Validation of a Novel Zebrafish Model of Dengue Virus (DENV-3) Pathology Using the Pentaherbal Medicine Denguenil Vati
Authors: Sudeep Verma
Acharya Balkrishna
Anurag Varshney
Siva Kumar Solleti
Journal: Biomolecules (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: DENV; Denguenil Vati; dengue virus; gene expression; zebrafish model.
Affiliations: Drug Discovery and Development Division, Patanjali Research Institute, NH-58, Haridwar 249 405, Uttarakhand, India., Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Roorkee-Haridwar Road, Haridwar 249 405, Uttarakhand, India.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Unfortunately the authors did not make clear if the singing depicted in the accompanying video was a required element in the treatment with this Indian traditional pentaherbal formulation, or merely provided as entertainment for the u201creviewers.u201d *** ![file] , 
 The product pictured and the research university appear to be connected with the Divya Yog Mandir Trust. This paper may in fact be an advertisement for this product, although the authors claim no conflicts of interest. Could the authors explain the relationships here? https: www.patanjaliayurved.net about *** ![file] *** ![file] , 
 Perhaps the first author can explain how this Tweet can be reconciled with the conflict of interest statement in this u201cresearch paper.u201d https: twitter.com ach_balkrishna status 1185913916326440960?s=21 , 
  *Zebrafish were anesthetized by placing them in ice water (18 u25e6C).* 18 degrees Celcius does not seem to be that cold. Are the authors sure the zebrafish were adequately anesthetized? ![file] , 
 Virologists have always thought that only humans and some monkey species (and a mosquito species) could host the dengue virus, but now we know that fish are vulnerable as well. [ Several studies, reviewed by Simmons et al. [9] in 1931, showed that a broad range of animals, namely chickens, pigeons, other fowl, goats, dogs, pigs, lizards, guinea pigs, rabbits, rats, mice and hamsters show no signs of dengue disease, even after inoculation of high virus doses, by different routes. ] ,