Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry

Chang, Chia-Wen; Leu, Yan-Lii; Horng, Jim-Tong

doi:10.3390/v4040539

Cited by 24 publications

(23 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genkwa Flos were extracted with methanol and then concentrated to give brown syrup. The syrup was partitioned first in CHCl 3 /water (1:1) and then in n-butanol/water (1:1) [16]. The cytotoxic effects of the fractionated extracts on lung cancer cells A549 were investigated by treating the cells with extracted compounds at 30 µg/mL for 48 h and the cell viability was determined by MTT assay.…”

Section: Isolation and Identification Of Flavonoids From Genkwa Flosmentioning

confidence: 99%

See 1 more Smart Citation

Hydroxygenkwanin Suppresses Non-Small Cell Lung Cancer Progression by Enhancing EGFR Degradation

Leu

Wang

et al. 2020

Molecules

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC), which is the major type of lung cancer. The EGFR tyrosine kinase inhibitors (TKIs) are the approved treatment for patients harboring activating mutations in the EGFR kinase. However, most of the patients treated with EGFR-TKIs developed resistance. Therefore, the development of compounds exhibiting unique antitumor activities might help to improve the management of NSCLC patients. The total flavonoids from Daphne genkwa Sieb. et Zucc. have been shown to contain antitumor activity. Here, we have isolated a novel flavonoid hydroxygenkwanin (HGK) that displays selective cytotoxic effects on all of the NSCLC cells tested. In this study, we employed NSCLC cells harboring EGFR mutations and xenograft mouse model to examine the antitumor activity of HGK on TKI-resistant NSCLC cells. The results showed that HGK suppressed cancer cell viability both in vitro and in vivo. Whole-transcriptome analysis suggests that EGFR is a potential upstream regulator that is involved in the gene expression changes affected by HGK. In support of this analysis, we presented evidence that HGK reduced the level of EGFR and inhibited several EGFR-downstream signalings. These results suggest that the antitumor activity of HGK against TKI-resistant NSCLC cells acts by enhancing the degradation of EGFR.

show abstract

Section: Isolation and Identification Of Flavonoids From Genkwa Flosmentioning

confidence: 99%

“…A voucher specimen (No. CGU-DG-1) was deposited in the herbarium of Chang Gung University, Taoyuan, Taiwan [16]. The extraction of dried buds of Daphne genkwa Sieb.…”

Section: Plant Materials and Extractionmentioning

confidence: 99%

Hydroxygenkwanin Suppresses Non-Small Cell Lung Cancer Progression by Enhancing EGFR Degradation

Leu

Wang

et al. 2020

Molecules

View full text Add to dashboard Cite

show abstract

“…15 After incubation for 72 h, the medium was removed and the cells were stained with 0.1% Crystal Violet. IC 50 was defined as the concentration of chemical that could inhibit the virus-induced CPE by 50%.…”

Section: Cell Culture Viruses and Viral Infectionmentioning

confidence: 99%

“…15 Briefly, precooled HFF cells were incubated with E2 (containing 9 TCID 50 of virus) along with 2-fold serially diluted PR66 (0.5 -500 nM). The inhibition of viral attachment was indicated by the degree of virus-induced CPE.…”

Section: Viral Attachment Assaymentioning

confidence: 99%

See 1 more Smart Citation

In vitroandin vivostudies of a potent capsid-binding inhibitor of enterovirus 71

Chern

Hsieh

et al. 2016

J. Antimicrob. Chemother.

Self Cite

View full text Add to dashboard Cite

Objectives: Enterovirus 71 (EV-A71) is an important pathogen that can cause severe neurological symptoms and even death. Our aim was to identify potent anti-EV-A71 compounds and study their underlying mechanisms and in vivo activity. Methods:We identified a potent imidazolidinone derivative (abbreviated to PR66) as an inhibitor of EV-A71 infection from the screening of compounds and subsequent structure-based modification. Time-course treatments and resistant virus selection of PR66 were employed to study the mode of mechanism of PR66. In vivo activity of PR66 was tested in the ICR strain of new-born mice challenged with EV-A71/4643/MP4.Results: PR66 could impede the uncoating process during viral infection via interaction with capsid protein VP1, as shown by a resistant virus selection assay. Using site-directed mutagenesis, we confirmed that a change from valine to phenylalanine in the 179th amino acid residue of the cDNA-derived resistant virus resulted in resistance to PR66. PR66 increased the virion stability of WT viruses, but not the PR66-resistant mutant, in a particle stability thermal release assay. We further showed that PR66 had excellent anti-EV-A71 activity in an in vivo mouse model of disease, with a dose-dependent increase in survival rate and in protection against virus-induced hind-limb paralysis following oral or intraperitoneal administration. This was associated with reductions of viral titres in brain and muscle tissues. Conclusions:We demonstrated here for the first time that an imidazolidinone derivative (PR66) could protect against EV-A71-induced neurological symptoms in vivo by suppressing EV-A71 replication. This involved binding to and restricting viral uncoating.

show abstract

Reprotoxicity induced by acute exposure to aqueous tuber extract of Peruvian Maca (Lepidium meyenii Walp.) in Caenorhabditis elegans

Pilissão

Rodrigues

Porto

et al. 2023

J of Applied Toxicology

View full text Add to dashboard Cite

Maca (Lepidium meyenii Walp.) has been used in folk medicine to treat fertility disturbances, a claim that has been evidenced in some studies. However, the clinical trials validating this use have shown paradoxical findings and then maca safety is not well known. This study investigated the effects and mechanisms by which maca affects the reproductive system using an in vivo model, the nematode Caenorhabditis elegans. Tuber maca powder, obtained from local commerce, was used to prepare the aqueous extract. Worms were acutely exposed to maca extracts (40, 120, 240, and 330 μg/μl), and 48 h after treatments, physiological and biochemical assays were conducted. Maca extract caused a significant decrease in total number of eggs and in the number of eggs per worm. These effects were associated to increased lipid peroxidation, reduced triacylglycerol levels, and also impaired vit‐2 (vitellogenin) expression, besides increase in the number of apoptotic germline cells. We have found quantifiable levels of alkaloids in this maca extract, which presence could be related to this toxicity. Collectively, our data suggest that maca extract exposure causes reproductive toxicity to worms that could be, at least in part, associated to both an increase in apoptosis of germline cells and also to a decrease in vitellogenin expression, needed for egg yolk production and, consequently, successful reproduction.

show abstract

Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry

Cited by 24 publications

References 35 publications

Hydroxygenkwanin Suppresses Non-Small Cell Lung Cancer Progression by Enhancing EGFR Degradation

Hydroxygenkwanin Suppresses Non-Small Cell Lung Cancer Progression by Enhancing EGFR Degradation

In vitroandin vivostudies of a potent capsid-binding inhibitor of enterovirus 71

Reprotoxicity induced by acute exposure to aqueous tuber extract of Peruvian Maca (Lepidium meyenii Walp.) in Caenorhabditis elegans

Contact Info

Product

Resources

About