Effects of liquorice on beta-amyloid aggregation and toxicity
in Caenorhabditis elegansPille Link, Prof. Dr. M. Wink
University of HeidelbergInstitute for Pharmacy and Molecular
Biotechnology
Conflict of interest: nothing to declare
http://www.alz.org/braintour/images/plaques_tangles.jpg
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Alzheimer‘s disease
oxidative stress
inflammation
neuronal cell death
loss of memory
Aβ plaques
antioxidant
anti inflammatory
neuroprotective
memory-enhancingG. glabra?
neurofibrillary tangles
amyloid-β plaques
Asl MN & Hosseinzadeh H (2008). Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds. Phytotherapy Research 22: 709-724.
Caenorhabditis elegans: a model for Alzheimer’s disease
• CL2006– Aβ42 expression in muscle cells
number of plaques
• CL4176– temperature inducible Aβ42 expression in muscle
cells– progressive paralysis
Aβ42 toxicity- 5 -Link CD (2006). C. elegans models of age-associated neurodegenerative diseases: lessons from
transgenic worm models of Alzheimer's disease. Exp Gerontol 41: 1007-1013.
Control
G. glabra GA
GRA ILG GAAGADA
0
20
40
60
80
100
120N
umbe
r of p
laqu
es (%
of c
ontr
ol)
*
G. glabraControl
G. glabra GA
GRA ILG GAAGADA
0
20
40
60
80
100
120N
umbe
r of p
laqu
es (%
of c
ontr
ol)
*
*
G. glabra
Glycyrrhiza glabra
- 8 -* p < 0.01
glycyrrhizic acid (GA)
O
O
OOHOH
OH
OO
OOH
OH
OH OH OOOH
Control
G. glabra
GA GRA ILG GAA GADA0
20
40
60
80
100
120N
umbe
r of p
laqu
es (%
of c
ontr
ol)
*
**
G. glabra
glycyrrhetinic acid (GRA)
OH
OOOH
Control G. glabra
GA GRA ILG GAA GADA0
20
40
60
80
100
120N
umbe
r of p
laqu
es (%
of c
ontr
ol)
*
**
*
G. glabra
O
OH
OH
OH
isoliquiritigenin (ILG)
concentration: 100 µg/ml
Activity against Aβ-toxicity
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24h 26h 28h 30h 32h 34h 36h0
20
40
60
80
100
120
Hours after temperature upshift
control
ILG(50 µg/ml)
24h 26h 28h 30h 32h 34h 36h0
20
40
60
80
100
120
Hours after temperature upshift
% n
ot p
aral
ysed
control
G. glabra(200 µg/ml)
Conclusions & outlook
• extract & pure compounds from G. glabra can: decrease the number of Aβ plaques counteract Aβ toxicity
• most active compound: isoliquiritigenin
• further work: test more compuonds clarify the mode of action
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