functional foods vs supplements
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Natural ingredients as Natural ingredients as Functional Foods vs. Functional Foods vs.
supplementssupplementsMarco Valussi
EHTPA
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Reconciliation Reconciliation
2. Traditional insights on medicinal plants (MPs) and functional foods (FFs): polypharmacology
1. Classical pharmacology: mono-target
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Classical Classical pharmacologypharmacology
Although a minor part of the MPs diversity (1%), heroic plants monopolized early research.
Digitalis spp., Strophanthus spp., Convallaria majalis, Papaver somniferum, Nicotiana spp., Amanita muscaria,
FFs and MPs are just vessels for diluted "drugs”.
Erlich’s “silver bullet”: one gene, one target, one molecule
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ProblemsProblems
Health benefits of FFs decrease as we move towards isolated supplements: see antioxidants.
The attempt to isolate a single molecule/mechanism for MPs has often failed failed: see Hypericum, Ginkgo, Allium, Crataegus, etc.
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ProblemsProblemsMany of modern drugs are promiscuous or pleiotropic
Polypharmacology: AIDS, infections, diabetes, cancer, asthma, depression, cholesterol, etc.
New “silver bullets”: high attrition rates (high toxicity, low efficacy) in phase II and III trials
Chronic diseases are better described as involving a complex network of molecules and interactions.
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FFs act through mixtures of different compounds and modes of action: “herbal shotgun”
1. Evolutionary bases
2. Hormesis/xenohormesis
3. Synergy
4. Network pharmacology
A new positionA new position
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Evolutionary basesEvolutionary basesPlants: many low activity compounds rather than few very active ones: this favors synergy.
Evolutionary continuity: conserved receptorial and signaling systems between Phyla
Adaptive advantage: plants' stress signals are clues to environmental trends and dangers.
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Hormesis/Hormesis/XenohormesisXenohormesis
Toxic molecules detoxified and read by the organisms as triggers for defense reactions: hormesis.
Plants’ stress signals trigger a change: diverting metabolic energy from reproduction and growth to extended life-span and survival: xenohormesis
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Joint action of two or more molecules.
Effect greater than that obtained with single molecules in equivalent quantity.
Effects that could not be obtained with any safe quantity of either molecule.
SynergySynergy
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SynergySynergy1. Weakly targeting proteins in the same
network
2. Acting on targets in different networks
3. Pharmacokinetic synergy
4. Protection of active substance from degradation
5. Circumvention of MDR mechanisms
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Some diseases are described as network of multiple interactions: gene-gene, gene-protein, and protein-protein.
Robust phenotype
Modeling: multiple weak ligands disrupt a network like or better than single strong ligands, with lesser undesirable effects.
Network Network pharmacologypharmacology
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MoleculesMoleculesAlkaloids: toxic extreme, MPs. Activity based on similarities between insects and human CNS.
Terpenoids: middle ground, MPs and FFs. Effects depend on similarities between insects and humans and between plants and humans
Phenolics: benign extreme, MPs and FFs. Effects almost totally dependent on plant-human similarities.
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Lipid-lowering effects
Anti-inflammatory effects
Antioxidant effects
Detoxifying effects
Anti microbial effects
Antiproliferative
FFs and phenolicsFFs and phenolics
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Fruits and vegetables vs. Fruits and vegetables vs. antioxidant supplementsantioxidant supplements
Discrepancy between epidemiology, in vitro and RCTs
1.Synergy and stereoisomery
2.Bad kinetics
3.Bioavailability and intestinal flora
4.Xenohormesis
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Plant Components Effects
Allium sativum Allicin, ajoene, diallyl trisulfide, 2-vinyl-4H-1,3-dithiin
Inhibition iNOS synthase and platelet aggregation, antioxidant, anti-inflammatory, ajoene apoptosis leukemia cells, hypocholesterolemic, anti microbial.
Aronia melanocarpa
Phenolic compounds Phenolic effects: antioxidant; anti-inflammatory; cancer; aging; diabetes; neurodegenerative disorders; renal diseases
Camellia sinensis Catechins, sesquiterpenes, indoles
Catechins: iron chelators, scavengers, anti-inflammatory, neuroprotectants, PKC and MAPK signaling; MDR inhibitors.
Curcuma longa Curcuminoids Cancer; liver cirrhosis; chronic renal disease; COPD; diabetes; AD; Chron’s Disease
Lactuca sativa Ascorbate, a-tocopherol, phenolic compounds
Common cold; phenolic effects
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Plant Components Effects
Opuntia ficus-indica
Betalains Diabetes; dyslipidemia; gastritis; prostate hypertrophy
Punica granatum Polyphenols The juice shows evidence of anti proliferation activity compared to isolated polyphenols
Ribes nigrum Phenolic compounds Phenolic effects
Urtica dioica fol. Caffeic acids derivatives and oxylipin
Inhibition of COX and cytosine. Arthritis and RA
Vitis vinifera Phenolic compounds Phenolic effects
Zingiber officinale
A-zingiberene, b-sesquiphellandrene, bisabolene, curcumene
Very different effects of total extract compared to individual components. Antipyretic, anti-inflammatory, analgesic.
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Thank you for your attention.