RESUMO
Four novel and potently bioactive Amaryllidaceae alkaloids, 4,8-dimethoxy-cripowellin C (1), 4,8-dimethoxy-cripowellin D (2), 9-methoxy-cripowellin B (3), and 4-methoxy-8-hydroxy-cripowellin B (4), together with one known alkaloid, cripowellin C (5) were isolated from the 95% EtOH extract of the bulbs of Crinum latifolium. Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR as well as spectroscopy high resolution mass spectrometry. All isolates were in vitro evaluated for their cytotoxic activity against seven lung cancer cell lines, in addition to antimicrobial activity for eight bacteria, scavenging potential using ABTS·+ and DPPH test, and anti-inflammatory activity for Cox-1 and Cox-2 which had not previously been tested for crinane-type alkaloids with the cleavage between C-1 and C-13. Consequently, alkaloids 1-5 exhibited potent cytotoxicity against all of seven tested tumor cell lines with (IC50â¯<â¯30â¯nM). Alkaloids 3 and 4 displayed the significant antimicrobial activity with IC50 values <0.50â¯mM and antioxidant activity in the ABTS·+ and DPPH test. Additionally, Alkaloids 1-5 exhibited comparable inhibition of Cox-1 (>64%) and Cox-2 (>90%) with positive control.
Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Crinum/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/químicaRESUMO
We investigated the effects of arsenic trioxide (As(2)O(3)) as a possible approach for preventing airway remodeling in a murine model of bronchial asthma induced by ovalbumin (OVA) challenge. Forty Balb/c mice were randomly assigned to 1 of 4 groups (10 mice/group) as follows: controls (challenged with sterile saline inhalation only); OVA-challenged, no treatment; OVA-challenged, treated with dexamethasone; and OVA-challenged, treated with As(2)O(3). All mice were sensitized by intraperitoneal injection with 10% OVA at 2 weeks prior to saline or OVA inhalation challenge. Challenges were for 8 weeks. After OVA challenge, typical asthma-like morphology changes in the bronchi and lung tissues were observed by hematoxylin-eosin staining and pulmonary function indices were reduced compared with controls. Changes in pulmonary indices and lung tissues were similar in the dexamethasone and As(2)O(3) groups and were in between those of the untreated and control groups. Compared with the untreated group, transforming growth factor ß1, vascular endothelial growth factor, and matrix metalloproteinase-9 protein levels and mRNA expression were decreased in lung tissues of the dexamethasone and As(2)O(3) groups. Our results suggest that steroids and As(2)O(3) can inhibit airway remodeling in chronic asthma by mechanisms related to inhibiting the expression of the 3 aforementioned mediators.
Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Arsenicais/farmacologia , Asma/tratamento farmacológico , Brônquios/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Óxidos/farmacologia , Remodelação das Vias Aéreas/genética , Animais , Trióxido de Arsênio , Asma/genética , Asma/metabolismo , Asma/patologia , Brônquios/metabolismo , Brônquios/patologia , Dexametasona/farmacologia , Feminino , Pulmão/metabolismo , Pulmão/patologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Distribuição Aleatória , Testes de Função Respiratória/métodos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To investigate the expressions of and the effect of smoking on vascular endothelial growth factor (VEGF) and induced nitric oxide synthase (iNOS) in lung tissues of chronic obstructive pulmonary disease (COPD) patients. METHODS: The peripheral lung tissues were obtained from 46 patients with lung carcinoma. They were divided into three groups according to their habit of smoking and lung function, 19 smokers with moderate COPD, 12 smokers and 15 nonsmokers with normal lung function. The expression of VEGF and iNOS was detected by immunohistochemistry. RESULTS: Expressions of VEGF and iNOS were increased in lung tissues of smokers without COPD (1.50 +/- 0.39, 1.45 +/- 0.41) compared with nonsmokers without COPD (1.18 +/- 0.33, 1.09 +/- 0.41) (each P < 0.05), and were significantly increased in lung tissues of smokers with moderate COPD (2.19 +/- 0.51, 2.39 +/- 0.45) compared with nonsmokers without COPD (each P < 0.01). The expression of VEGF in lung tissues was significantly correlated with the expression of iNOS (r = 0.78, P < 0.01), but was inversely correlated with FEV(1) (r = -0.67, P < 0.01). CONCLUSIONS: Expressions of VEGF and iNOS were upregulated in lung tissues of smokers and patients with moderate COPD. Overexpression of iNOS and VEGF may participate in the mechanism of airway and vascular remodeling, and airflow limitation in COPD.
