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Bioinform Biol Insights
2023 Jan 01;17:11779322221149613. doi: 10.1177/11779322221149613.
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Antioxidant and Anti-inflammatory Activity of Sea Cucumber (Holothuria scabra) Active Compounds against KEAP1 and iNOS Protein.
Wargasetia TL
,
Ratnawati H
,
Widodo N
,
Widyananda MH
.
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Oxidative stress and inflammation have a role in the development of various diseases. Oxidative stress and inflammation are associated with many proteins, including Kelch ECH associating protein 1 (KEAP1) and inducible nitric oxide synthase (iNOS) proteins. The active compounds contained in Holothuria scabra have antioxidant and anti-inflammatory properties. This study aimed to evaluate the antioxidant and anti-inflammatory activity of sea cucumber's active compounds by targeting KEAP1 and iNOS proteins. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging activity of H. scabra extract were measured spectrophotometrically. The 3-dimensional (3D) structures of sea cucumber's active compounds and proteins were obtained from the PubChem and Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) databases. Molecular docking was performed using AutoDock Vina software. Molecular dynamics simulations were carried out using Yet Another Scientific Artificial Reality Application (YASARA) software with environmental parameters according to the cell's physiological conditions. The membrane permeability test was performed using the PerMM web server. The methanol extract of H. scabra had a weak antioxidant activity against DPPH and strong activity against NO radical. Scabraside and holothurinoside G had the most negative binding affinity values when interacting with the active site of KEAP1 and iNOS proteins. Molecular dynamics simulations also showed that both compounds were stable when interacting with KEAP1 and iNOS. However, scabraside and holothurinoside G were difficult to penetrate the cell plasma membrane, which is seen from the high energy transfer value in the lipid acyl chain region of phospholipids. Scabraside and holothurinoside G are predicted to act as antioxidants and anti-inflammations, but in their implementation to in vitro and in vivo study, it is necessary to have liposomes or nanoparticles, or other delivery methods to help these 2 compounds enter the cell.
Alderton,
GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo.
2005, Pubmed
Alderton,
GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo.
2005,
Pubmed
Assawasuparerk,
Scabraside D Derived from Sea Cucumber Induces Apoptosis and Inhibits Metastasis via iNOS and STAT-3 Expression in Human Cholangiocarcinoma Xenografts.
2016,
Pubmed
,
Echinobase
Bloodsworth,
Nitric oxide regulation of free radical- and enzyme-mediated lipid and lipoprotein oxidation.
2000,
Pubmed
Bondia-Pons,
Oxidative stress and inflammation interactions in human obesity.
2012,
Pubmed
Canning,
Structural basis of Keap1 interactions with Nrf2.
2015,
Pubmed
Chatterjee,
GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury.
2003,
Pubmed
Chen,
Principal component analysis of binding energies for single-point mutants of hT2R16 bound to an agonist correlate with experimental mutant cell response.
2015,
Pubmed
Cinelli,
Inducible nitric oxide synthase: Regulation, structure, and inhibition.
2020,
Pubmed
Cuadrado,
Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases.
2019,
Pubmed
Dakrory,
Protective and curative effects of the sea cucumber Holothuria atra extract against DMBA-induced hepatorenal diseases in rats.
2015,
Pubmed
,
Echinobase
Fischmann,
Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation.
1999,
Pubmed
Gallorini,
The Selective Acetamidine-Based iNOS Inhibitor CM544 Reduces Glioma Cell Proliferation by Enhancing PARP-1 Cleavage In Vitro.
2019,
Pubmed
Heightman,
Structure-Activity and Structure-Conformation Relationships of Aryl Propionic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1/Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1/NRF2) Protein-Protein Interaction.
2019,
Pubmed
Hämäläinen,
Inhibition of iNOS expression and NO production by anti-inflammatory steroids. Reversal by histone deacetylase inhibitors.
