-induced gastric ulcer model was performed on Kunming mice to examine the anti-inflammatory activity of SG-SLNs and compare it with sanguinarine (SG). RESULTS: The high temperature melt-cool solidification method provided consistent production of SLNs with smaller size and high entrapment efficiency (EE%). The composition of optimal formulation was 10 mg/mL lipid concentration, 18 mg/mL surfactant mixture concentration, and 15 mg/mL drug amount. The mean particle size and EE% of optimized formulation were 238 ± 10.9 nm and 79 ± 2.8%, respectively. Additionally, SG-SLNs significantly decreased tumor necrosis factor-alpha and interleukin-6 levels in the serum and gastric tissue, and reduced the content of NO in serum, and strengthened the protection of mucosal membrane. Moreover, SG-SLNs treatment markedly inhibited ethanol-induced nuclear factor-kappa B (NF-κB) activation when compared with SG. CONCLUSIONS: SLNs could be potentially applied as a delivery system of SG. The protective effect of SG-SLNs is due to the suppression of NF-κB expression and subsequent pro-inflammatory cytokines release.


Assuntos
Benzofenantridinas/farmacologia , Isoquinolinas/farmacologia , Lipídeos/química , Nanopartículas , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Benzofenantridinas/administração & dosagem , Química Farmacêutica/métodos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Etanol/toxicidade , Isoquinolinas/administração & dosagem , Lecitinas/química , Masculino , Camundongos , NF-kappa B/metabolismo , Tamanho da Partícula , Poloxâmero/química , Tensoativos/química
11.
J Anim Physiol Anim Nutr (Berl) ; 101(5): 936-948, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27272257

RESUMO

This study was carried out to assess the effects of different levels of sanguinarine on antioxidant indices, immunological responses, serum biochemical parameters, ileal microbial counts and jejunal morphology of laying hens fed on diets with different levels of crude protein (CP). A total of 180 laying hens were subjected into nine dietary treatments with four cages of five birds each. Experimental treatments consisted of three levels of CP (85.0, 92.5 and 100% of Hy-Line W36 manual recommendation) and three levels of sanguinarine (0.00, 3.75 and 7.50 mg/kg) as a 3 × 3 factorial arrangement of laying hens which fed during a 70-day feeding trial. The in vitro study showed that sanguinarine exhibited sevenfold and threefold decreased antioxidant activities to inhibit 2-2-diphenyl-1-picric hydrazyl free radical as well as ferric ion reducing rather than butylated hydroxyl toluene. Although using the decremental levels of CP caused the increase in heterophil-to-lymphocyte ratio (p < 0.01), dietary administration of sanguinarine could suppress the serum cholesterol and malondialdehyde concentrations as well as heterophil-to-lymphocyte ratio (p < 0.05). Additionally, decreasing CP content resulted in the decreased percentage of albumin (p < 0.05); however, it had no negative effects on humoral immunity. Nonetheless, feeding of at least 3.75 mg/kg sanguinarine led to the remarkable increases in serum gamma globulin concentration (p < 0.01) and secondary (p < 0.05) antibody titres against sheep red blood cells. Moreover, a decline in dietary CP content led to higher villi height and crypt depth (p < 0.05; p < 0.001) and consequently decreased villi height-to-crypt depth ratio (p < 0.001) than the optimum level (100% CP). In spite of the effects of sanguinarine on the suppression of Escherichia coli and Salmonella counts (p < 0.05), it markedly enhanced villi height-to-crypt depth ratio as well as lamina propria lymphatic follicles extent, simultaneously (p < 0.001). Therefore, in spite of the detrimental effects of feeding low-CP diets on lymphocytes and serum albumin percentages, and villi height-to-crypt depth ratio, the administration of incremental levels of sanguinarine could improve cellular and humoral immunity, decrease ileal microbial counts and in turn improve the intestinal health indices in laying hens.


