Molecular characterization and comparative analysis of pandemic H1N1/2009 strains with co-circulating seasonal H1N1/2009 strains from eastern India.

During the peak outbreak (July-September 2009), a total 1886 patients were screened in eastern India, of which 139 (7.37%) and 52 (2.76%) were positive for pH1N1 and seasonal H1N1, respectively. Full-length HA1, NA, NS1 and PB1-F2 genes of representative strains were sequenced. Phylogenetic analysis of deduced amino acid sequences of pH1N1 strains revealed HA1 and NS1 to be of North American swine lineage, and the NA gene of Eurasian swine lineage. Consistent with previous reports, the PB1-F2 gene of pH1N1 strains was unique due to a mutation resulting in a truncated protein of 11 aa. The HA, NA and NS1 genes of H1N1/2009 strains clustered with H1N1 strains of 2000-2009, whereas a subset of strains contained a pH1N1-like truncated PB1-F2. The truncated PB1-F2 may confer the advantage of lower pathogenicity but higher replication and infectivity to the human H1N1 strains. This is the first report of seasonal H1N1/2009 strains with a pH1N1/2009-like gene segment.

Protective effect of coconut water concentrate and its active component shikimic acid against hydroperoxide mediated oxidative stress through suppression of NF-κB and activation of Nrf2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Conventionally coconut water has been used as an 'excellent hydrating' drink that maintain the electrolyte balance and help in treating diverse ailments related to oxidative stress including liver function. The present study was aimed to elucidate whether and how the coconut water concentrate (CWC) and its major active phytoconstituent shikimic acid (SA) can effectively protect murine hepatocytes from the deleterious effect of hydroperoxide-mediated oxidative stress. MATERIALS AND METHODS: Bioactivity guided fractionation of CWC resulted in the isolation of a couple of known compounds. Freshly isolated murine hepatocytes were exposed to hydrogen peroxide (H2O2) (1 and 3mM) in the presence or absence of CWC (200 and 400 µg/ml) and SA (40 µM) for the determination of antioxidative, DNA protective, cellular ROS level by modern methods, including immunoblot and flowcytometry to find out the possible mechanism of action. RESULTS: Pre-treatment of hepatocyte with CWC and SA showed significant prevention of H2O2-induced intracellular ROS generation, nuclear DNA damage along with the formation of hepatic TBARS and cellular nitrite. Further, the H2O2 induced cell death was arrested in the presence of CWC through the inhibition of CDC42 mediated SAPK/JNK pathways and activation of other molecules of apoptotic pathways, including Bax and caspase3. Moreover, CWC and SA help in maintaining the GSH level and endogenous antioxidants like Mn-SOD, to support intracellular defense mechanisms, probably through the transcriptional activation of Nrf2; and inhibition of nuclear translocation of NF-κB. CONCLUSION: CWC and its active components SA reversed the H2O2 induced oxidative damage in hepatocytes, probably through the inhibition of NF-κB, with the activation of PI3K/Akt/Nrf2 pathway and reduction of apoptosis by interfering the SAPK/JNK/Bax pathway.

Recent advancements for the evaluation of anti-viral activities of natural products.

Significant progress has been achieved for the development of novel anti-viral drugs in the recent years. Large numbers of these newly developed drugs belong to three groups of compounds, nucleoside analogues, thymidine kinase-dependent nucleotide analogues and specific viral enzyme inhibitors. It has been found that the natural products, like plant extract, plant-derived compounds (phytochemicals) and so on, as well as traditional medicines, like Ayurvedic, traditional Chinese medicine (TCM), Chakma medicines and so on, are the potential sources for potential and novel anti-viral drugs based on different in vitro and in vivo approaches. In this chapter some of these important approaches utilised in the drug discovery process of potential candidate(s) for anti-viral agents are being discussed. The key conclusion is that natural products are one of the most important sources of novel anti-viral agents.