Assessment of aquo-ethanolic extract of Camellia sinensis against Carbapenem Resistant Escherichia coli: In Vivo Trials in a Murine Model

• Camellia sinensis (PTRC-31911-A) aquo-ethanolic (1:1) leaf extract was characterized using Liquid Chromatography Mass Spectrometry (LCMS) Analysis.
• LCMS analysis revealed the presence of polyphenols and flavonoids i.e., quercetin glycoside, epigallo-catechin gallate, gallo catechin, caffeine and gallic acid as the predominant phytoconstituents.
• Maximum reduction in microbial count (anti-CRE potential ∼ 90%) was observed at 5 mg/Kg bwt (oral) in both blood and urine samples.
• Physical, hematological, immunological and histopathological manifestations of CRE infected Sprague Dawley rats showed significant aberrations, which were restored in case of PTRC-31911-A treated rats (5 mg/Kg bwt; oral; +24 h).
• PTRC-31911-A exhibited no signs of any acute toxicity up to the maximum administered dose of 2000 mg/Kg bwt (oral).

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 = 126.83 g, ∼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 5 mg/Kg bwt; oral, + 24 h) 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.

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