Assuntos
Antioxidantes/metabolismo , Benzofenantridinas/farmacologia , Galinhas/fisiologia , Proteínas Alimentares/administração & dosagem , Isoquinolinas/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Benzofenantridinas/administração & dosagem , Dieta/veterinária , Proteínas Alimentares/farmacologia , Suplementos Nutricionais , Feminino , Íleo/efeitos dos fármacos , Íleo/microbiologia , Isoquinolinas/administração & dosagem , Jejuno/efeitos dos fármacos
12.
J Pharm Pharmacol ; 68(8): 1030-40, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27293067

RESUMO

OBJECTIVES: A novel magnetic targeting anti-tumour drug delivery system (Fe3 O4 /KCTS-CHE) was designed using magnetic Fe3 O4 /chitosan alpha-ketoglutaric acid (Fe3 O4 /KCTS) as carrier and chelerythrine (CHE) as an anti-tumour drug model. Moreover, the anti-tumour activities and mechanisms of Fe3 O4 /KCTS-CHE were investigated. METHODS: The preparation conditions of Fe3 O4 /KCTS-CHE microspheres were optimized by response surface methodology (RSM). The CHE drug release kinetics was evaluated by fitting the experimental data to standard release equations. The inhibitive activities of Fe3 O4 /KCTS-CHE microspheres against the HepG2 cells were estimated using MTT assay in vitro, and the mechanisms were studied using Hoechst 33258 staining. KEY FINDINGS: The optimum preparation conditions were 11.68 : 1 for Fe3 O4 /KCTS:CHE ratio, 4 : 1 for oil/water ratio and 50.03 min for the ultrasonic time. The drug loading content and entrapment efficiency under the optimal conditions were 23.3% and 50.9%. The best fit was Higuchi model for the microspheres. The inhibitive rate on HepG2 cells of Fe3 O4 /KCTS-CHE nanoparticles varied from 30.19 ± 2.64% to 70.46 ± 6.42% at different concentrations from 50 to 400 mg/l in 72 h. CONCLUSION: Fe3 O4 /KCTS-CHE exhibited effective anti-tumour activities against the HepG2 cells and induced cell apoptosis in HepG2 cells. Fe3 O4 /KCTS-CHE possess a high drug loading efficiency and entrapment efficiency, which are a new matrix for controlling release of drugs and a promising candidate for targeted drug delivery.


Assuntos
Benzofenantridinas/administração & dosagem , Quitosana , Sistemas de Liberação de Medicamentos , Óxido Ferroso-Férrico , Hepatoblastoma , Ácidos Cetoglutáricos , Neoplasias Hepáticas , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Benzofenantridinas/farmacologia , Benzofenantridinas/uso terapêutico , Chelidonium/química , Composição de Medicamentos , Células Hep G2 , Hepatoblastoma/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Microesferas , Nanocápsulas , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
13.
Int J Oncol ; 48(1): 399-408, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26573871

RESUMO

Recent studies have shown anticancer activity of apigenin by suppressing glucose transporter 1 (GLUT1) expression in cultured cancer cells; however, it is not clear whether apigenin can suppress glucose metabolism in lung cancer cells or sensitize them to inhibition of glutamine utilization-mediated apoptosis through metabolic and oxidative stress. We show that apigenin significantly decreases GLUT1 expression in mice. Furthermore, we demonstrate that apigenin induces growth retardation and apoptosis through metabolic and oxidative stress caused by suppression of glucose utilization in lung cancer cells. The underlying mechanisms were defined that the anticancer effects of apigenin were reversed by ectopic GLUT1 overexpression and galactose supplementation, through activation of pentose phosphate pathway-mediated NADPH generation. Importantly, we showed that severe metabolic stress using a glutaminase inhibitor, compound 968, was involved in the mechanism of sensitization by apigenin. Taken together, the combination of apigenin with inhibitors of glutamine metabolism may provide a promising therapeutic strategy for cancer treatment.


Assuntos
Apoptose/efeitos dos fármacos , Transportador de Glucose Tipo 1/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Apigenina/administração & dosagem , Benzofenantridinas/administração & dosagem , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/genética , Glutamina/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , NADP/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
J Drugs Dermatol ; 14(5): 453-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25942662

