Poloxamer 188 – quercetin formulations amplify in vitro ganciclovir antiviral activity against cytomegalovirus

Kjar, Andrew; Wadsworth, Ian D.; Vargis, Elizabeth; Britt, David W.

doi:10.1016/j.antiviral.2022.105362

Cited by 5 publications

(16 citation statements)

References 44 publications

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“…According to some researchers, it can enhance the antiviral activity of cells after being specially prepared. [41] Mechanism studies showed that quercetin was selected as an inhibitor against SARS-CoV-2 which was mediated by blocking the 3a channel, inhibiting protein kinase B and phosphorylating protein kinase. [42,43] Other studies showed that the compound also has the function of regulating immune responses by reducing pro-inflammatory cytokines and enhancing anti-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and bioinformatics to identify molecular mechanisms and therapeutic targets of Ruyi Jinhuang Powder in the treatment of monkeypox

Zhang

et al. 2023

Medicine

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Monkeypox outbreaks across the globe has aroused widespread concern. Ruyi Jinhuang Powder (RJP), a common formula in Chinese medicine, is used to treat pox-like illnesses. This study aimed to identify the molecular mechanisms and therapeutic targets of RJP for the treatment of monkeypox using network pharmacology and bioinformatics techniques. The bioactive substances and potential targets of each component of RJP were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The differentially expressed genes (DEGs) of the monkeypox virus (MPXV) were identified from the GSE24125 by GEO2R. Key signaling pathways, bioactive components, and potential targets were obtained by bioinformatics analysis, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), disease ontology (DO), and protein-protein interactions (PPI) analyses. Finally, molecular docking was used to predict the interaction between active compounds and core targets. A total of 158 active ingredients and 17 drug-disease-shared targets of RJP were screened. Bioinformatics indicated that wogonin and quercetin might be potential drug candidates. Potential therapeutic targets were identified. Immune-related mechanisms that exerted antiviral effects included signaling pathways like TNF, age-rage, and c-type lectin receptor pathways. Our results illustrated the good therapeutic effect of RJP on monkeypox in terms of biological activity, potential targets, and molecular mechanism. This also offered a promising strategy to reveal the scientific basis and therapeutic mechanism of herbal formulas used to treat the disease.

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Section: Discussionmentioning

confidence: 99%

Network pharmacology and bioinformatics to identify molecular mechanisms and therapeutic targets of Ruyi Jinhuang Powder in the treatment of monkeypox

Zhang

et al. 2023

Medicine

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“…Using MitoView™ 405 dye, our group has previously demonstrated mitochondrial localization of these two excipients as well as additive and synergistic antiviral activity with GCV in a CMV-infected 3T3 fibroblast cell culture. 11 Our group has also previously demonstrated amelioration of CMV-induced sensorineural hearing loss in mice using GCV as well as antioxidants. 12,13 The purpose of this study was to investigate the effects of combination therapy between quercetin, P188, and GCV in an established in vivo murine model.…”

Section: Introductionmentioning

confidence: 91%

“…Quercetin was solubilized in saline using poloxamer 188 (QP188) and blank solutions of P188 were prepared using the thin-film hydration method as previously described (Kolliphor ® P188 BIO). 11 Ganciclovir (GCV, Sigma-Aldrich, Inc., St. Louis, MO) was dissolved into solution using sterile normal saline. GCV and QP188 formulations were mixed into a single solution for combination therapy (GCV+QP188).…”

Section: Gcv Qp188 and P188 Formulationsmentioning

confidence: 99%

“…Murine stria vascularis (SV) endothelial cell cultures were supplied by Dr. Xiaorui Shi (Portland, OR, USA) and prepared as previously described by Neng et al 16 These cells were infected with mCMV-GFP as previously described. 11 Briefly, SV cells were seeded onto a VWR ® Standard plasma-treated polystyrene 96-well plate and allowed to adhere for 4 h at 37 C, 5% CO 2 . One hundred microliter of warm viral inoculum media was added to the wells with an inoculation density of 3 Â 10 3 pfu/well and a multiplicity of infection (MOI) of 0.3.…”

Section: Cell Culture and Viral Infectionmentioning

confidence: 99%

“…19 Fluorescent Labeling of P188 and Imaging P188 was fluorescently tagged using 5-(and 6-) carboxy-2 0 7 0dichlorofluorescein (44 μmol) as previously described (F-P188). 11 Stria vascularis endothelial cells were stained with either F-P188 or F-QP188 for 4 h in a six-well glass-bottom plate (In Vitro Scientific). Cells were then counterstained with NucBlue nuclear stain (Thermo Fisher) for 15 min.…”

Section: Antiviral Gfp Assay (Ec 50 and Fic)mentioning

confidence: 99%

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Can Ganciclovir and Quercetin‐P188 Ameliorate Cytomegalovirus Induced Hearing Loss?

Suarez,

Kjar,

Scott

et al. 2023

The Laryngoscope

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ObjectiveDetermine whether combination therapy with ganciclovir (GCV) and a Quercetin‐P188 solution improves hearing outcomes in a murine cytomegalovirus (CMV) model.MethodsBALB/c mice were infected with murine CMV on postnatal day 3 (p3). Quercetin was solubilized in saline using P188 (QP188). Treatment groups received either GCV, QP188, GCV and QP188, or P188 delivery vehicle BID at 12‐hour intervals via intraperitoneal injection. All treatment groups were treated for 14 days starting at p3. Uninfected controls were treated with the combined regimen, saline or P188 delivery vehicle. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Temporal bones from separate CMV‐infected groups were harvested at p10, and viral load was determined by quantitative polymerase chain reaction.ResultsCMV‐infected mice receiving combination therapy GCV+QP188 demonstrated statistically significant lower ABR (p < 0.001) and DPOAE thresholds (p < 0.001) compared with mice treated with GCV monotherapy, QP188 monotherapy, and P188 delivery vehicle at 4, 6, and 8 weeks of age. GCV+QP188 combination therapy, GCV monotherapy, and QP188 monotherapy resulted in a nonsignificant reduction in mean viral titers compared to P188 monotherapy (p = 0.08).ConclusionCombining GCV with the excipients quercetin and P188 effectively ameliorated CMV‐induced sensorineural hearing loss in a murine model. This result may be partially explained by a reduction in viral titers in mouse temporal bones that correlate with in vitro studies demonstrating additive antiviral effect in cell culture.Level of EvidenceNA Laryngoscope, 2023

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Nano-emulsomes for back of the eye delivery of Ganciclovir: formulation optimization, characterization & in vitro/in vivo evaluation

Kapadia

Jain

Patel

et al. 2023

Pharmaceutical Development and Technology

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Poloxamer 188 – quercetin formulations amplify in vitro ganciclovir antiviral activity against cytomegalovirus

Cited by 5 publications

References 44 publications

Network pharmacology and bioinformatics to identify molecular mechanisms and therapeutic targets of Ruyi Jinhuang Powder in the treatment of monkeypox

Network pharmacology and bioinformatics to identify molecular mechanisms and therapeutic targets of Ruyi Jinhuang Powder in the treatment of monkeypox

Can Ganciclovir and Quercetin‐P188 Ameliorate Cytomegalovirus Induced Hearing Loss?

Nano-emulsomes for back of the eye delivery of Ganciclovir: formulation optimization, characterization & in vitro/in vivo evaluation

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