Polyphenols Can Inhibit Furin In Vitro As A Result of the Reactivity of their Auto-oxidation Products to Proteins

Zhu, J.; Ven, W.J.M. Van de; Verbiest, T.; Koeckelberghs, Guy; Chen, C.; Cui, Yan-Ping; Vermorken, A.J.M.

doi:10.2174/092986713805076702

Cited by 13 publications

(17 citation statements)

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“…Moreover, our study suggests that RWPs may be both antioxidant and prooxidant because we observed an increase of ROS production when RPWs were added during H 2 O 2 oxidative stress. It is well known [ 43 ] that polyphenols extract could autoxidize and produce more hydrogen peroxide. In our study, we have demonstrated in this condition that RWPs have no impact on SOD or CAT protein expression but other protective mechanisms could be activated like the stimulation of CAT and SOD activity or a direct action glutathione or thioredoxin.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress Type Influences the Properties of Antioxidants Containing Polyphenols in RINm5F Beta Cells

Auberval

Dal

Bietiger

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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The in vitro methods currently used to screen bioactive compounds focus on the use of a single model of oxidative stress. However, this simplistic view may lead to conflicting results. The aim of this study was to evaluate the antioxidant properties of two natural extracts (a mix of red wine polyphenols (RWPs) and epigallocatechin gallate (EGCG)) with three models of oxidative stress induced with hydrogen peroxide (H2O2), a mixture of hypoxanthine and xanthine oxidase (HX/XO), or streptozotocin (STZ) in RINm5F beta cells. We employed multiple approaches to validate their potential as therapeutic treatment options, including cell viability, reactive oxygen species production, and antioxidant enzymes expression. All three oxidative stresses induced a decrease in cell viability and an increase in apoptosis, whereas the level of ROS production was variable depending on the type of stress. The highest level of ROS was found for the HX/XO-induced stress, an increase that was reflected by higher expression antioxidant enzymes. Further, both antioxidant compounds presented beneficial effects during oxidative stress, but EGCG appeared to be a more efficient antioxidant. These data indicate that the efficiency of natural antioxidants is dependent on both the nature of the compound and the type of oxidative stress generated.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress Type Influences the Properties of Antioxidants Containing Polyphenols in RINm5F Beta Cells

Auberval

Dal

Bietiger

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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“…EGCG, the main polyphenol of green tea, showed some bene cial effects on cognition in a phase II clinical trial with DS individuals (76). Interestingly, EGCG perfectly ts in the FURIN pocket and is therefore predicted to be a FURIN inhibitor (77)(78)(79). Concordantly, lipophilic EGCG derivatives showed antioxidant and antiviral properties (80).…”

Section: Antiviral Properties Of Egcgmentioning

confidence: 94%

Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19

Toma

Dierssen

2020

Preprint

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Background: SARS-CoV-2 has spread uncontrollably worldwide while we still ignore how particularly vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also suffer from multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes.Methods: In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we retrieved the genes belonging to the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We therefore analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) creating a DS-SARS-CoV-2 network.Results: We detected COVID-19 protective and risk factors that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome.Conclusion: Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells, even though the anti-viral interferon I signaling is upregulated in DS and this might increase the initial anti-viral response. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.

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“…Moreover, plant extracts may contain compound classes that are obstructive for certain assay types and might lead to false positive or false negative results. Particularly common highly apolar compounds, such as fatty acids (Balunas et al, 2006), common polar compounds, such as polyphenols and flavonoids (Zhu et al, 1997(Zhu et al, , 2013Zou et al, 2002), as well as chlorophyll (Henrich et al, 2006) might be especially problematic since they can interfere with a range of different assays. Much effort is necessary to remove such constituents from samples prior to testing (Cardellina et al, 1993;Collins et al, 1998;Picker et al, 2014) or to modify the assay system in order to avoid their detection (Sasiela et al, 2008).…”

Section: Challenges Contributing To the Decline Of Plant-derived Natumentioning

confidence: 99%

Discovery and resupply of pharmacologically active plant-derived natural products: A review

2015

Draw Science

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Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product- Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a "screening hit" through a "drug lead" to a "marketed drug" is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis.While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.

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Polyphenols Can Inhibit Furin In Vitro As A Result of the Reactivity of their Auto-oxidation Products to Proteins

Abstract: the combined use of detergent and glutathione in the screening assay for furin inhibitors improves the predictive value.

Cited by 13 publications

References 0 publications

Oxidative Stress Type Influences the Properties of Antioxidants Containing Polyphenols in RINm5F Beta Cells

Oxidative Stress Type Influences the Properties of Antioxidants Containing Polyphenols in RINm5F Beta Cells

Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19

Discovery and resupply of pharmacologically active plant-derived natural products: A review

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