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1.
Fitoterapia ; 137: 104285, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386897

RESUMO

Botanical-based natural products are an important resource for medicinal drug discovery and continue to provide diverse pharmacophores with therapeutic potential against cancer and other human diseases. A prototype Traditional Chinese Medicine (TCM) plant extract library has been established at the US National Cancer Institute, which contains both the organic and aqueous extracts of 132 authenticated medicinal plant species that collectively represent the potential therapeutic contents of most commonly used TCM herbal prescriptions. This library is publicly available in 96- and 384- well plates for high throughput screening across a broad array of biological targets, as well as in larger quantities for isolation of active chemical ingredients. Herein, we present the methodology used to generate the library and the preliminary assessment of the anti-proliferative activity of this crude extract library in NCI-60 human cancer cell lines screen. Particularly, we report the chemical profiling and metabolome comparison analysis of four commonly used TCM plants, namely Brucea javanica, Dioscorea nipponica, Cynanchum atratum, and Salvia miltiorrhiza. Bioassay-guided isolation resulted in the identification of the active compounds, and different extraction methods were compared for their abilities to extract cytotoxic compounds and to concentrate biologically active natural products.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/isolamento & purificação , Brucea/química , Linhagem Celular Tumoral , China , Cynanchum/química , Dioscorea/química , Descoberta de Drogas , Humanos , Medicina Tradicional Chinesa , National Cancer Institute (U.S.) , Compostos Fitoquímicos/isolamento & purificação , Salvia miltiorrhiza/química , Estados Unidos
2.
Fitoterapia ; 137: 104250, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271784

RESUMO

Obesity is associated with a number of metabolic disorders. Lipolysis is the initial step in the metabolism of lipids stored in adipocytes and is therefore considered a therapeutic target for obesity. Quassinoids are unique terpenes found in plants of the Simaroubaceae family, which were recently reported to have lipolytic activity and to suppress weight gain. Brucea javanica is a plant employed in traditional medicines in Asia, which is known to contain various quassinoids. Here, we investigated the lipolytic activity of B. javanica extracts, and identified six quassinoids: brucein A, brucein B, brucein C, 3'-hydroxybrucein A, brusatol, and bruceantinol, which represent the bioactive principals. The quassinoids contained in B. javanica demonstrated lipolytic activity at nanomolar concentrations, which were an order of magnitude lower than those of the previously reported quassinoids, suggesting that they may be useful for the treatment of obesity.


Assuntos
Adipócitos/efeitos dos fármacos , Brucea/química , Lipólise/efeitos dos fármacos , Quassinas/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Frutas/química , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Quassinas/isolamento & purificação , Sementes/química
3.
World J Gastroenterol ; 25(20): 2463-2472, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31171890

RESUMO

BACKGROUND: Esophageal cancer is one of the most common cancers around the world, and it has high incidence and mortality rates. The conventional therapy for esophageal cancer is radiotherapy, although its effect is highly limited by the resistance of esophageal cancer cells. Thus, strong radiosensitizers can be very crucial during radiotherapy against esophageal cancer. Brucea javanica oil emulsion (BJOE) is a widely used drug against various cancers, such as liver, colon, and ovarian cancer. However, its anti-cancer effect and mechanism and the use of BJOE as a radiosensitizer have not been explored in esophageal cancer. AIM: To evaluate the anti-cancer effect and mechanism of BJOE and explore the potential use of BJOE as a radiosensitizer during radiotherapy. METHODS: The inhibitory effect of BJOE and its enhancement function with radiation on cell viability were examined with the calculated half-maximal effective concentration and half-maximal lethal concentration. The influence of BJOE on cell migration and invasion were measured with EC109 and JAR cells by wound-healing and transwell assay. Clonogenesis and apoptotic rate, which was measured by Hoechst staining, were investigated to confirm its enhancement function with radiation. To investigate the molecular pathway underlying the effect of BJOE, the expressions of several apoptosis- and cycle-related proteins was detected by western blotting. RESULTS: Our results demonstrated that BJOE inhibited the growth of esophageal cancer cell lines more than normal cell lines, and it markedly reduced migration and invasion in esophageal cancer cells (EC109 and JAR). Moreover, it promoted cell apoptosis and enhanced the effect of radiotherapy against esophageal cancerous cells. In the viability test, the values of half-maximal effective concentration and half-maximal lethal concentration were reduced. Compared to the control, only around 1/5 colonies formed when using BJOE and radiation together in the clonogenic assay. The apoptotic rate in EC109 was obviously promoted when BJOE was added during radiotherapy. Our study suggests that the expression of the apoptosis-proteins Bax and p21 were increased, while the expression of Bcl-2 was stable. Further detection of downstream proteins revealed that the expression of cyclin D1 and cyclin-dependent kinase 4/6 were significantly decreased. CONCLUSION: BJOE has a strong anti-cancer effect on esophageal cancer and can be used as a radiosensitizer to promote apoptosis in cancerous esophageal cells via the cyclin D1-cyclin-dependent kinase 4/6 axis.