RESUMO

Sanguinarine has a history of use in both folk medicine and early dermatology for the treatment of cutaneous neoplasms. Applied indiscriminately, bloodroot is an escharotic agent with potential to cause extensive tissue necrosis. However, when used in a controlled fashion, sanguinarine imparts selective cytotoxic/anti-proliferative activity through multiple mechanisms against human/ murine melanoma. To exploit sanguinarine's observed activity against melanoma, a targeted delivery system is required. We present a sol-gel based nanoparticulate platform for encapsulating sanguinarine chloride(sang-np)-a targeted therapeutic capable of steady, reliable delivery of predictable quantities of drug over a sustained time period with minimal undesirable effects. Size and release kinetics of sang-np were characterized using dynamic light scattering and ultraviolet-visible spectroscopy respectively. In vitro efficacy of sang-np was assessed. At both 2 and 24 hours, free sanguinarine killed > 90% of B16 melanoma cells, assessed via MTT assay. At 2 hours, sang-np killed a portion of melanoma cells, increasing to percentages comparable to free sanguinarine by 24 hours. Control(empty) nanoparticles exerted minimal toxicity to melanoma cells at both time points. TUNEL assay revealed that treatment with both sanguinarine and sang-np induces apoptosis in B16 melanoma cells, suggesting that both treatments act via the same mechanism of action. These data confirm controlled release of sanguinarine from sang-np, as well as comparable efficacy and mechanism of action to sanguinarine alone. This suggests that nanoparticle delivery of sanguinarine may be a unique approach to capitalize on this potent agent's inherent anti-tumor activity and overcome many of the limitations with its current formulation.


Assuntos
Benzofenantridinas/administração & dosagem , Sistemas de Liberação de Medicamentos , Isoquinolinas/administração & dosagem , Melanoma Experimental/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzofenantridinas/farmacologia , Preparações de Ação Retardada , Difusão Dinâmica da Luz , Marcação In Situ das Extremidades Cortadas , Isoquinolinas/farmacologia , Melanoma Experimental/patologia , Camundongos , Nanocápsulas , Tamanho da Partícula , Neoplasias Cutâneas/patologia , Fatores de Tempo
15.
Anim Sci J ; 86(1): 92-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25228334

RESUMO

The aim of this study was to investigate the efficacy of Sangrovit(®) , a plant-derived feed additive, given throughout the nursery stage via feed at 15 ppm and 50 ppm, on the health status and performance of weaners against negative controls. In a 900-sow farrow-to-finish farm, a total of 864 piglets were divided into three groups: (i) negative controls (NC); (ii) Sang 15: same feed as NCs, plus 15 g Sangrovit(®) /t of feed; (iii) Sang 50: same feed as NCs plus 50 g Sangrovit(®) /t of feed. The results indicated that administration of 50 ppm(-) Sangrovit(®) had the most beneficial effects on growth performance in weaning pigs. Specifically there was increase of body weight and average daily gain, as well as reduction of feed conversion ratio. Blood analysis from the Sang groups and especially the Sang 50 group revealed low values of haptoglobin and serum amyloid A.


Assuntos
Ração Animal , Animais Lactentes/crescimento & desenvolvimento , Benzofenantridinas/farmacologia , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Aditivos Alimentares/farmacologia , Isoquinolinas/farmacologia , Suínos/crescimento & desenvolvimento , Suínos/metabolismo , Animais , Benzofenantridinas/administração & dosagem , Relação Dose-Resposta a Droga , Aditivos Alimentares/administração & dosagem , Haptoglobinas/metabolismo , Isoquinolinas/administração & dosagem , Proteína Amiloide A Sérica/metabolismo , Desmame
16.
Planta Med ; 79(8): 654-60, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23670624

RESUMO

Chelerythrine is a quaternary benzo[c]phenanthridine alkaloid which has many potent pharmacological effects and can dissolve well in water; dihydrochelerythrine has recently been identified as a chelerythrine metabolite in rat. Most methods of preparation of liposomes suffer from the drawback of poor incorporation of water-soluble drugs. The emulsion/solvent evaporation method is a relatively simple and efficient way to prepare liposomes loaded with hydrophilic drugs. The aim of this study was therefore to find a suitable formulation to enhance the incorporation of chelerythrine into liposomes by the emulsion/solvent evaporation method and so improve the therapeutic efficacy of chelerythrine. Results showed that the chelerythrine-liposome has been successfully prepared by the emulsion/solvent evaporation method: the entrapment efficiency of chelerythrine was higher at 78.6 %, and the drug loadings reached 7.8 %. The relative bioavailability of chelerythrine and its dihydro derivative in liposomes was significantly increased compared with that of the chelerythrine solution. The area under the plasma concentration-time curve values of chelerythrine and dihydrochelerythrine after oral administration of chelerythrine-liposomes were 4.83-fold and 2.02 higher than those obtained with the chelerythrine solution. The half time and peak concentrations of chelerythrine and dihydrochelerythrine were also higher for chelerythrine-liposomes than that for chelerythrine. In contrast, the total body clearance and apparent volume of distribution were lower for chelerythrine-liposomes in comparison to the respective parameters for the chelerythrine solution. It can thus be concluded that incorporation into liposomes prolonged chelerythrine retention within the systemic circulation.


