RESUMO
The anti-inflammatory properties of soyasaponins (especially soyasaponins with different chemical structures) have scarcely been investigated. We investigated the inhibitory effects of five structural types of soyasaponins (soyasaponin A(1), A(2), I and soyasapogenol A, B) on the induction of nitric oxide (NO) and inducible NO synthase (iNOS) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Soyasaponin A(1), A(2) and I (25-200 µg/mL) dose-dependently inhibited the production of NO and tumor necrosis factor α (TNF-α) in LPS-activated macrophages, whereas soyasapogenol A and B did not. Furthermore, soyasaponin A(1), A(2) and I suppressed the iNOS enzyme activity and down-regulated the iNOS mRNA expression both in a dose-dependent manner. The reporter gene assay revealed that soyasaponin A(1), A(2) and I decreased LPS-induced nuclear factor kappa B (NF-κB) activity. Soyasaponin A(1), A(2) and I exhibit anti-inflammatory properties by suppressing NO production in LPS-stimulated RAW 264.7 cells through attenuation of NF-κB-mediated iNOS expression. It is proposed that the sugar chains present in the structures of soyasaponins are important for their anti-inflammatory activities. These results have important implication for using selected soyasaponins towards the development of effective chemopreventive and anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/química , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Saponinas/química , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Saponinas/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The aim of this study was to investigate the protective effects of andrographolide (AP), a bioactive component isolated from Andrographis paniculata, on carbon tetrachloride (CCl(4))-induced liver injury as well as the possible mechanisms involved in this protection in mice. Acute liver injury was induced by CCl(4) intoxication in mice. Serum biological analysis, lipid peroxides and antioxidant estimation, histopathological studies, reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay were carried out. CCl(4) treatment resulted in severe hepatic injury, as evidenced by significant elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and typical histopathological changes, such as hepatocyte necrosis. Additionally, CCl(4) administration led to oxidative stress in mice, as indicated by a remarkable increase in the hepatic malondialdehyde (MDA) level, together with a significant decrease in liver reduced glutathione (GSH) content. However, CCl(4)-induced hepatotoxicity was significantly attenuated by pretreatment with AP, as demonstrated by significant reduction of serum ALT, AST levels and hepatic MDA activity, along with a remarkable increase in hepatic GSH content. Histopathological changes induced by CCl(4) were also ameliorated by AP pretreatment. The marked increase of tumor necrosis factor-α (TNF-α) induced by CCl(4) was attenuated by AP, and the dramatic elevation of heme oxygenase-1 (HO-1) at transcriptional and protein levels was augmented following AP pretreatment. AP can effectively prevent liver injury induced by CCl(4), which may be due to inhibition of oxidative stress and inflammatory responses.
Assuntos
Andrographis/química , Antioxidantes/uso terapêutico , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Diterpenos/uso terapêutico , Fígado/efeitos dos fármacos , Fitoterapia , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Tetracloreto de Carbono , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Diterpenos/farmacologia , Glutationa/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Transcrição Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Early detection and precise diagnosis are critical for the patients with lung cancer. Increasing evidence has suggested that microRNAs (miRNAs) play important roles in the diagnosis of lung cancer. To evaluate the overall diagnostic performance of sputum miRNAs for the detection of lung cancer, a meta-analysis was performed. METHODS: A systematic search for published literature evaluating the diagnostic accuracy of sputum miRNAs in lung cancer was performed to determine pooled sensitivity and specificity. A summary receiver operating characteristic curve was constructed to assess the overall test performance. Subgroup analysis was utilized to explore potential sources of heterogeneity in the included studies. RESULTS: Eight studies with a total of 514 patients and 491 controls were included in this meta-analysis. Sputum miRNAs had a pooled sensitivity of 0.70 (95% confidence interval [95% CI]: 0.66-0.70) and a pooled specificity of 0.89 (95% CI: 0.86-0.91) for the detection of lung cancer, with an area under the summary receiver operating characteristics curve of 0.83. Significant interstudy heterogeneity for specificity was observed, with miRNA profiles being a possible source. CONCLUSION: Sputum miRNAs are potentially useful noninvasive markers for diagnosis of lung cancer. The diagnostic specificity of sputum miRNAs may be influenced by the miRNA profiles. It would be important for further work to evaluate the generalizability of our results by methodologically rigorous studies on a well-defined patient population.