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

Corominas-Faja B, Santangelo E, Cuyàs E, Micol V, Joven J, Ariza X, Segura-Carretero A, García J, Menendez JA - Aging (Albany NY) (2014)

Bottom Line: We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents.PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities.Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

View Article: PubMed Central - PubMed

Affiliation: Metabolism and Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Girona, Spain. Girona Biomedical Research Institute (IDIBGI), Girona, Spain.

ABSTRACT
Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

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Related in: MedlinePlus

Contributions of particular atoms to the gerosuppressant activities of OA and DOAFigures provides a detailed comparison of the atomic groups that are likely to be responsible for the differences (blue circles) in the predictions of antioxidant, anti-inflammatory, antineoplastic, and apoptosis agonist activities with a Pa > 0.4 obtained for the hemiacetalic closed forms of OA and DOA that are not predicted (Pa < 0.2) for the dialdehydic open forms of OA and DOA.
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Figure 4: Contributions of particular atoms to the gerosuppressant activities of OA and DOAFigures provides a detailed comparison of the atomic groups that are likely to be responsible for the differences (blue circles) in the predictions of antioxidant, anti-inflammatory, antineoplastic, and apoptosis agonist activities with a Pa > 0.4 obtained for the hemiacetalic closed forms of OA and DOA that are not predicted (Pa < 0.2) for the dialdehydic open forms of OA and DOA.

Mentions: To preliminarily elucidate hypothesis-generating structural requirements of gerosuppressant oleuropeins, we assessed how the naturally occurring chemical structures of OA and DOA (i.e., the hemiacetalic closed forms versus dialdehydic open forms) impact some anti-aging/anti-cancer-related effects predicted with probabilities of Pa > 0.500 by PASS (i.e., among the top 10 pharmacological effects predicted for each polyphenol isomeric form). Some of the pharma-cological effects assumed to be closely related to the previously reported anti-aging and anti-cancer effects of OA and DOA (i.e., anti-oxidant, anti-inflammatory, and anti-neoplastic effects) are exclusively restricted to the hemiacetalic cyclic forms of OA and DOA (Fig. 4). The apoptosis agonist effect is predicted to occur with a notably higher probability in the cyclic hemiacetalic form of DOA (Pa = 0.610) than in the cyclic hemiacetalic form of OA (Pa = 0.419). Fig. 4 allows assessment of the impact of particular atoms on particular activities of the oleuropein isomers (green indicates a “positive impact”, blue a “neutral impact”, and red a “negative impact”). As green-colored atoms reflect a positive impact on a given activity while the red-colored atoms reflect a negative impact on the same activity, it should be noted that the chemopreventive mechanisms of action that are significantly predicted for the open dialdehydic forms of OA and DOA, but not for their cyclic hemiacetalic isomers mostly involve all of the atoms involved in the polyphenolic structure of DOA. Remarkably, as observed for many drugs with potential antineoplastic and chemopreventive properties, including curcumin and resveratrol [44-50], the open dialdehydic forms of OA and DOA are predicted to exhibit teratogenic and embryotoxic properties.


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

Corominas-Faja B, Santangelo E, Cuyàs E, Micol V, Joven J, Ariza X, Segura-Carretero A, García J, Menendez JA - Aging (Albany NY) (2014)

Contributions of particular atoms to the gerosuppressant activities of OA and DOAFigures provides a detailed comparison of the atomic groups that are likely to be responsible for the differences (blue circles) in the predictions of antioxidant, anti-inflammatory, antineoplastic, and apoptosis agonist activities with a Pa > 0.4 obtained for the hemiacetalic closed forms of OA and DOA that are not predicted (Pa < 0.2) for the dialdehydic open forms of OA and DOA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221918&req=5

Figure 4: Contributions of particular atoms to the gerosuppressant activities of OA and DOAFigures provides a detailed comparison of the atomic groups that are likely to be responsible for the differences (blue circles) in the predictions of antioxidant, anti-inflammatory, antineoplastic, and apoptosis agonist activities with a Pa > 0.4 obtained for the hemiacetalic closed forms of OA and DOA that are not predicted (Pa < 0.2) for the dialdehydic open forms of OA and DOA.
Mentions: To preliminarily elucidate hypothesis-generating structural requirements of gerosuppressant oleuropeins, we assessed how the naturally occurring chemical structures of OA and DOA (i.e., the hemiacetalic closed forms versus dialdehydic open forms) impact some anti-aging/anti-cancer-related effects predicted with probabilities of Pa > 0.500 by PASS (i.e., among the top 10 pharmacological effects predicted for each polyphenol isomeric form). Some of the pharma-cological effects assumed to be closely related to the previously reported anti-aging and anti-cancer effects of OA and DOA (i.e., anti-oxidant, anti-inflammatory, and anti-neoplastic effects) are exclusively restricted to the hemiacetalic cyclic forms of OA and DOA (Fig. 4). The apoptosis agonist effect is predicted to occur with a notably higher probability in the cyclic hemiacetalic form of DOA (Pa = 0.610) than in the cyclic hemiacetalic form of OA (Pa = 0.419). Fig. 4 allows assessment of the impact of particular atoms on particular activities of the oleuropein isomers (green indicates a “positive impact”, blue a “neutral impact”, and red a “negative impact”). As green-colored atoms reflect a positive impact on a given activity while the red-colored atoms reflect a negative impact on the same activity, it should be noted that the chemopreventive mechanisms of action that are significantly predicted for the open dialdehydic forms of OA and DOA, but not for their cyclic hemiacetalic isomers mostly involve all of the atoms involved in the polyphenolic structure of DOA. Remarkably, as observed for many drugs with potential antineoplastic and chemopreventive properties, including curcumin and resveratrol [44-50], the open dialdehydic forms of OA and DOA are predicted to exhibit teratogenic and embryotoxic properties.

Bottom Line: We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents.PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities.Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

View Article: PubMed Central - PubMed

Affiliation: Metabolism and Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Girona, Spain. Girona Biomedical Research Institute (IDIBGI), Girona, Spain.

ABSTRACT
Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

Show MeSH
Related in: MedlinePlus