Assuntos
Benzofenantridinas/farmacocinética , Administração Oral , Animais , Benzofenantridinas/administração & dosagem , Lipossomos , Microscopia Eletrônica , Tamanho da Partícula , Ratos , Soluções
17.
Parasitol Res ; 109(5): 1465-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21537985

RESUMO

Dactylogyrus intermedius is one of the most common and serious cause of parasitic diseases of freshwater fish in aquaculture, and can cause morbidity and high mortality in most species of freshwater fish worldwide. To attempt controlling this parasite and explore novel potential antiparasitic agents, the present study was designed to ascertain the anthelmintic activity of Chelidonium majus L. whole plant and to isolate and characterize the active constituents against D. intermedius. The ethanol extract from C. majus whole plant showed significant anthelmintic activity against D. intermedius [EC(50) (median effective concentration) value = 71.5 mg L(-1)] and therefore subjected to further isolation and purification using various chromatographic techniques. A quaternary benzo[c]phenanthridine alkaloid exhibited significant activity against D. intermedius was obtained and identified as chelidonine. In vivo anthelmintic efficacy tests exhibited that chelidonine was 100% effective against D. intermedius at a concentration of 0.9 mg L(-1), with EC(50) value of 0.48 mg L(-1) after 48 h of exposure, which is more effective than the positive control, mebendazole (EC(50) value = 1.3 mg L(-1)). In addition, the 48-h median lethal concentration (LC(50)) for chelidonine against the host (Carassius auratus) was 4.54 mg L(-1). The resulting therapeutic index for chelidonine was 9.46. These results provided evidence that chelidonine might be potential sources of new antiparasitic drugs for the control of Dactylogyrus.


Assuntos
Anti-Helmínticos/administração & dosagem , Benzofenantridinas/administração & dosagem , Infecções por Cestoides/tratamento farmacológico , Chelidonium/química , Doenças dos Peixes/tratamento farmacológico , Carpa Dourada/parasitologia , Platelmintos/efeitos dos fármacos , Animais , Anti-Helmínticos/isolamento & purificação , Benzofenantridinas/isolamento & purificação , Infecções por Cestoides/parasitologia , Cromatografia Líquida , Doenças dos Peixes/parasitologia , Extratos Vegetais/química , Platelmintos/isolamento & purificação
18.
J Renin Angiotensin Aldosterone Syst ; 11(4): 234-42, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20807796

RESUMO

INTRODUCTION: Angiotensin II (AngII) regulates blood pressure and water and electrolyte metabolism through the stimulation of NAD(P)H oxidase and production of reactive oxygen species (ROS) such as O2⁻, which is metabolised by superoxide dismutase, catalase and glutathione peroxidase. We assessed the role of AT1 and AT2 receptors, NAD(P)H oxidase and protein kinase C (PKC) in Ang II-induced sodium and water excretion and their capacity to stimulate antioxidant enzymes in the rat hypothalamus, a brain structure known to express a high density of AngII receptors. MATERIALS AND METHODS: Male Sprague-Dawley rats were intracerebroventricularly (ICV) injected with AngII and urinary sodium and water excretion was assessed. Urine sodium concentration was determined using flame photometry. After decapitation the hypothalamus was microdissected under stereomicroscopic control. Superoxide dismutase, catalase and glutathione peroxidase activity were determined spectrophotometrically and extracellular signal-regulated kinase (ERK1/2) activation was analysed by Western blot. RESULTS: AngII-ICV resulted in antidiuresis and natriuresis. ICV administration of losartan, PD123319, apocynin and chelerythrine blunted natriuresis. In hypothalamus, AngII increased catalase, superoxide dismutase and glutation peroxidase activity and ERK1/2 phosphorylation. These actions were prevented by losartan, apocynin and chelerythrine, and increased by PD123319. CONCLUSIONS: AT1 and AT2 receptors, NAD(P)H oxidase and PKC pathway are involved in the regulation of hydromineral metabolism and antioxidant enzyme activity induced by AngII.


