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Open AccessArticle

Validation of a Novel Zebrafish Model of Dengue Virus (DENV-3) Pathology Using the Pentaherbal Medicine Denguenil Vati

1
Drug Discovery and Development Division, Patanjali Research Institute, NH-58, Haridwar 249 405, Uttarakhand, India
2
Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Roorkee-Haridwar Road, Haridwar 249 405, Uttarakhand, India
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(7), 971; https://doi.org/10.3390/biom10070971
Received: 18 May 2020 / Revised: 19 June 2020 / Accepted: 22 June 2020 / Published: 28 June 2020
(This article belongs to the Special Issue Zebrafish: A Model for the Study of Human Diseases)
Dengue is a devastating viral fever of humans, caused by dengue virus. Using a novel zebrafish model of dengue pathology, we validated the potential anti-dengue therapeutic properties of pentaherbal medicine, Denguenil Vati. At two different time points (at 7 and 14 days post infection with dengue virus), we tested three translational doses (5.8 μg/kg, 28 μg/kg, and 140 μg/kg). Dose- and time-dependent inhibition of the viral copy numbers was identified upon Denguenil Vati treatment. Hepatocyte necrosis, liver inflammation, and red blood cell (RBC) infiltration into the liver were significantly inhibited upon Denguenil treatment. Treatment with Denguenil Vati significantly recovered the virus-induced decreases in total platelet numbers and total RBC count, and concomitantly increasing hematocrit percentage, in a dose- and time-dependent manner. Conversely, virus-induced white blood cell (WBC) counts were significantly normalized. Virus-induced hemorrhage was completely abrogated by Denguenil after 14 days, at all the doses tested. Gene expression analysis identified a significant decrease in disease-induced endothelial apoptotic marker Angiopoetin2 (Ang-2) and pro-inflammatory chemokine marker CCL3 upon Denguenil treatment. Presence of gallic acid, ellagic acid, palmetin, and berberine molecules in the Denguenil formulation was detected by HPLC. Taken together, our results exhibit the potential therapeutic properties of Denguenil Vati in ameliorating pathological features of dengue.
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Keywords: dengue virus; DENV; zebrafish model; gene expression; Denguenil Vati dengue virus; DENV; zebrafish model; gene expression; Denguenil Vati
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Balkrishna, A.; Solleti, S.K.; Verma, S.; Varshney, A. Validation of a Novel Zebrafish Model of Dengue Virus (DENV-3) Pathology Using the Pentaherbal Medicine Denguenil Vati. Biomolecules 2020, 10, 971.

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