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

Balkrishna, Acharya; Solleti, Siva Kumar; Verma, Sudeep; Varshney, Anurag

doi:10.3390/biom10070971

Cited by 12 publications

(8 citation statements)

References 76 publications

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“…Clinically, C. papaya extracts have been shown to elevate the platelet count of Dengue patients [ 28 , 29 ]. DNV also induced similar effects in restoration of reduced platelet counts, in an animal model of Dengue virus infection [ 7 ]. C. papaya is a rich source of bioactive molecule rutin [ 30 ], Vitamins A, C and E [ 31 ] which helps the body to gain nourishment, boost immunity and lead to fast recovery [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

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Identification, Validation and Standardization of Bioactive Molecules Using UPLC/MS-QToF, UHPLC and HPTLC in Divya-Denguenil-Vati: A Penta-Herbal Formulation for Dengue Fever

et al. 2022

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For the last fifty years, Dengue has been one of the most common mosquito-borne arboviral infections which has spread over the tropical and subtropical world. Divya-Denguenil-Vati (DNV) has been formulated by blending five specific herbs for effective resolution of Dengue fever. In the present study, we aimed to identify, develop, validate, and standardize methods for Divya-Denguenil-Vati (DNV), on UHPLC and HPTLC analytical platforms, with rapid, sensitive, accurate and rugged attributes. At first, 97 phyto-constituents were identified by UPLC/MS-QToF in Divya-Denguenil-Vati. UHPLC method was then developed and validated for simultaneous determination of gallic acid, 5-HMF, protocatechuic acid, magnoflorine, methyl gallate, berberine, rutin, ellagic acid, β-ecdysone and rosmarinic acid in DNV. Four selected markers, gallic acid, rosmarinic acid, magnoflorine and rutin were further developed and validated on HPTLC. Analytical processes were validated as per ICH Q2 (R1) guidelines; and were found linear (r 2 > 0.99), sensitive, precise (%RSD < 5%), and accurate, as indicated by high recovery values (88-105%). The limit of detection and quantification were also established for these phytometabolites, with their respective RSDs within 5% limits. Finally, these validated methods were employed to test twenty six different commercial batches of DNV. The quality, reproducibility and consistency of DNV have been well established using these developed and reliable analytical tools. These analytical strategies successfully set a path forward for robust quality evaluation and standardization of Divya-Denguenil-Vati, and other related herbal formulations.

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Section: Discussionmentioning

confidence: 99%

“…These herbs have been described for their efficient therapeutic uses in the ancient medicinal texts. One of our previous studies has validated and established anti-dengue properties of poly-herbal medicine, Divya-Denguenil-Vati in the zebrafish model of disease [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Identification, Validation and Standardization of Bioactive Molecules Using UPLC/MS-QToF, UHPLC and HPTLC in Divya-Denguenil-Vati: A Penta-Herbal Formulation for Dengue Fever

et al. 2022

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“…Similarly, human prescribed dose of dexamethasone (DEX) is 6 mg/day (100 µg/kg) that was translated to 0.08 µg/kg for zebrafish. 13 After acclimatizing zebrafish in standard laboratory conditions for seven days, they were divided into six groups (Groups I–VI) of 24 fish each. At day 0, Group I and Group II were fed with the normal fish feed whereas Group III was fed with feed comprising of DEX at a dosage of 0.08 µg/kg.…”

Section: Methodsmentioning

confidence: 99%

Divya-Herbal-Peya Decoction Harmonizes the Inflammatory Response in Lipopolysaccharide-Induced Zebrafish Model

