Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; Garcia, Jordi; Menendez, Javier A.

doi:10.18632/aging.100691

Cited by 26 publications

(32 citation statements)

References 44 publications

(32 reference statements)

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“…Research on mitochondriotropic antioxidants has been increasing over the last years. One viable and promising strategy involves the use of dietary polyphenolic antioxidants templates along with the chemical modulation of their properties, including mitochondrial targeting ability, efficacy, and toxicity 25 . In this context, some mitochondria-targeted polyphenolic-based molecules have been developed including MitoResveratrol, MitoCurcumin, and MitoQuercetin 26–28 .…”

Section: Resultsmentioning

confidence: 99%

Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid

Teixeira

Oliveira

Borges

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN3) based on the dietary antioxidant gallic acid was developed. AntiOxBEN3 accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN3 showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN3 presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN3 strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN3 can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders.

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Section: Resultsmentioning

confidence: 99%

Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid

Teixeira

Oliveira

Borges

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Although molecular dynamics and Austin Model 1 (AM1) level computational mapping of oleuropein have been developed, the downstream mechanisms are not fully understood [ 16 , 17 ]. This is one of the drawbacks of important bioavailable olive BPsecos, their concentration present in olive products, and their biomolecular structures [ 34 ]. Acid-catalyzed oleuropein downstream pathways, however, could evolve via dynamic pre-equilibrium to oleuropein + H + isomers ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Probing Downstream Olive Biophenol Secoiridoids

Sivakumar

Uccella²,

Gentile

2018

IJMS

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Numerous bioactive biophenol secoiridoids (BPsecos) are found in the fruit, leaves, and oil of olives. These BPsecos play important roles in both the taste of food and human health. The main BPseco bioactive from green olive fruits, leaves, and table olives is oleuropein, while olive oil is rich in oleuropein downstream pathway molecules. The aim of this study was to probe olive BPseco downstream molecular pathways that are alike in biological and olive processing systems at different pHs and reaction times. The downstream molecular pathway were analyzed by high performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI/MS) and typed neglected of different overlap (TNDO) computational methods. Our study showed oleuropein highest occupied molecular orbital (HOMO) and HOMO-1 triggered the free radical processes, while HOMO-2 and lowest unoccupied molecular orbital (LUMO) were polar reactions of glucoside and ester groups. Olive BPsecos were found to be stable under acid and base catalylic experiments. Oleuropein aglycone opened to diales and rearranged to hydroxytyrosil-elenolate under strong reaction conditions. The results suggest that competition among olive BPseco HOMOs could induce glucoside hydrolysis during olive milling due to native olive β-glucosidases. The underlined olive BPsecos downstream molecular mechanism herein could provide new insights into the olive milling process to improve BPseco bioactives in olive oil and table olives, which would enhance both the functional food and the nutraceuticals that are produced from olives.

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“…Improved prediction of drug performance prior to lengthy experimentation would cut waste [ 21 , 22 ]. Vast datasets now exist that enable such prediction with the help of sophisticated computational methods [ 23 , 24 ]. Two particularly valuable datasets in this respect are the literally millions of gene expression profiles stored in repositories such as GEO [ 25 , 26 ] and a number of increasingly diverse compound screening libraries [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state

Aliper¹,

Belikov

Garazha

et al. 2016

Aging

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Populations in developed nations throughout the world are rapidly aging, and the search for geroprotectors, or anti-aging interventions, has never been more important. Yet while hundreds of geroprotectors have extended lifespan in animal models, none have yet been approved for widespread use in humans. GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. GeroScope maps expression differences between samples from young and old subjects to aging-related signaling pathways, then profiles pathway activation strength (PAS) for each condition. Known substances are then screened and ranked for those most likely to target differential pathways and mimic the young signalome. Here we used GeroScope and shortlisted ten substances, all of which have lifespan-extending effects in animal models, and tested 6 of them for geroprotective effects in senescent human fibroblast cultures. PD-98059, a highly selective MEK1 inhibitor, showed both life-prolonging and rejuvenating effects. Natural compounds like N-acetyl-L-cysteine, Myricetin and Epigallocatechin gallate also improved several senescence-associated properties and were further investigated with pathway analysis. This work not only highlights several potential geroprotectors for further study, but also serves as a proof-of-concept for GeroScope, Oncofinder and other PAS-based methods in streamlining drug prediction, repurposing and personalized medicine.

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Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins

Cited by 26 publications

References 44 publications

Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid

Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid

Probing Downstream Olive Biophenol Secoiridoids

In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state

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