Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines
Acharya Balkrishna,1,2 Sudeep Verma,1 Siva Kumar Solleti,1 Lakshmipathi Khandrika,1 Anurag Varshney1,2 1Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand 249 405, India; 2Department of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakh...
Guardado en:
Autores principales: | , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Dove Medical Press
2020
|
Materias: | |
Acceso en línea: | https://doaj.org/article/8dd5cc329f8a40a6a8657863e49bd77e |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:8dd5cc329f8a40a6a8657863e49bd77e |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:8dd5cc329f8a40a6a8657863e49bd77e2021-12-02T15:06:09ZCalcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines1178-7031https://doaj.org/article/8dd5cc329f8a40a6a8657863e49bd77e2020-12-01T00:00:00Zhttps://www.dovepress.com/calcio-herbal-medicine-divya-swasari-vati-ameliorates-sars-cov-2-spike-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Acharya Balkrishna,1,2 Sudeep Verma,1 Siva Kumar Solleti,1 Lakshmipathi Khandrika,1 Anurag Varshney1,2 1Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand 249 405, India; 2Department of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand 249 405, IndiaCorrespondence: Anurag Varshney Tel +91-1334-244107, Ext: 7458Email anurag@prft.co.inPurpose: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection has grown into a pandemic and without a specific cure, disease management is the need of the hour through symptomatic interventions. Studies with severe acute respiratory syndrome-coronavirus (SARS-CoV) have highlighted the role of herbal medicines either in combination with antiviral drugs or by themselves in curtailing the severity of infection and associated inflammation. Divya-Swasari-Vati is an Indian ayurvedic formulation used in the treatment of chronic cough and lung inflammation, which is one of the first symptoms of SARS-CoV-2 infections.Methods: In this study, we used a A549 cell xenotransplant in the swim bladder of zebrafish and modeled the SARS-CoV-2 infection by injecting the fish with a recombinant spike protein. The different groups were given normal feed or feed mixed with either dexamethasone (as the control drug) or Divya-Swasari-Vati. The changes in behavioral fever, infiltration of pro-inflammatory cells in the swim bladder, degeneration or presence of necrotic cells in the kidney, and gene expression of pro-inflammatory cytokines were studied to determine the rescue of the diseased phenotype.Results: Challenge with the spike protein caused changes in the swim bladder cytology with infiltrating pro-inflammatory cells, skin hemorrhage, and increase in behavioral fever. This was also accompanied by increased mortality of the disease control fish. Treatment with Divya-Swasari-Vati reversed most of the disease symptoms including damage to the kidney glomerulocytes, and complete reversal of behavioral fever. Dexamethasone, used as a comparator, was only able to partly rescue the behavioral fever phenotype. Divya-Swasari-Vati also suppressed the pro-inflammatory cytokines, IL-6 and TNF-α, levels in a dose-dependent manner, under in vivo and in vitro conditions.Conclusion: The study showed that the A549 xenotransplanted zebrafish injected with the recombinant spike protein of SARS-CoV-2 is an efficient model for the disease; and treatment with Divya-Swasari-Vati medicine rescued most of the inflammatory damage caused by the viral spike protein while increasing survival of the experimental fish.Keywords: zebrafish, A549 xenotransplant, SARS-CoV-2 infection model, herbal medicines, ayurveda, Divya-Swasari-Vati, behavioral fever, cytokine profileBalkrishna AVerma SSolleti SKKhandrika LVarshney ADove Medical Pressarticlezebrafisha549 xenotransplantsars-cov-2 infection modelherbal medicinesayurvedadivya-swasari-vatibehavioral fevercytokine profilePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 13, Pp 1219-1243 (2020) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
zebrafish a549 xenotransplant sars-cov-2 infection model herbal medicines ayurveda divya-swasari-vati behavioral fever cytokine profile Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
spellingShingle |
zebrafish a549 xenotransplant sars-cov-2 infection model herbal medicines ayurveda divya-swasari-vati behavioral fever cytokine profile Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Balkrishna A Verma S Solleti SK Khandrika L Varshney A Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines |
description |