Balkrishna¹,

Lochab²,

Joshi³

et al. 2021

JEP

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Background: Divya-Herbal-Peya (DHP) is a plant-based decoction containing fourteen herbs in precise quantities; usually prescribed by the practitioners in Ayurveda to alleviate stress and minimize the exasperating symptoms of recurring infections. Our study aims to provide an experimental validation to the immunomodulatory properties of DHP. Methods: Physico-chemical analysis of DHP was performed to evaluate the presence of secondary metabolites. The phytochemicals were then identified and quantitated through HPTLC, UHPLC, and GC-MS techniques. To address the scientific rationale behind DHP, lipopolysaccharide (LPS) was intraperitoneally injected in adult zebrafish to develop inflammatory response. Following LPS-induction, abnormality in locomotory behaviour was determined by evaluating the relative swim velocity and the rate of turning in experimental zebrafish. Pathophysiological effects were determined through opercular frequency, behavioural fever, and caudal fin damage. LPS-mediated inflammation was measured of pro-inflammatory cytokines, TNFα, IL-6, and IL-1β expression in the serum of study animals, by RT-PCR. Results: Our study phytochemically characterized and ascertained the presence of glycyrrhizin, rosmarinic acid, gingerol, cinnamic acid, protocatechuic acid, gallic acid, ellagic acid, piperine and cinnamaldehyde in DHP decoction. LPS induced aberrant locomotory patterns, behavioural fever and caudal fin damage in zebrafish. A significant increase in gene expression levels of pro-inflammatory cytokines, TNFα, IL-6, and IL-1β was also determined. However, these locomotory deviations and behavioural fever were negligible in zebrafish groups preadministered either with DHP in a dose dependent manner or dexamethasone (DEX). The altered opercular rate, caudal fin damage and elevated transcription levels of pro-inflammatory genes upon LPS-induction were averted in groups pre-treated with DHP and DEX. Conclusion: DHP prophylactically prevented the LPS-induced abnormal behaviour and inflammation-related pathophysiology in zebrafish. Immunomodulatory properties of DHP may not have therapeutic intervention, but do confer nutraceutical health benefits against mild infections.

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“…Dengue virus (DENV) is a single-stranded, positive-sense, mosquito-borne Flavivirus that can induce a broad range of manifestations in infected humans, from asymptomatic to severe flu-like. Recently, Balkrishna et al (192) described an adult zebrafish model for Dengue virus serotype 3 (DENV-3) infection. The authors collected serum containing DENV-3 from human subjects and then performed intramuscular injections of serum into adult zebrafish that served as carriers to propagate the virus.…”

Section: Dengue Virusmentioning

confidence: 99%

“…After 14 days, serum from infected zebrafish was harvested, diluted, and injected intramuscularly into secondary adult zebrafish, which served as the study subjects. Using a qPCR-based approach to measure DENV-3specific transcripts, Balkrishna et al (192) observed a viral load that was sustained through 15 days post-injection. Histological analysis of the liver indicated necrosis, increased numbers of inflammatory cells, and increased presence of erythrocytes.…”

Section: Dengue Virusmentioning

confidence: 99%

Modeling Virus-Induced Inflammation in Zebrafish: A Balance Between Infection Control and Excessive Inflammation

et al. 2021

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The inflammatory response to viral infection in humans is a dynamic process with complex cell interactions that are governed by the immune system and influenced by both host and viral factors. Due to this complexity, the relative contributions of the virus and host factors are best studied in vivo using animal models. In this review, we describe how the zebrafish (Danio rerio) has been used as a powerful model to study host-virus interactions and inflammation by combining robust forward and reverse genetic tools with in vivo imaging of transparent embryos and larvae. The innate immune system has an essential role in the initial inflammatory response to viral infection. Focused studies of the innate immune response to viral infection are possible using the zebrafish model as there is a 4-6 week timeframe during development where they have a functional innate immune system dominated by neutrophils and macrophages. During this timeframe, zebrafish lack a functional adaptive immune system, so it is possible to study the innate immune response in isolation. Sequencing of the zebrafish genome has revealed significant genetic conservation with the human genome, and multiple studies have revealed both functional conservation of genes, including those critical to host cell infection and host cell inflammatory response. In addition to studying several fish viruses, zebrafish infection models have been developed for several human viruses, including influenza A, noroviruses, chikungunya, Zika, dengue, herpes simplex virus type 1, Sindbis, and hepatitis C virus. The development of these diverse viral infection models, coupled with the inherent strengths of the zebrafish model, particularly as it relates to our understanding of macrophage and neutrophil biology, offers opportunities for far more intensive studies aimed at understanding conserved host responses to viral infection. In this context, we review aspects relating to the evolution of innate immunity, including the evolution of viral pattern recognition receptors, interferons and interferon receptors, and non-coding RNAs.

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

Cited by 12 publications

References 76 publications

Identification, Validation and Standardization of Bioactive Molecules Using UPLC/MS-QToF, UHPLC and HPTLC in Divya-Denguenil-Vati: A Penta-Herbal Formulation for Dengue Fever

Identification, Validation and Standardization of Bioactive Molecules Using UPLC/MS-QToF, UHPLC and HPTLC in Divya-Denguenil-Vati: A Penta-Herbal Formulation for Dengue Fever

Divya-Herbal-Peya Decoction Harmonizes the Inflammatory Response in Lipopolysaccharide-Induced Zebrafish Model

Modeling Virus-Induced Inflammation in Zebrafish: A Balance Between Infection Control and Excessive Inflammation

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