Assuntos
Brucea/química , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Óleos Vegetais/administração & dosagem , Radiossensibilizantes/administração & dosagem , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Emulsões , Neoplasias Esofágicas/patologia , Humanos , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
4.
Biomed Pharmacother ; 117: 109089, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226632

RESUMO

Bruceine D (BD) is the quassinoids isolated from the traditional Chinese herbal medicine Brucea javanica's fruit, which exhibits anti-cancer activity. Here, we demonstrated that BD inhibited human non-small cell lung cancer (NSCLC) cell lines in vitro that were attributed to the induction of cell apoptosis. Human NSCLC H460 and A549 cell lines were treated with BD, and cell viability was conducted with CCK-8 assay. Cell clone formation was observed by clone formation assay. Cell apoptosis was measured using DAPI staining and flow cytometry. Protein levels was analyzed by western blot. The results showed BD inhibited the cell viability of H460 and A549 cells in a dose-dependent manner with IC50 values of 0.5 and 0.6 µmol/L, respectively, at 48 h of treatment. Treatment with BD (0.125-1.0 µmol/L) dose-dependently promoted chromatin condensation, Annexin V-positive cell population and caspase-dependent apoptosis in H460 and A549 cells. Mechanistically, BD stimulated the phosphorylation of JNK. Furthermore, the anti-cancer effects of BD were alleviated effectively by a specific JNK inhibitor SP600125 in NSCLC cells. In conclusion, the results demonstrated that BD exerted anti-cancer activity against NSCLC cells through JNK activation, which suggests its potent usefulness for prevention and treatment of NSCLC.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quassinas/farmacologia , Células A549 , Antineoplásicos Fitogênicos/farmacologia , Brucea/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Fosforilação/efeitos dos fármacos
5.
J Agric Food Chem ; 67(15): 4232-4239, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30901209

RESUMO

Systemicity is a desirable property for insecticides. Many phytochemicals show good systemic properties and thus are natural sources of novel systemic insecticidal ingredients. Bruceine D, a quassinoid, was identified in Brucea javanica (L.) Merr. and displayed outstanding systemic properties and excellent antifeedant activity against the diamondback moth (DBM, Plutella xylostella L.), beet armyworm ( Spodoptera exigua Hübner), and cotton leafworm ( Spodoptera litura Fabricius). Its antifeedant effect on third instar larvae of DBM was approximately 6.2-fold stronger than that of azadirachtin. When bruceine D was applied to roots at a concentration of 100 µg/mL for 24 and 48 h, its concentration in flowering Chinese cabbage ( Brassica campestris L. ssp. chinensis var. utiliz Tsen et Lee) leaves was 38.69 µg/g (fresh weight, FW) and 108.45 µg/g (FW), respectively. These concentrations could achieve 93.80% and 96.83% antifeedant effects, which were significantly greater than those of azadirachtin. Similar to azadirachtin, bruceine D also posed a potent growth inhibition effect on insect larvae. After feeding with 20 µg/g bruceine D, no pupae were observed. The results demonstrated that bruceine D is an effective botanical insect antifeedant with outstanding systemic properties, causing potent pest growth inhibitory activity.


