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Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis

View ORCID ProfileZaigham Abbas Rizvi, Prabhakar Babele, Srikanth Sadhu, Upasna Madan, Manas Ranjan Tripathy, Sandeep Goswami, Shailendra Mani, Sachin Kumar, Amit Awasthi, Madhu Dikshit
doi: https://doi.org/10.1101/2022.05.16.492112
Zaigham Abbas Rizvi
1Immuno-biology Lab, Infection and Immunology centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
2Immunology-Core Lab, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
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  • ORCID record for Zaigham Abbas Rizvi
Prabhakar Babele
3Noncommunicable disease centre, Translational Health Science and Technology Institute (THSTI), NCR Biotech Science Cluster, 3rd Milestone, Faridabad - 121001, Haryana, India
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Srikanth Sadhu
1Immuno-biology Lab, Infection and Immunology centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
2Immunology-Core Lab, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
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Upasna Madan
1Immuno-biology Lab, Infection and Immunology centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
2Immunology-Core Lab, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
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Manas Ranjan Tripathy
1Immuno-biology Lab, Infection and Immunology centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
2Immunology-Core Lab, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
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Sandeep Goswami
1Immuno-biology Lab, Infection and Immunology centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
2Immunology-Core Lab, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
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Shailendra Mani
3Noncommunicable disease centre, Translational Health Science and Technology Institute (THSTI), NCR Biotech Science Cluster, 3rd Milestone, Faridabad - 121001, Haryana, India
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Sachin Kumar
4Pharmacology Division, CSIR-Central Drug Research Institute, Sitapur Rd, Sector 10, Jankipuram Extension, Lucknow, Uttar Pradesh 226031
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Amit Awasthi
1Immuno-biology Lab, Infection and Immunology centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
2Immunology-Core Lab, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India
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  • For correspondence: drmadhudikshit@gmail.com madhu.dikshit@cdri.res.in aawasthi@thsti.res.in
Madhu Dikshit
3Noncommunicable disease centre, Translational Health Science and Technology Institute (THSTI), NCR Biotech Science Cluster, 3rd Milestone, Faridabad - 121001, Haryana, India
4Pharmacology Division, CSIR-Central Drug Research Institute, Sitapur Rd, Sector 10, Jankipuram Extension, Lucknow, Uttar Pradesh 226031
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  • For correspondence: drmadhudikshit@gmail.com madhu.dikshit@cdri.res.in aawasthi@thsti.res.in
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Abstract

Severe coronavirus disease (COVID-19) is accompanied with acute respiratory distress syndrome & pulmonary pathology, and is presented mostly with inflammatory cytokine release, dysregulated immune response, skewed neutrophil/ lymphocyte ratio, and hypercoagulable state. Though vaccinations have proved effective in reducing the COVID-19 related mortality, the limitation of use of vaccine against immunocompromised, comorbidity, and emerging variants remains a concern. In the current study we investigate for the first-time the efficacy of Glycyrrhiza glabra (GG) extract, a potent immunomodulator, against SARS-CoV-2 infection in hamsters. Prophylactic treatment with GG showed protection against loss in body weight and 35-40% decrease in lung viral load along with reduced lung pathology in the hamster model. Remarkably, GG reduced the mRNA expression of pro-inflammatory cytokines and Plasminogen activator inhibito-1 (PAI-1). In-vitro, GG acted as potent immunomodulator by reducing Th2 and Th17 differentiation and IL-4 and IL-17A cytokine production. In addition, GG also showed robust potential to suppress ROS, mtROS and NETs generation in a concentration dependent manner in both human polymorphonuclear neutrophils (PMNs) and murine bone marrow derived neutrophils (BMDNs). Taken together, we provide evidence for the protective efficacy of GG against COVID-19 and its putative mechanistic insight, which might be developed as a future immunomodulatory approach against various pathologies with high cytokine production, aberrant neutrophil activation including coronavirus infection.

Competing Interest Statement

The authors have declared no competing interest.

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Posted May 17, 2022.
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Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis
Zaigham Abbas Rizvi, Prabhakar Babele, Srikanth Sadhu, Upasna Madan, Manas Ranjan Tripathy, Sandeep Goswami, Shailendra Mani, Sachin Kumar, Amit Awasthi, Madhu Dikshit
bioRxiv 2022.05.16.492112; doi: https://doi.org/10.1101/2022.05.16.492112
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Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis
Zaigham Abbas Rizvi, Prabhakar Babele, Srikanth Sadhu, Upasna Madan, Manas Ranjan Tripathy, Sandeep Goswami, Shailendra Mani, Sachin Kumar, Amit Awasthi, Madhu Dikshit
bioRxiv 2022.05.16.492112; doi: https://doi.org/10.1101/2022.05.16.492112

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