Potential Use of Euphorbia hirta

Euphorbia hirta commonly known as Tawa-Tawa is a plant used in folklore medicine in the Philippines for the treatment of dengue. Though, E. hirta has been extensively investigated for numerous bioactivities, limited studies have been conducted on the antidengue activity. Thus, the present study provides a comprehensive review of studies conducted on the antidengue activity of E. hirta. A systematic literature survey was carried out in scientific databases, PubMed®, Scopus, and Google Scholar, for research carried on the antidengue activity of E. hirta. The literature search identified a total of 867 articles: databases PubMed = 6, Scopus SciVerse® = 423, and Google Scholar = 437; one additional article was identified by searching reference lists. Eight full papers were entitled to the review; out of those, two studies focused on ethnobotanical surveys, three on animal experiments, one on human trial, and two on in vitro antiviral activities, and one was computational study. The available evidence conclusively demonstrates the potential of E. hirta against dengue as it holds significant antiviral and platelet increasing activities. However, the number of studies conducted to validate its antidengue activity was found to be inadequate. Hence, well-controlled clinical trials and contemporary pharmacological approaches including activity guided fractionation and elucidation of the mode of action are encouraged to establish the use of E. hirta for dengue

Zebrafish Embryo Toxicity of a Binary Mixture of Pyrethroid Insecticides: d-Tetramethrin and Cyphenothrin

Pesguard FG161™, a mixture of d-tetramethrin and cyphenothrin (1:3 ratio), is extensively used to achieve rapid control of adult dengue vector, Aedes aegypti, during the disease outbreaks. Both d-tetramethrin and cyphenothrin are synthetic pyrethroids that are known to have adverse effects on non-mammalian organisms such as fish. The present study intended to use zebrafish embryo toxicity model to investigate the toxic effect of the above binary mixture on fish. Particularly, zebrafish embryo toxicity model provides an alternative to acute fish toxicity tests in terms of animal welfare perspective as the embryos are not considered live until 5 days after fertilization. The zebrafish embryos (2 hrs after fertilization) were exposed to a binary mixture of pyrethroids at different concentrations (d-tetramethrin: 0.01 – 1.20 μmolL-1 and cyphenothrin: 0.03 – 3.20 μmolL-1) for 24, 48, and 72 hrs at room temperature (26°C) according to the OECD guideline no. 236. Percentage mortality of embryos were calculated by observing the lethal endpoints and LC50 values were calculated for each time interval employing the probit analysis. This binary mixture was highly toxic to zebrafish embryos and was found to be concentration and time dependent. LC50 values at 24 hrs (d-tet: 0.58 μmolL-1, cyp: 1.74 μmolL-1) were significantly reduced in 48 hrs (d-tet: 0.11 μmolL-1, cyp: 0.33 μmolL-1) and 72 hrs (d-tet: 0.03 μmolL-1, cyp: 0.09 μmolL-1). Coagulation of embryos was the most common lethal effect observed and lack of somite formation and lack of heartbeat were also observed. The present study revealed that the binary mixture is highly toxic to zebrafish embryos even when based on nominal concentrations. Hence, extensive use of these pesticides could be detrimental to fish population and integrated vector control methods which involve the minimum use of insecticides are recommended. Further, this study highlights the applicability of zebrafish embryo toxicity model as an alternative method to investigate the toxicity of pyrethroids to fish

Nucleosome compaction facilitates HP1γ binding to methylated H3K9

The α, β and γ isoforms of mammalian heterochromatin protein 1 (HP1) selectively bind to methylated lysine 9 of histone H3 via their chromodomains. Although the phenotypes of HP1-knockout mice are distinct for each isoform, the molecular mechanisms underlying HP1 isoform-specific function remain elusive. In the present study, we found that in contrast to HP1α, HP1γ could not bind tri-methylated H3 lysine 9 in a reconstituted tetra-nucleosomes when the nucleosomes were in an uncompacted state. The hinge region connecting HP1's chromodomain and chromoshadow domain contributed to the distinct recognition of the nucleosomes by HP1α and HP1γ. HP1γ, but not HP1α, was strongly enhanced in selective binding to tri-methylated lysine 9 in histone H3 by the addition of Mg[2+] or linker histone H1, which are known to induce compaction of nucleosomes. We propose that this novel property of HP1γ recognition of lysine 9 in the histone H3 tail in different nucleosome structures plays a role in reading the histone code