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

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Glycyrrhiza glabra• Used to treat – ulcers– gastritis– cough– longing for sweets

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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.

Does G. glabra have an effect on Aβ aggregation?

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CL2006: thioflavin S staining

- 7 -

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

Can G. glabra reduce Aβ-induced toxicity?

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Paralysis assay in CL4176

• temperature inducible Aβ expression paralysis due to Aβ toxicity

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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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Thank you for your attention!- 13 -

IPMBUniversity of Heidelberg