Assuntos
Brucea/química , Comportamento Alimentar/efeitos dos fármacos , Inseticidas/farmacologia , Lepidópteros/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Brassica/parasitologia , Inseticidas/química , Inseticidas/isolamento & purificação , Lepidópteros/crescimento & desenvolvimento , Lepidópteros/fisiologia , Controle Biológico de Vetores , Doenças das Plantas/parasitologia , Doenças das Plantas/prevenção & controle , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Pupa/efeitos dos fármacos , Pupa/crescimento & desenvolvimento
6.
Biomed Pharmacother ; 114: 108766, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901719

RESUMO

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.


Assuntos
Brucea/química , Doença de Crohn/tratamento farmacológico , Emulsões/farmacologia , NF-kappa B/metabolismo , Óleos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Colo/efeitos dos fármacos , Colo/metabolismo , Doença de Crohn/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley
7.
Int J Med Sci ; 15(13): 1517-1521, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30443173

RESUMO

The present study aimed to investigate the effects of ethanol extract from Brucea javanicaseed (EEBJS) on the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the possible molecular signal involved. Firstly, a Matrigel-based in vitro angiogenesis assay demonstrated that EEBJS inhibited the angiogenesis of HUVECs in a dose-dependent manner. Then by using porcine aortic endothelial cells which stably express human PDGFR-beta, we found that the inhibition of angiogenesis was mediated by PDGFR-beta. Taken together, we conclude that EEBJS inhibited the angiogenesis function of the vascular endothelial cells mediated by PDGFR-beta, and postulate that it might contribute to the therapeutic effects of EEBJS on malignant tumors.


Assuntos
Brucea/química , Etanol/química , Neovascularização Fisiológica/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Sementes/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Transdução de Sinais/efeitos dos fármacos
8.
Biomed Pharmacother ; 106: 403-410, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29966986

RESUMO

Since 1970, the isolated and identified components of Brucea javanica (L.) Merr. have been known to contain anticancer effects, particularly antileukemic effect. In this study, the inhibitory effect of Brucea javanica (BJ) on cell growth and inflammation was confirmed in human T-cell acute lymphocytic leukemia (T-ALL) cells, and its efficacy as an antileukemic agent was verified. Our results showed that BJ extract induced caspase-dependent apoptosis of T-ALL Jurkat cells through inhibition of the CK2-mediated signaling pathway, while exerting no significant cytotoxicity in normal peripheral blood mononuclear cells. Moreover, BJ extract suppressed the NF-κB signaling pathway, thus, inhibiting the interleukin (IL)-2 expression induced by phorbol 12-myristate 13-acetate (PMA) and phytohemagglutinin (PHA). Notably, combined treatment with BJ extract plus CX-4945 or imatinib exerted enhanced inhibitory effects on T-ALL cell growth and IL-2 production. Overall, these results suggest that BJ extract can be a potent therapeutic herbal agent for T-ALL treatment and prevention of IL-2 mediated inflammatory immune responses.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Brucea , Proliferação de Células/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Imunossupressores/farmacologia , Naftiridinas/farmacologia , Extratos Vegetais/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Apoptose/efeitos dos fármacos , Brucea/química , Caseína Quinase II/metabolismo , Caspase 3/metabolismo , Caspase 8/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Imunossupressores/isolamento & purificação , Interleucina-2/metabolismo , Células Jurkat , NF-kappa B/metabolismo , Fosforilação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
9.
Drug Des Devel Ther ; 12: 657-671, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29636600