Acharya Balkrishna,1,2 Sudeep Verma,1 Siva Kumar Solleti,1 Lakshmipathi Khandrika,1 Anurag Varshney1,2 1Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand 249 405, India; 2Department of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand 249 405, IndiaCorrespondence: Anurag Varshney Tel +91-1334-244107, Ext: 7458Email anurag@prft.co.inPurpose: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection has grown into a pandemic and without a specific cure, disease management is the need of the hour through symptomatic interventions. Studies with severe acute respiratory syndrome-coronavirus (SARS-CoV) have highlighted the role of herbal medicines either in combination with antiviral drugs or by themselves in curtailing the severity of infection and associated inflammation. Divya-Swasari-Vati is an Indian ayurvedic formulation used in the treatment of chronic cough and lung inflammation, which is one of the first symptoms of SARS-CoV-2 infections.Methods: In this study, we used a A549 cell xenotransplant in the swim bladder of zebrafish and modeled the SARS-CoV-2 infection by injecting the fish with a recombinant spike protein. The different groups were given normal feed or feed mixed with either dexamethasone (as the control drug) or Divya-Swasari-Vati. The changes in behavioral fever, infiltration of pro-inflammatory cells in the swim bladder, degeneration or presence of necrotic cells in the kidney, and gene expression of pro-inflammatory cytokines were studied to determine the rescue of the diseased phenotype.Results: Challenge with the spike protein caused changes in the swim bladder cytology with infiltrating pro-inflammatory cells, skin hemorrhage, and increase in behavioral fever. This was also accompanied by increased mortality of the disease control fish. Treatment with Divya-Swasari-Vati reversed most of the disease symptoms including damage to the kidney glomerulocytes, and complete reversal of behavioral fever. Dexamethasone, used as a comparator, was only able to partly rescue the behavioral fever phenotype. Divya-Swasari-Vati also suppressed the pro-inflammatory cytokines, IL-6 and TNF-α, levels in a dose-dependent manner, under in vivo and in vitro conditions.Conclusion: The study showed that the A549 xenotransplanted zebrafish injected with the recombinant spike protein of SARS-CoV-2 is an efficient model for the disease; and treatment with Divya-Swasari-Vati medicine rescued most of the inflammatory damage caused by the viral spike protein while increasing survival of the experimental fish.Keywords: zebrafish, A549 xenotransplant, SARS-CoV-2 infection model, herbal medicines, ayurveda, Divya-Swasari-Vati, behavioral fever, cytokine profile |
format |
article |
author |
Balkrishna A Verma S Solleti SK Khandrika L Varshney A |
author_facet |
Balkrishna A Verma S Solleti SK Khandrika L Varshney A |
author_sort |
Balkrishna A |
title |
Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines |
title_short |
Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines |
title_full |
Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines |
title_fullStr |
Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines |
title_full_unstemmed |
Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines |
title_sort |
calcio-herbal medicine divya-swasari-vati ameliorates sars-cov-2 spike protein-induced pathological features and inflammation in humanized zebrafish model by moderating il-6 and tnf-α cytokines |
publisher |
Dove Medical Press |
publishDate |
2020 |
url |
https://doaj.org/article/8dd5cc329f8a40a6a8657863e49bd77e |
work_keys_str_mv |
AT balkrishnaa calcioherbalmedicinedivyaswasarivatiamelioratessarscov2spikeproteininducedpathologicalfeaturesandinflammationinhumanizedzebrafishmodelbymoderatingil6andtnfalphacytokines AT vermas calcioherbalmedicinedivyaswasarivatiamelioratessarscov2spikeproteininducedpathologicalfeaturesandinflammationinhumanizedzebrafishmodelbymoderatingil6andtnfalphacytokines AT solletisk calcioherbalmedicinedivyaswasarivatiamelioratessarscov2spikeproteininducedpathologicalfeaturesandinflammationinhumanizedzebrafishmodelbymoderatingil6andtnfalphacytokines AT khandrikal calcioherbalmedicinedivyaswasarivatiamelioratessarscov2spikeproteininducedpathologicalfeaturesandinflammationinhumanizedzebrafishmodelbymoderatingil6andtnfalphacytokines AT varshneya calcioherbalmedicinedivyaswasarivatiamelioratessarscov2spikeproteininducedpathologicalfeaturesandinflammationinhumanizedzebrafishmodelbymoderatingil6andtnfalphacytokines |
_version_ |
1718388596046561280 |