title: Assessment of aquo-ethanolic extract of Camellia sinensis against Carbapenem Resistant Escherichia coli: In Vivo Trials in a Murine Model.
abstract: The prevalence of Carbapenem Resistant Escherichia coli (CRE) has increased considerably during the last decade, which can be ascribed to relative scarcity of effective non toxic antimicrobial agents. The present study was conducted to evaluate the antimicrobial activity of aquo-ethanolic (1:1) extract of leaves of Camellia sinensis (PTRC-31911-A) against Carbapenem Resistant Escherichia coli at preclinical level using peritonitis infection model in Sprague Dawley rats. Efficacy analysis of PTRC-31911-A involved enumeration of CRE colonies in blood and urine samples of test animals for a period of 5 days from infection. A reduction in microbial count of biological fluids was considered as the primary endpoint of the selected murine model. Physical, biochemical, hematological and histological indices of toxicity were employed as secondary relative indicators of the induced disease. Physical manifestations of infected rats included significantly high body temperature (TempInfected=103.18°F, ∼5% increase) and noteworthy reduction in weight (WeightInfected=126.83g, ∼15% decrease) as compared to control. Significant (P<0.05) increase in total white blood cells, eosinophil and monocyte counts as well as a significant decrease (P<0.05) in erythrocytes count, hematocrit volume, red blood cell distribution width and hemoglobin concentration were observed in the infected group as compared to the control group. Furthermore, noteworthy increase in liver and kidney function test parameters were observed in case of infected groups. All the hematological and biochemical parameters were found to be within optimum range in case of treatment group, indicating restoration of homeostasis. Histopathological studies also presented symptoms of hemorrhage and glomerular damage with structural distortion in glomerular capillary loops of infected groups, which were later recovered in treated groups, indicating the nephro-protective potential of PTRC-31911-A. The study clearly points out that Camellia sinensis extract (PTRC-31911-A; single dose of 5mg/Kg bwt; oral,+24h) is highly effective against Carbapenem Resistant Escherichia coli owing mainly to the presence of flavonoids and polyphenolic compounds, identified by LCMS. Ongoing studies are expected to further unravel the mechanism of action and bioactivity determinants of this broad spectrum plant extract.
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Thakur
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India. Electronic address: ptrcmanuscripts@gmail.com.
authors.forename: Raman
authors.initials: R
authors.lastname: Chawla
authors.affiliation: Department of Biotechnology, Jamia Hamdard, Delhi, India.
authors.forename: Alka
authors.initials: A
authors.lastname: Narula
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Goel
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India; Directorate General-Life Sciences, Defence Research and Development Organisation, DRDO Bhawan, Delhi, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Arora
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000818:Animals; D028241:Camellia sinensis / Q000737:chemistry*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use*; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects*; D000431:Ethanol; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D020714:Maximum Tolerated Dose; D051379:Mice; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D014867:Water
chemical_list: D015780:Carbapenems; D010936:Plant Extracts; D014867:Water; D000431:Ethanol
keywords: Antimicrobial Resistance; Camellia sinensis; Carbapenem Resistant Escherichia coli; Metallo-Beta-Lactamase; in vivo; therapeutic efficacy