RESUMO

Background: Brucea javanica (L.) Merr. is a plant from the genus Brucea, which is used in local traditional medicine to treat various diseases. Recent studies revealed an impressive anticancer efficiency of B. javanica extract in different types of cancer cells. Purpose: In this study, we have investigated the cytotoxic effects of the B. javanica hexane, ethanolic extracts against colon cancer cells. HT29 colon cells were selected as an in vitro cancer model to evaluate the anticancer activity of B. javanica ethanolic extract (BJEE) and the possible mechanisms of action that induced apoptosis. Methods: 3-(4,5-dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, acridine orange/propidium iodide, and annexin-V-fluorescein isothiocyanate assays were performed to determine the antiproliferative and apoptosis validation of BJEE on cancer cells. Measurement of reactive oxygen species (ROS) production, caspase activities, nucleus factor-κB activity, and gene expression experiments was done to investigate the potential mechanisms of action in the apoptotic process. Results: The results obtained from this study illustrated the significant antiproliferative effect of BJEE on colorectal cancer cells, with a concentration value that inhibits 50% of the cell growth of 25±3.1 µg/mL after 72 h of treatment. MTT assay demonstrated that the BJEE is selectively toxic to cancer cells, and BJEE induced cell apoptosis via activation of caspase-8 along with modulation of apoptosis-related proteins such as Fas, CD40, tumor necrosis factor-related apoptosis-inducing ligands, and tumor necrosis factor receptors, which confirmed the contribution of extrinsic pathway. Meanwhile, increased ROS production in treated cells subsequently activated caspase-9 production, which triggered the intrinsic pathways. In addition, overexpression of cytochrome-c, Bax, and Bad proteins along with suppression of Bcl-2 illustrated that mitochondrial-dependent pathway also contributed to BJEE-induced cell death. Consistent with the findings from this study, BJEE-induced cancer cell death proceeds via extrinsic and intrinsic mitochondrial-dependent and -independent events. Conclusion: From the evidence obtained from this study, it is concluded that the BJEE is a promising natural extract to combat colorectal cancer cells (HT29 cells) via induction of apoptosis through activation of extrinsic and intrinsic pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Brucea/química , Frutas/química , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Proteína Supressora de Tumor p53/biossíntese , Regulação para Cima , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Regulação para Cima/efeitos dos fármacos
10.
BMC Cancer ; 18(1): 411, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29649989

RESUMO

BACKGROUND: Brucea javanica oil emulsion (BJOE) is traditional Chinese medicine with implicated anti-tumor activity, which has been used for treating lung cancer in China. The aim of this investigation was to evaluate the effects and safety of intrapleural injection of BJOE in treating malignant pleural effusion (MPE). METHODS: The randomised controlled trials (RCTs) on the effects and safety of BJOE in treating MPE were searched from electronic medical database including MEDLINE, SCI, EMBASE, Cochrance Library and CNKI. A total of 14 RCTs with 1085 patients were involved in this meta-analysis. RESULTS: The overall response rate (ORR) of traditional chemotherapy drugs plus BJOE was higher than that of traditional chemotherapy drugs alone (p = 0.001; odds ratio = 1.39). Meanwhile, the combination of BJOE and traditional chemotherapy drugs improved the quality of life (QOL) of patients with MPE (p < 0.001; odds ratio = 1.56) compared with traditional chemotherapy drugs alone. Moreover, the participation of BJOE reduced the myelotoxicity and digestive reactions caused by traditional chemotherapy drugs (p < 0.05). CONCLUSIONS: The efficacy and safety of traditional chemotherapy drugs plus BJOE was superior to traditional chemotherapy drugs alone via intrapleural injection in controlling MPE, which suggested that BJOE can be used to treat MPE.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Brucea/química , Óleos Vegetais/administração & dosagem , Óleos Vegetais/química , Derrame Pleural Maligno/tratamento farmacológico , Emulsões , Humanos , Razão de Chances , Perfusão , Derrame Pleural Maligno/patologia , Viés de Publicação , Qualidade de Vida , Resultado do Tratamento
11.
Chin J Nat Med ; 16(4): 293-301, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29703329

RESUMO

In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box-Behnken design consisted of 1.7% alginate (W/V), 1.02% carrageenan (W/V), 1.4% CaCO3 (W/V), and a gelling bath of pH 0.8. The alginate-carrageenan-Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%-55% and an encapsulation efficiency of 70%-80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention (> 60% at 6 h) in fasted rats, compared to non-floating beads (15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography (SPET/CT). In conclusion, the alginate-carrageenan-Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.


