Toxicity evaluation of Eleutherine plicata Herb. extracts and possible cell death mechanism

Gomes, Antônio Rafael Quadros; Galucio, Natasha Costa da Rocha; Albuquerque, Kelly Cristina Oliveira de; Brígido, Heliton Patrick Cordovil; Varela, Everton Luiz Pompeu; Castro, Ana Laura Gadelha; Vale, Valdicley Vieira; Bahia, Marcelo de Oliveira; Burbano, Rommel Rodrı́guez; Molfeta, Fábio Alberto de; Carneiro, Liliane Almeida; Percário, Sandro; Dolabela, Maria Fâni

doi:10.1016/j.toxrep.2021.07.015

Cited by 9 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest the cytotoxicity of EEEp and FDMEp are related to the synergism between eleutherin and isoeleutherin compounds. When administered together they are more active, which may increase toxicity ( Vale et al, 2020 ; Gomes et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, using peritoneal macrophages from BALB/c mice, the cytotoxic activity of EEEp, its fractions (FDEp, FAEp and FMEp) and isoeleutherin were evaluated, with no cytotoxicity being observed. Gomes et al (2021), evaluated the cytotoxicity of EEEp, FDMEp and isoeleutherin from E. plicata in human hepatoma cells (HepG2), after exposure for 24 h, and observed that fractionation reduced cytotoxicity, with isoeleutherin being the least toxic sample. These results suggest the cytotoxicity of EEEp and FDMEp are related to the synergism between eleutherin and isoeleutherin compounds.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Anti-leishmanial activity of Eleutherine plicata Herb. and predictions of isoeleutherin and its analogues

Albuquerque,

Veiga,

Silveira

et al. 2024

Front. Chem.

Self Cite

View full text Add to dashboard Cite

Introduction: Leishmaniasis is caused by protozoa of the genus Leishmania, classified as tegumentary and visceral. The disease treatment is still a serious problem, due to the toxic effects of available drugs, the costly treatment and reports of parasitic resistance, making the search for therapeutic alternatives urgent. This study assessed the in vitro anti-leishmanial potential of the extract, fractions, and isoeleutherin from Eleutherine plicata, as well as the in silico interactions of isoeleutherin and its analogs with Trypanothione Reductase (TR), in addition to predicting pharmacokinetic parameters.Methods: From the ethanolic extract of E. plicata (EEEp) the dichloromethane fraction (FDEp) was obtained, and isoeleutherin isolated. All samples were tested against promastigotes, and parasite viability was evaluated. Isoeleutherin analogues were selected based on similarity in databases (ZINK and eMolecules) to verify the impact on structural change.Results and Discussion: The extract and its fractions were not active against the promastigote form (IC50 > 200 μg/mL), while isoeleutherin was active (IC50 = 25 μg/mL). All analogues have high intestinal absorption (HIA), cell permeability was moderate in Caco2 and low to moderate in MDCK. Structural changes interfered with plasma protein binding and blood-brain barrier permeability. Regarding metabolism, all molecules appear to be CYP3A4 metabolized and inhibited 2–3 CYPs. Molecular docking and molecular dynamics assessed the interactions between the most stable configurations of isoeleutherin, analogue compound 17, and quinacrine (control drug). Molecular dynamics simulations demonstrated stability and favorable interactions with TR. In summary, fractionation contributed to antileishmanial activity and isoleutherin seems to be promising. Structural alterations did not contribute to improve pharmacokinetic aspects and analogue 17 proved to be more promising than isoeleutherin, presenting better stabilization in TR.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Anti-leishmanial activity of Eleutherine plicata Herb. and predictions of isoeleutherin and its analogues