2008,
Pubmed
Kansanen,
The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer.
2013,
Pubmed
Kareh,
Anti-proliferative and anti-inflammatory activities of the sea cucumber Holothuria polii aqueous extract.
2018,
Pubmed
,
Echinobase
Karimi,
Herbal versus synthetic drugs; beliefs and facts.
2015,
Pubmed
Katsuoka,
Genetic evidence that small maf proteins are essential for the activation of antioxidant response element-dependent genes.
2005,
Pubmed
Khotimchenko,
Pharmacological Potential of Sea Cucumbers.
2018,
Pubmed
,
Echinobase
Korhonen,
Nitric oxide production and signaling in inflammation.
2005,
Pubmed
Krieger,
YASARA View - molecular graphics for all devices - from smartphones to workstations.
2014,
Pubmed
Kumar,
Antimicrobial Peptide Designing and Optimization Employing Large-Scale Flexibility Analysis of Protein-Peptide Fragments.
2019,
Pubmed
Lo,
Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling.
2006,
Pubmed
Lobanov,
[Radius of gyration is indicator of compactness of protein structure].
2008,
Pubmed
Lomize,
Physics-Based Method for Modeling Passive Membrane Permeability and Translocation Pathways of Bioactive Molecules.
2019,
Pubmed
Martínez,
Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis.
2015,
Pubmed
Mitu,
Evidence for a Saponin Biosynthesis Pathway in the Body Wall of the Commercially Significant Sea Cucumber Holothuria scabra.
2017,
Pubmed
,
Echinobase
Mohammadizadeh,
Evaluation of antibacterial, antifungal and cytotoxic effects of Holothuria scabra from the North Coast of the Persian Gulf.
2013,
Pubmed
,
Echinobase
Mou,
Recent progress in Keap1-Nrf2 protein-protein interaction inhibitors.
2020,
Pubmed
Nakazawa,
iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53.
2017,
Pubmed
Netea,
A guiding map for inflammation.
2017,
Pubmed
O'Boyle,
Open Babel: An open chemical toolbox.
2011,
Pubmed
Olivera-Castillo,
A Glycosaminoglycan-Rich Fraction from Sea Cucumber Isostichopus badionotus Has Potent Anti-Inflammatory Properties In Vitro and In Vivo.
2020,
Pubmed
,
Echinobase
Pace,
Contribution of hydrogen bonds to protein stability.
2014,
Pubmed
Phongpaichit,
Biological activities of extracts from endophytic fungi isolated from Garcinia plants.
2007,
Pubmed
Pranweerapaiboon,
An ethyl-acetate fraction of Holothuria scabra modulates inflammation in vitro through inhibiting the production of nitric oxide and pro-inflammatory cytokines via NF-κB and JNK pathways.
2020,
Pubmed
,
Echinobase
Pranweerapaiboon,
Methanolic Extract from Sea Cucumber, Holothuria scabra, Induces Apoptosis and Suppresses Metastasis of PC3 Prostate Cancer Cells Modulated by MAPK Signaling Pathway.
2021,
Pubmed
,
Echinobase
Robledinos-Antón,
Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development.
2019,
Pubmed
Ru,
Cancer Cell Inhibiting Sea Cucumber (Holothuria leucospilota) Protein as a Novel Anti-Cancer Drug.
2022,
Pubmed
,
Echinobase
Shekh-Ahmad,
KEAP1 inhibition is neuroprotective and suppresses the development of epilepsy.
2018,
Pubmed
Tong,
Different electrostatic potentials define ETGE and DLG motifs as hinge and latch in oxidative stress response.
2007,
Pubmed
Trott,
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.
2010,
Pubmed
Wakabayashi,
Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation.
2003,
Pubmed
Wang,
The potential roles of Nrf2/Keap1 signaling in anticancer drug interactions.
2021,
Pubmed
Ďuračková,
Some current insights into oxidative stress.
2010,
Pubmed