Assuntos
Alginatos/química , Brucea/química , Preparações de Ação Retardada/química , Mucosa Gástrica/metabolismo , Microesferas , Óleos Vegetais/química , Animais , Disponibilidade Biológica , Carragenina/química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Óleos Vegetais/administração & dosagem , Óleos Vegetais/farmacocinética , Ratos , Ratos Sprague-Dawley
12.
Drug Des Devel Ther ; 12: 535-544, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29559770

RESUMO

Background: Brucea javanica oil (BJO), a traditional Chinese herbal medicine, has a variety of pharmacological activities and several BJO-related patent drugs have been widely used in China. Purpose: The objective of this study was to evaluate the gastric therapeutic effects of self-made BJO and its pharmaceutical potential to formulate novel BJO gastroretentive floating bead by comparing with commercial products. Methods: BJO was extracted from the seeds of B. javanica, and its therapeutic effects were evaluated by comparing with commercial products in the treatment of human gastric cancer and gastric ulcer. Furthermore, the developed gastroretentive drug delivery system was evaluated by in vivo tests. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the concentration of glycerol trioleate in the pharma-cokinetic study was applied. Results: The antitumor activity of BJO was stronger than that of the marketed preparation; the 50% inhibitory concentration (IC50) values of BJO extracts on HGC27, SGC7901 and BGC823 gastric carcinoma were 0.3091, 1.736 and 2.743 µg/mL, respectively, whereas the values of marked BJO preparation were 15.26, 32.60 and 7.456 µg/mL, respectively. Histopathological studies demonstrated the ability of BJO to locally prevent and treat absolute ethanol-induced gastric ulcer. Developed BJO gastroretentive floating bead showed a satisfactory in vivo study. The highest glycerol trioleate concentration in the stomach after taking BJO gastroretentive floating bead was nearly two times higher when compared to the marketed BJO soft capsule. Conclusion: Self-made BJO has a strong therapeutic effect on the stomach, and gastroretentive drug delivery system can be a promising approach to prolong and enhance its therapy ability when treating gastric diseases.


Assuntos
Brucea/química , Sistemas de Liberação de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Óleos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Medicina Tradicional Chinesa , Estrutura Molecular , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Sementes/química , Úlcera Gástrica/patologia , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem , Trioleína/análise , Células Tumorais Cultivadas
13.
J Ethnopharmacol ; 215: 21-26, 2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29288829

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Brucea javanica and its aqueous decoction is a traditional medicine consumed by diabetic patients in Malaysia. The daily consumption of B. javanica seeds and it's aqueous decoction causes much concern as the quassinoids and its glycosides from the seeds exhibited various pharmacological activity at low doses. AIMS OF STUDY: The aim of the present study is to evaluate the repeated dose toxicity of the standardized aqueous extract administered daily for 30 days through oral administration at its effective hypoglycemia doses. MATERIALS AND METHODS: The seeds were dried, ground and extracted in deionized water. A HPLC-photodiode array method was developed and validated for the standardization of both the hypoglycemia agents, namely bruceine D and E in aqueous extract. Both normoglycemia and streptozotocin (STZ)-induced diabetic rats were fed orally with 15, 30 and 60mg/kg body weight of standardized aqueous extract. The blood glucose was measured at 0-8h. In repeated dose toxicity, similar doses were administered orally to rats for 30 days. At the end of 30 days, the blood was withdrawn and subjected to biochemical and haematology analysis while organs were harvested for histology analysis. RESULTS: Oral administration of standardized aqueous extract exhibited a dose-response relationship in both the normoglycemia and STZ-induced diabetic rats. Daily oral administration of 15, 30 and 60mg/kg standardized aqueous extract for 30 days to rats did not show signs to toxicity in its biochemical, haematology and histology analysis. CONCLUSION: In conclusion, although the seeds were reported to contain compounds with various pharmacological activity, the daily oral administration to rats for 30 days do not showed signs of toxicity at its effective hypoglycemia doses.


