3,4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A Virus.

Brazilian green propolis water extract (PWE) and its chemical components, caffeoylquinic acids, such as 3,4-dicaffeoylquinic acid (3,4-diCQA), act against the influenza A virus (IAV) without influencing the viral components. Here, we evaluated the anti-IAV activities of these compounds in vivo. PWE or PEE (Brazilian green propolis ethanol extract) at a dose of 200 mg/kg was orally administered to Balb/c mice that had been inoculated with IAV strain A/WSN/33. The lifetimes of the PWE-treated mice were significantly extended compared to the untreated mice. Moreover, oral administration of 3,4-diCQA, a constituent of PWE, at a dose of 50 mg/kg had a stronger effect than PWE itself. We found that the amount of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA in the mice that were administered 3,4-diCQA was significantly increased compared to the control group, while H1N1 hemagglutinin (HA) mRNA was slightly decreased. These data indicate that PWE, PEE or 3,4-diCQA possesses a novel and unique mechanism of anti-influenza viral activity, that is, enhancing viral clearance by increasing TRAIL.

Caffeoylquinic acids are major constituents with potent anti-influenza effects in brazilian green propolis water extract.

Influenza A viral infections reached pandemic levels in 1918, 1957, 1968, and, most recently, in 2009 with the emergence of the swine-origin H1N1 influenza virus. The development of novel therapeutics or prophylactics for influenza virus infection is urgently needed. We examined the evaluation of the anti-influenza virus (A/WSN/33 (H1N1)) activity of Brazilian green propolis water extract (PWE) and its constituents by cell viability and real-time PCR assays. Our findings showed strong evidence that PWE has an anti-influenza effect and demonstrate that caffeoylquinic acids are the active anti-influenza components of PWE. Furthermore, we have found that the amount of viral RNA per cell remained unchanged even in the presence of PWE, suggesting that PWE has no direct impact on the influenza virus but may have a cytoprotective activity by affecting internal cellular process. These findings indicate that caffeoylquinic acids are the active anti-influenza components of PWE. Above findings might facilitate the prophylactic application of natural products and the realization of novel anti-influenza drugs based on caffeoylquinic acids, as well as further the understanding of cytoprotective intracellular mechanisms in influenza virus-infected cells.

Monitoring of Blood Vessel Density Using Contrast-Enhanced High Frequency Ultrasound May Facilitate Early Diagnosis of Lymph Node Metastasis.

Time-dependent alterations in the ultrasonography characteristics of lymph nodes during early-stage metastasis have not been compared with those of tumor-draining lymph nodes that do not develop tumor; this is partly due to the absence of an appropriate experimental model. In a previous study of lymph nodes with experimental early-stage metastasis, we used contrast-enhanced high-frequency ultrasound to demonstrate that an increase in lymph node blood vessel density preceded any changes in lymph node volume. In the present study, we used an experimental model of lymph node metastasis in which tumor cells metastasized from the subiliac lymph node to the proper axillary lymph node (the tumor-draining lymph node). We utilized contrast-enhanced high-frequency ultrasound to perform a longitudinal analysis of tumor-draining lymph nodes, comparing those at an early-stage of metastasis with those that did not develop detectable metastasis. We found that the normalized blood vessel density of an early-stage metastatic lymph node exhibited a progressive rise, whereas that of a tumor-draining lymph node not containing tumor began to increase later. For both types of lymph nodes, the normalized blood vessel density on the final day of experiments showed a trend towards being higher than that measured in controls. We further found that mice with an initially low value for lymph node blood vessel density subsequently showed a larger increase in the blood vessel density of the metastatic lymph node; this differed significantly from measurements in controls. The present study indicates that a longitudinal analysis of the blood vessel densities of tumor-draining lymph nodes, made using contrast-enhanced high-frequency ultrasound imaging, may be a potentially promising method for detecting early-stage lymph node metastasis in selected patients. Furthermore, our findings suggest that tumor in an upstream lymph node may induce alteration of the vascular structures in draining lymph nodes that do not contain tumor.