Chemical Characterization of Different Extracts from Artemisia annua and Their Antioxidant,Enzyme Inhibitory and Anti-Inflammatory Properties

Artemisia annua L. (Asteraceae Family) is an important plant in Asia that has been used for treating different diseases, including fever due to malaria, wounds, tubercolisis, scabues, pain, convulsions, diabetes, and inflammation. In this study we aimed to evaluate the effects of different polarity extracts (hexane, dichloromethane, ethyl acetate, ethanol, ethanol/water (70 %) and water) from A. annua against the burden of inflammation and oxidative stress occurring in colon tissue exposed to LPS. In parallel, chemical composition, antiradical, and enzyme inhibition effects against α-amylase, α-glucosidase, tyrosinase, and cholinesterases were evaluated. The water extract contained the highest content of the total phenolic with 34.59 mg gallic acid equivalent (GAE)/g extract, while the hexane had the highest content of the total flavonoid (20.06 mg rutin equivalent (RE)/g extract). In antioxidant assays, the polar extracts (ethanol, ethanol/water and water) exhibited stronger radical scavenging and reducing power abilities when compared to non-polar extracts. The hexane extract showed the best AChE, tyrosinase and glucosidase inhibitory effects. All extracts revealed effective anti-inflammatory agents, as demonstrated by the blunting effects on COX-2 and TNFα gene expression. These effects seemed to be not related to the only phenolic content. However, it is worthy of interest to highlight how the higher potency against LPS-induced gene expression was shown by the water extract ; thus suggesting a potential phytotherapy application in the management of clinical symptoms related to inflammatory colon diseases, although future in vivo studies are needed to confirm such in vitro and ex vivo observations.     

Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant

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Risk Factors for Acquired Rifamycin and Isoniazid Resistance: A Systematic Review and Meta-Analysis

BackgroundStudies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies.MethodsCase-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I² statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies.ResultsMeta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I² 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I² 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5^th to 95^th percentile 0.07 to 3.2%).ConclusionBaseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR. The multifactorial aetiology of ADR in a programmatic setting should be further evaluated via appropriately designed studies.     

Homology modeling of human histone deacetylase 10 and design of potential selective inhibitors

Abstract

Histone deacetylases (HDACs) are implicated in the pathology of various cancers, and their pharmacological blockade has proven to be promising in reversing the malignant phenotypes. However, lack of crystal structures of some of the human HDAC isoforms (e.g., HDAC10) hinders the design of the isoform-selective inhibitor. Here, the recently solved X-ray crystal structure of Danio rerio (zebrafish) HDAC10 (Protein Data Bank (PDB) ID; 5TD7, released on 24 May 2017) was retrieved from the PDB and used as a template structure to model the three-dimensional structure of human HDAC10. The overall quality of the best model (M0017) was assessed by computing its z-score—a measure of the deviation of the total energy of the structure with respect to an energy distribution derived from random conformations and by docking of known HDAC10 inhibitors to its catalytic cavity. Furthermore, to identify potential HDAC10-selective inhibitor ligand-based virtual screening was carried out against the ZINC database. The free modeled structure of HDAC10 and its complexes with quisinostat and the highest-ranked compound ZINC19749069 were submitted to molecular dynamics simulation. The comparative analysis of root-mean-squared deviation, root-mean-squared fluctuation, radius of gyration (Rg), and potential energy of these systems showed that HDAC10-ZINC19749069 complex remained the most stable over time. Thus, M0017 could be potentially used for structure-based inhibitor against HDAC10, and ZINC19749069 may provide a scaffold for further optimization.

Communicated by Ramaswamy H. Sarma