Assuntos
Brucea/química , Extratos Vegetais/efeitos adversos , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade
14.
J Drug Target ; 26(3): 222-230, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28701059

RESUMO

This study was conducted to evaluate the efficacy and possible mechanism of Brucea javanica oil emulsion (BJOE) on cachexia, by observing changes in related indexes in mice with cachexia and identifying the genes responsible based on gene chip analysis. In the BJOE treatment group, body weight loss, tumour growth and metastasis were found obviously inhibited, food and water intake had markedly increased, and survival time was significantly prolonged, as compared to the control group. Moreover, the BJOE witnessed improvement in body weight, prevention of tumour metastasis and overall increase in survival time, as compared to Indometacin (IND, the positive control medicine). It was also found that TNF-α and IL-6 in serum were significantly lower in both groups of BJOE and IND, than in the control group (p < .01). Based on the gene expression data, seven and six hub genes of BJOE and IND groups were found in the potential prognostic impacts networks, and three common genes comprising of Nmd3, Bcl2 and Nhp2l1 were screened. Thus, BJOE could reduce tumour growth and effectively alleviate cancer cachexia, due to inhibition of pro-inflammatory cytokines. Nmd3, Bcl2, Nhp2l1 may be important drug targets, establishing the role of BJOE in the treatment of lung cancer induced cachexia.


Assuntos
Brucea/química , Caquexia/tratamento farmacológico , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Óleos Vegetais/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Caquexia/etiologia , Caquexia/metabolismo , Caquexia/patologia , Carcinoma Pulmonar de Lewis/patologia , Ingestão de Alimentos/efeitos dos fármacos , Emulsões/química , Emulsões/farmacologia , Interleucina-6/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óleos Vegetais/química , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Proteínas de Ligação a RNA/sangue , Distribuição Aleatória , Ribonucleoproteínas Nucleares Pequenas/sangue , Fator de Necrose Tumoral alfa/sangue
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(11): 1202-1208, 2018 Nov 28.
Artigo em Chinês | MEDLINE | ID: mdl-30643064

RESUMO

OBJECTIVE: To investigate the effect of Brucea javanica oil emulsion on proliferation, migration and autophagy of non-small cell lung cancer A549 cells.
 Methods: First, A549 cells were divided into a control group and a low, medium or high dose of Brucea javanica oil emulsion groups (0, 2.5, 5.0 or 10.0 mg/mL); then, the cells were divided into a 3-MA+Brucea javanica oil emulsion group and a Brucea javanica oil emulsion group in the presence or absence of 3-methyl adenine (3-MA). Cell counting kit-8 (CCK-8) and clone formation assay were used to detect cell proliferation, while the wound scratch and Transwell assay were used to measure cell migration. Cell immunofluorescence and Western blot were used to analyze autophagy.
 Results: Compared with the control group, the numbers of cell proliferation and colony-formation, the relative cell migration rate and numbers of trans-membrane cells were reduced in a dose-dependent manner in the Brucea javanica oil emulsion groups (all P<0.05). Meanwhile, compared with the control group, the aggregation of microtubule associated protein 1 light chain3 (LC3) green fluorescence and the LC3-II/LC3-I ratios were increased, while p62 level was decreased (all P<0.05) in the high dose group. Compared with the Brucea javanica oil emulsion group (5.0 mg/mL), the cell proliferation, numbers of cell clone formation, cell migration rate and numbers of Transwell transmembrane cells were increased in the 3-MA+Brucea javanica oil emulsion group (all P<0.05).
 Conclusion: Brucea javanica oil emulsion can promote the autophagy of non-small cell lung cancer A549 cells and inhibit the cell proliferation and migration.


