Evaluation of the Role of Merromoside from Ipomoea aquatica Forsskal Hydroalcoholic Extract in the Downregulation of ROS Species in Overcoming MDR in Breast Cancer.

PURPOSE: The medicinal plant Ipomoea aquatica belonging to convulvulaceae family is an effective natural herb for treatment of various ailments and possesses effective anticancer activity. The aim of the work is to characterize a secondary metabolite merromoside (a resin glycoside) for anti-breast cancer activity through down regulation of ROS species. METHODS: The Extract of the whole plant has been prepared by maceration method using 50%v/v ethanol in distilled water to get a hydroalcoholic extract. The phytochemical evaluation reveals that the active secondary metabolite was isolated by using column chromatographic technique. The isolated compound was evaluated for its anticancer properties through invitro method such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on Michigan Cancer Foundation-7 Cell lines. The purity and structural characterization were done by high-performance thin layer chromatography, Fourier Transform Infrared Spectroscopy, Proton and13C Nuclear Magnetic Resonance spectroscopy and Liquid Chromatography-Mass Spectrometry. RESULTS: The isolated compound (W04) from the derived extract showed Rf value of 0.79 that showed IC50 of 182.8µg/ml. The chemical structure of W04 has been confirmed as [4,5-dihydroxy-6-[5-hydroxy-2-methyl-4-(2-methylpropanoyloxy)-6-[(24,25,26-trihydroxy-5,23-dimethyl-9-oxo-19-pentyl-2,4,8,20,22-pentaoxatricyclo[19.2.2.13,7]hexacosan-6-yl)oxy]oxan-3-yl]oxy-2-methyloxan-3-yl] 2-methyl propanoate with the molecular weight of 979.15268. The isolated compound merromoside from hydroalcoholic extract of Ipomoea aquatica has been evaluated for anti-breast cancer properties. The down regulation of ROS species will prevent reverse signalling and angiogenesis. This indicates that merromoside will overcome MDR in breast cancer especially DOX-resistant.

Clinical outcomes in individuals hospitalized with SARS-CoV-2 Delta variant (B.1.617.2) who had been vaccinated with Covishield (ChAdOx1) and Covaxin (BBV-152).

Background: Covishield (ChAdOx) and Covaxin (BBV-152) are the mainstream vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) used in India and a few other countries. Objective: To assess the clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) who had been vaccinated with either Covishield or Covaxin. Methods: This prospective, single-centre, observational cohort study of 1160 patients hospitalized with COVID-19 was conducted between April and June 2021. Severity of disease at admission and during hospitalization, requirement for intensive care unit (ICU) admission and ventilatory support, inflammatory markers (C-reactive protein, ferritin, lactate dehydrogenase, D-dimer), neutralizing antibody levels and mortality were assessed in vaccinated and unvaccinated patients. Results: More than 90% of patients in this study harboured the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Severity of disease at admission and during hospitalization (3.44% vs 7.51%; P=0.0032) and requirement for ICU admission and ventilatory support (2.83% vs 5.86%; P=0.0154) were significantly lower in vaccinated patients compared with unvaccinated patients. Vaccinated patients also had significantly (P<0.0001) higher antibody levels and lower inflammatory marker levels compared with unvaccinated patients. A subset of vaccinated, deceased patients mounted minimal antibody response ['non-responders': 4.53 (standard deviation 1.40) AU/mL]. Conclusion: These results demonstrate the effectiveness of Covishield and Covaxin against severe disease in patients hospitalized with COVID-19 with breakthrough infections caused by the Delta variant. Strategies targeting non-responders are desirable to minimize morbidity and mortality.

Rapid and ultra-rapid metabolizers with CYP2C19*17 polymorphism do not respond to standard therapy with proton pump inhibitors.

INTRODUCTION AND OBJECTIVE: Polymorphisms in genes encoding drug metabolizing enzymes may lead to varied enzyme activity and inter-individual variability in drug efficacy and/or toxicity. Since CYP2C19 and CYP3A4 genes code for enzymes involved in metabolizing wide variety of drugs including proton pump inhibitors, we sought to identify polymorphisms in these genes in order to study their impact on drug metabolism in subjects. METHODS: DNA was isolated from healthy individuals including tribals and genotyped for 11 single nucleotide polymorphisms in CYP2C19 and 6 polymorphisms in CYP3A4. Individuals were categorized into different phenotypes based on their drug metabolizing genotype. Volunteers from each group were administered proton pump inhibitors (Esomeprazole, Pantoprazole; 40 mg/day) for 5 days followed by pharmacokinetic studies and measurement of intra-gastric pH. RESULTS: Of the 17 polymorphisms studied, only CYP2C19*2,*3,*17 and CYP3A4*1B polymorphisms were observed. In comparison to urban individuals, a significantly (p = 0.0003) higher number of poor metabolizers were noted in the tribal individuals. Pantoprazole was found to be most effective in poor metabolizers in terms of area under the curve and Tmax. No significant difference was observed in the intra-gastric pH at baseline and day 6 in rapid and ultra-rapid metabolizers. CONCLUSION: Our study has demonstrated that 19.7% of our subjects are carriers of the CYP2C19*17 allele who did not respond to the standard dose of proton pump inhibitors. Genetic screening to identify subjects with variant alleles would thus be useful for personalization of therapy with proton pump inhibitors.