Assuntos
Angiotensina II/farmacologia , Antioxidantes/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/enzimologia , NADPH Oxidases/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Animais , Benzofenantridinas/administração & dosagem , Benzofenantridinas/farmacologia , Catalase/metabolismo , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glutationa Peroxidase/metabolismo , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Injeções Intraventriculares , Losartan/administração & dosagem , Losartan/farmacologia , Masculino , Piridinas/administração & dosagem , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Sódio/urina , Superóxido Dismutase/metabolismo , Água
19.
Chem Biol Interact ; 188(3): 591-7, 2010 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-20691676

RESUMO

Several incidences of adverse effects on human health have been reported in many countries, due to consumption of edible oil adulterated with argemone oil (AO). The clinical manifestation of the disease is commonly referred to as epidemic dropsy. Our prior studies have shown that AO and isolated sanguinarine alkaloid (SANG) possess genotoxic and tumour initiating activity. In this study, the effect of AO/SANG was investigated on the development of tumour formation in mice using 7,12-dimethylbenz (a) anthracene (DMBA) initiated followed by tetradecanoyl phorbol acetate (TPA)-promoted skin tumour protocol. Single application of AO (300µl) or SANG (4.5µmol) when used during initiation phase in DMBA/TPA group did not reveal substantial difference in tumourigenic response. However, twice weekly application of AO (100µl) or SANG (1.5µmol) during promotion phase (25 weeks) resulted in enhanced tumourigenic response by ≥30% in DMBA/TPA treated group along with significant decrease in dermal tyrosinase (45-49%), histidase (30-32%), superoxide dismutase (53-56%), catalase (41%), GSH reductase (37-40%) and GSH-peroxidase activity (29-33%) compared to control. Furthermore, significant decrease of epidermal GSH (64-66%) content and enhanced formation of lipid peroxides (96-121%) was noticed following AO or SANG treatment during promotion phase to DMBA/TPA induced animals indicating the modified pro-oxidant status in skin. Although dermal biochemical parameters were also altered by AO or SANG when used during initiation phase in DMBA/TPA treated animals, nonetheless, the response in these parameters were relatively more when AO or SANG were used during promotion phase in DMBA/TPA treated animals. These results clearly suggest that AO and SANG have the ability to enhance the tumourigenic response, which may have relevance to its carcinogenic potential.


Assuntos
Benzofenantridinas/administração & dosagem , Benzofenantridinas/toxicidade , Isoquinolinas/administração & dosagem , Isoquinolinas/toxicidade , Óleos de Plantas/administração & dosagem , Óleos de Plantas/toxicidade , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia , Testes de Toxicidade/métodos , Administração Cutânea , Animais , Benzofenantridinas/isolamento & purificação , Modelos Animais de Doenças , Feminino , Humanos , Isoquinolinas/isolamento & purificação , Camundongos
20.
Zhongguo Zhong Yao Za Zhi ; 34(11): 1406-9, 2009 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19771873

RESUMO

OBJECTIVE: A high performance liquid chromatography (HPLC) method was developed to determine the concentration of nitidine chloride in plasma and successfully applied to study pharmacokinetics after i.v. administration in rabbits. METHOD: Twelve rabbits, randomized into 2 groups , were given i.v. at the dose of 4, 6 mg x kg(-1) respectively. Chloramphenicol was used as an internal standard. Nitidine chloride was extracted from plasma with ion pair reagent, and was determined by HPLC. RESULT: The calibration curves of nitidine chloride was linear in the range of 0.03-2.04 mg x L(-1). Its recoveries were more than 95%, intra-day and inter-day precisions were lower than 6%. The concentration-time curve of nitidine chloride in rabbits after i.v. of 4 and 6 mg x kg(-1) were shown to fit a two-compartment model, the main pharmacokinetic parameters showed no significant difference between the low and high dosage, and the AUC values are directly relative to doses. T1/2alpha were (5.46 +/- 0.89), (4.76 +/- 0.33) min respectively, T1/2beta were (263.33 +/- 16.4), (274.71 +/- 16.52) min respectively, AUC were (46.56 +/- 1.80), (69.19 +/- 2.30) microg x min(-1) x mL(-1) respectively. CONCLUSION: It is first time to establish the HPLC method to determine the concentration of nitidine chloride in rabbits plasma. The method is sensitive, accurate and reproducible. It is first time to study the pharmacokinetic characters of nitidine chloride in rabbits after i.v. administration, the elimination of nitidine chloride is linear pharmacokinetics.


Assuntos
Benzofenantridinas/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Benzofenantridinas/administração & dosagem , Benzofenantridinas/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Masculino , Coelhos , Distribuição Aleatória
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