Assuntos
Autofagia/efeitos dos fármacos , Brucea , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Óleos Vegetais , Células A549 , Brucea/química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Óleos Vegetais/farmacologia
16.
Curr Pharm Biotechnol ; 18(10): 855-861, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29231135

RESUMO

BACKGROUND: The novel water-soluble inclusion complex of Brucea javanica oil (BJO) by ß-cyclodextrin polymers (CDP) was prepared by saturated aqueous method and characterized by SEM, FT-IR and 1H NMR. Compared with BJO, the aqueous solubility of BJO-CDP (77.76%) greatly enhanced due to the water-soluble CDP host. RESULTS: In the acute toxicity test, the value of LD50 of BJO-CDP was 11.94 g/kg, suggesting the lower toxicity of BJO-CDP. Moreover, the pharmacodynamics of BJO-CDP was investigated by evaluating its inhibition effects on human hepatoma SMMC-7721 cells and mice transplantable colon cancer CT- 26 cells. CONCLUSION: It has been revealed that BJO-CDP significantly decreased the toxicity of BJO and enhanced its anti-tumor activity. In conclusion, BJO-CDP could be a new and improved clinical formulation of BJO with higher water solubility, lower toxicity and enhanced anti-tumor activity.


Assuntos
Apoptose/efeitos dos fármacos , Brucea/química , Óleos Vegetais , beta-Ciclodextrinas/química , Animais , Linhagem Celular Tumoral , Humanos , Dose Letal Mediana , Camundongos , Camundongos Endogâmicos ICR , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/farmacologia , Óleos Vegetais/toxicidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Testes de Toxicidade Aguda
17.
J BUON ; 22(4): 985-995, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28952218

RESUMO

PURPOSE: To assess the effectiveness and safety of javanica oil emulsion injection (JOEI) when combined with radiotherapy (RT) in patients with esophageal cancer. METHODS: Electronic databases including EMBASE, PUBMED, the COCHRANE Library, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, and Chinese Scientific Journals Database were searched. Two reviewers performed the search, identified and extracted eligible studies. Items including response rate, survival and safety were extracted and analyzed using Review Manager 5.3. RESULTS: A total of 16 clinical studies with 1269 esophageal cancer patients were included. The results showed that adding JOEI to RT could improve the complete response (CR rate) (Odds Ratio/OR 1.63; 95% confidence interval (CI), 1.27 to 2.10; p=0.0001), partial response (PR) (OR 1.25; 95% CI, 0.97 to 1.60; p=0.09), Relative Risk/RR (OR 1.42; 95% CI, 1.19 to 1.70; p<0.0001), quality of life (OR 3.01; 95% CI, 1.72 to 5.25; p=0.0001), and reduce the incidence of adverse events including nausea and vomiting (OR 0.81; 95% CI, 0.45 to 1.44; p=0.46) and radiation esophagitis (OR 0.47; 95% CI, 0.33 to 0.68; p<0.0001). The 1-, 2-, and 3-year survival rates in the JOEI group were significantly higher than those in the RT alone group (p<0.001). CONCLUSIONS: JOEI in combination with RT could benefit esophageal cancer patients with improved rate of response and quality of life, prolonged survival, and reduced incidence of adverse events. However, these results should be viewed with caution due to the limited quality of the included studies.


Assuntos
Brucea/química , Emulsões/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Óleos Vegetais/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
18.
J Nat Prod ; 80(8): 2384-2388, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28731697

RESUMO

The first total synthesis of the natural product bruceolline I, isolated in small quantities from the ethanol extract of Brucea mollis stems, was achieved in 29% yield over nine steps and with high enantiomeric purity (>98%). The key step of the process is the tandem gold-catalyzed rearrangement/Nazarov reaction of a propargylic acetate derivative. This synthesis provides a sufficient amount of synthesized bruceolline I for further bioassays.


