« from enhancement of bioactivity to enhancer biology di 7 aprile/3-d'alessio.pdf · •...
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International Congress Ostheopatic Medicine
Florence 3-6 April, 2011
© copyright 2011 by Patrizia d’Alessio Prof University Paris Sud-11
www.aisa-tx.com
« From enhancement of bioactivity
to enhancer biology »
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Aristoteles (384 - 322 a. C.) Problemata,
XXX,« La ragione, la mente, la sapienza »
• 8. Perché il lavoro dei medici finisce col raggiungimento della
salute ?…Ridanno la salute e a questo punto si fermano.
• Forse perché non é possible che da questa condizione ne
derivi un’altra ?
• Oppure, se é possibile, sarà compito di un’altra scienza, e
quello che si riuscirà a fare a partire dalla salute sarà
qualcosa di diverso?
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Enhancers
• Definition
• « enhancer » is a region of DNA (regulatory sequence)
that can fix proteins to stimulate gene transcription. The
gene and the enhancer are not necessarily close to each
other and may be on two different chromosomes BUT the
DNA repliement in the nucleus allows them a physical
proximity.
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Enhancement of bioactivity
• Some examples:
• Terpenes, such as d-Limonene and menthone induce
bio-physical changes in the stratum corneum (SC)
lipids of the skin, allowing « chemical penetration »
and « percutaneous absorbtion » (i.e. enhancement
of permeability coefficient of an active principle).
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Visible surface
Kindly provided by Pr Guimberteau
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Surfaces and physical dynamics
• Albert Szent-Gyorgy formulated (1945-57) that thick
layers of interfacial water lie on the surfaces of bio-
molecules and induce physical dynamics
giving rise to electron excitation.
• Should the enhancer activity interfere with the basic
dynamics occurring at the interface (surface) between
bio-molecules and their hydration shell?
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To meet an « enhancer »
• Cytoprotective anti-inflammatory actives
• Multiple effects of one molecule
• Trying to understand
• Role of CAM
• Nutrition
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STRESS
2002 Endothelium as pharmacological target. P. D’Alessio, Curr. Op. Invest. Drugs, 1720-1724
2003 Aging and the endothelium. P. D’Alessio, Journal of Experimental Gerontology, 165-171
Inflammation accelerates the appearance
of markers associated with cell senescence
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CNRS « ICSN »
CHINA « Academy Medical
Sciences »
Cell Biology
Bio-guided selection
Pharmacokinetics Toxicity studies
Proofs
3 Patents
Applications
in vivo
Pre-clinical
studies
Phase I
in vitro
“Hits”
“Leads”
Candidates
Molecules
Platform
Selection by a Screening Platform
2008 New pharmaceutical interventions in aging. P. D’Alessio Rejuvenation Research 11, 399-407
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Bio-guided selection permitted to identify 4 AISA out of
2000 tested molecules from some 100 plant extracts
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but also found in breast milk,
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Three (main) different effects
• Inflammation
• Mood disorders
• Tissue repair
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AISA 5203-L inhibition of ICAM-1
following stimulation by TNF-α (HUVEC)
P1 P3 P9
% i
nh
ibit
ion
Inhibition of cell adhesion, a new
mechanism of anti-inflammation
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TNF-
serum
levels
are
lowered
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The senescent phenotype is reversible
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TPA / Hairless skin SHK-mice model used for the study of inflammatory and auto-immune diseases Medeiros R, Otuki MF, Avellar MC, Calixto JB Eur J Pharmacol 2006
TISSUE REPAIR
control TPA Lim + TPA
POH + TPA
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Pain and mood modulation
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Assessement of the link between
mood and physical alterations • Depressive symptoms and mood alterations increasing with age are now
recognized to be relevant to the development of atherosclerosis.
•Stress is changing also physical parameters
• Enhancers modifying biological surface properties could be interesting in
preservation and restoration of function, diminishing the impact of inflammatory
chronic disease.
Fasciatherapy combined with Pulsology induces changes in blood turbulence
potentially beneficial for the Endothelium. Queré N, Noel E, Lieutaud A,
and d'Alessio P. J Bodyw Mov Ther. 2009 13(3) : 239-45
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Enhancer molecule out of food as a potential
anti-inflammatory device :
1/ Nutraceutical intervention
2/ Culinary education
3/ Physical activity
4/ Posturology
5/ Spiritual activity
6/ Meditation
Consciousness through Mouvement
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As Lifespan becomes longer
the quality of life becomes important :
health is the key.
As slight physical displacements such as experienced
during Feldenkrais or induced by fascia or osteopathic
manipulations could,
as diet, act as enhancers of specific molecular effects
contained in food components
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« Correspondances »
« La Nature est un temple …
• L'homme y passe à travers des forêts de symboles…
• Dans une ténébreuse et profonde unité,…
• Les parfums, les couleurs et les sons se
confondent…
• riches et triomphants,
Ayant l'expansion des choses infinies,
Comme l'ambre, le musc, le benjoin et l'encens,
Qui chantent les transports de l'esprit et des sens. »
(C. Baudelaire)
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