Albuquerque,

Veiga,

Silveira

et al. 2024

Front. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the subacute toxicity assay, EEEp and FDMEp also did not cause clinical, hematological, or biochemical changes. Moreover, isoeleutherine, eleutherine, and eleutherol ( Figure 1 ) bound similarly to caspase-8 [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Participation of Oxidative Stress in the Activity of Compounds Isolated from Eleutherine plicata Herb

et al. 2023

Self Cite

View full text Add to dashboard Cite

From Eleutherine plicata, naphthoquinones, isoeleutherine, and eleutherol were isolated, and previous studies have reported the antioxidant activity of these metabolites. The present work evaluated the role of oxidative changes in mice infected with Plasmodium berghei and treated with E. plicata extract, fraction, and isolated compounds, as well as to verify possible oxidative changes induced by these treatments. E. plicata extracts were prepared from powder from the bulbs, which were submitted to maceration with ethanol, yielding the extract (EEEp), which was fractionated under reflux, and the dichloromethane fraction (FDMEp) was submitted for further fractionation, leading to the isolation of isoeleutherine, eleutherine, and eleutherol. The antimalarial activity was examined using the suppressive test, evaluating the following parameters of oxidative stress: trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH). Furthermore, the molecular docking of naphthoquinones, eleutherol, eleutherine, and isoeleutherine interactions with antioxidant defense enzymes was investigated, which was favorable for the formation of the receptor–ligand complex, according to the re-rank score values. Eleutherine and isoeleutherine are the ones with the lowest binding energy for catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx1), showing themselves as possible targets of these molecules in the involvement of redox balance. Data from the present study showed that treatments with E. plicata stimulated an increase in antioxidant capacity and a reduction in oxidative stress in mice infected with P. berghei, with naphthoquinones being responsible for reducing oxidative changes and disease severity.

show abstract

“…Urb.) has antibacterial potential (Padhi dan Panda, 2015;Munaeni et al, 2019;Novaryatiin et al, 2019) and provide natural antioxidant properties (Haerani et al, 2019;Shi et al, 2019;Munaeni et al, 2020a;Gomes et al, 2021). Bioactive compounds of Dayak onion contain naphthalene, naphthoquinone, anthraquinone (Insanu et al, 2014), flavonoid, saponin, tannin, steroid, dan triterpenoid (Munaeni et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Effect of Dayak Onion (Eleutherine bulbosa (Mill.) Urb.) on the Immune Response and Gene Expression of Nile Tilapia (Oreochromis niloticus) Infected with Aeromonas hydrophila

Fauzi,

Yuhana,

Widanarni

et al. 2023

JIPK

View full text Add to dashboard Cite

Dayak onion (Eleutherine bulbosa (Mill.) Urb.) has the potential to be an immunostimulant to benefit fish health. This study aimed to evaluate the effectiveness of dietary supplementation with the powder and crude ethanol extracts of Dayak onion on the hematology and immune response parameters of Nile tilapia challenged with Aeromonas hydrophila. The research used a completely randomized design with six treatments and three replications. Nile tilapias were fed with Dayak onion (w/v) consisting of powders of 5% (P5), 10% (P10), and 15% (P15), while crude extract was 0.5% (E05) and given during rearing for 30 days. Positive control (C+) and negative control (C-) were used without Dayak onion. Nile tilapia in treatment C+, P5, P10, and P15 were injected with A. hydrophila 10⁶ CFU mL⁻1, while that in treatment C- was injected with phosphate buffered saline (PBS) intramuscularly. The results showed that the dietary with 15% powder and 0.5% crude extract significantly improved the hematology and immune response parameters compared to the control after the challenge against A. hydrophila (P<0.05). Dayak onion supplementation effectively increased the health status based on hematology and immune response parameters of Nile tilapia against A. hydrophila infection. Highlight Research Dayak onion has significant potential to improve nonspecific immunity in fish. Dayak onion improves hematology and immune response of Nile tilapia. Dayak onion can significantly regulate the immune system against A. hydrophila infection. Dayak onion significantly increases the production of the gene expression of IL-1β and TNF-α.

show abstract

Toxicity evaluation of Eleutherine plicata Herb. extracts and possible cell death mechanism

Abstract: Graphical abstract

Cited by 9 publications

References 49 publications

Anti-leishmanial activity of Eleutherine plicata Herb. and predictions of isoeleutherin and its analogues

Anti-leishmanial activity of Eleutherine plicata Herb. and predictions of isoeleutherin and its analogues

Participation of Oxidative Stress in the Activity of Compounds Isolated from Eleutherine plicata Herb

Effect of Dayak Onion (Eleutherine bulbosa (Mill.) Urb.) on the Immune Response and Gene Expression of Nile Tilapia (Oreochromis niloticus) Infected with Aeromonas hydrophila

Contact Info

Product

Resources

About