Assuntos
Brucea/química , Ciclopentanos/síntese química , Indóis/síntese química , Caules de Planta/química , Produtos Biológicos , Catálise , Ciclopentanos/química , Ciclopentanos/isolamento & purificação , Indóis/química , Indóis/isolamento & purificação , Estrutura Molecular , Estereoisomerismo
19.
Molecules ; 22(6)2017 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-28587214

RESUMO

Our research aimed to optimize the oil extraction process and determine the fatty acids in Brucea javanica (L.) Merr. seeds. The extraction technology was optimized using response surface methodology. A Box-Behnken design was employed to investigate the effects of three independent variables on an ultrasonic-assisted extraction technique, namely, sonication time (X1: 20-40 min), liquid-solid ratio (X2: 16:1 mL/g-24:1 mL/g), and ethanol concentration (X3: 90%-100%). The optimum conditions of sonication time, liquid-solid ratio, and ethanol concentration were 40 min, 24:1 mL/g, and 100%, respectively. The content of fatty acids and the oil yield were 14.64 mg/g and 16.87%, respectively, which match well with the predicted models. The optimum number of extraction times was eventually identified as two. A new rapid method for the qualitative and quantitative analysis of the fatty acids of B. javanica (L.) Merr. seed oil using HPLC with a charged aerosol detector was described. The fatty acid contents of 14 batches of B. javanica (L.) Merr. seed oil were determined, and the relevance and difference were analyzed by fingerprint analysis. The fingerprint has five common peaks, and the similarity was greater than 0.991. HPLC analysis represents a specialized and rational approach for the quality identification and comprehensive evaluation of B. javanica (L.) Merr. seed oils.


Assuntos
Brucea/química , Ácidos Graxos/análise , Óleos Vegetais/química , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos/química , Sementes/química , Sonicação
20.
Artigo em Inglês | MEDLINE | ID: mdl-28407533

RESUMO

OBJECTIVES: The quassinoid brusatol, which can be isolated from Brucea javanica (L.) Merr., becomes popularly studied because of its anti-tumor activity. In order to further investigate brusatol and extend its applications, a sensitive analytical method for determination of brusatol in biological samples is essential. However, few methods had been reported until now. In this study, a highly sensitive and reproducible LC-MS method for simultaneous quantification of brusatol in mouse plasma and tissues was developed and validated. METHOD: Plasma samples and tissue homogenate were extracted with diethyl ether after addition of the internal standard solution(IS). The supernatant was blown to dryness with nitrogen and residual was reconstituted with 100µl of methanol. The separation was performed on an Intersil ODS-3 column and gradient elution was conducted with the mobile phase of water and methanol (0-5min 47:53, 5-5.5min 47:53-10:90, 5.5-9min 10:90, posttime 4min 47:53) at a flow rate of 0.8mL/min. Quantification was performed in the selected ion monitoring (SIM) mode at m/z 543.2 for brusatol and 220.0 for IS (ornidazole). The method was validated by analyzing quality control plasma and tissue homogenate samples, and was applied to analyze samples obtained from mice after injections of brusatol via the tail vein. RESULTS: With ornidazole as the internal standard, calibration curve of the method ranged from 10 to 320ng/ml for plasma and 10-240ng/ml for tissues. Recovery rate of brusatol from plasma and tissues were between 71.09%-94.91%. Relative standard deviation (RSD) for inter- and intra-day precision was less than 15%, and the accuracy was between 96.1%-111.8%. The pharmacokinetics and distribution study of brusatol in mice after three single doses via the tail vein were carried out based on this method. The concentration of brusatol in plasma decreased rapidly and a more than 10 fold concentration of brusatol was found as compared to that in other tissues. CONCLUSIONS: This is the first reported LC-MS method for detecting brusatol in tissues and can accurately determine the concentrations of these compounds in plasma and different tissues. Further research on the metabolism of brusatol in vivo is still needed.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Quassinas/farmacocinética , Animais , Antineoplásicos Fitogênicos/sangue , Antineoplásicos Fitogênicos/química , Brucea/química , Feminino , Limite de Detecção , Masculino , Camundongos , Quassinas/sangue , Quassinas/química , Distribuição Tecidual
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