Turmeric Curcumin Inhibits Entry of All Hepatitis

Turmeric curcumin inhibits entry of all hepatitis c virus
genotypes into human liver cells
PD Dr. Eike Steinmann
Centre for Experimental and Clinical Infection Research
Department of Experimental Virology, Twincore*
*joint venture between Medical School Hannover and Helmholtz Centre for Infection Research
HCV entry into hepatocytes: targets for antiviral therapy
- virus neutralization
- attachment inhibitors
- entry inhibitors
- fusion inhibitors
What and why Curcumin?
• Curcumin is inexpensive and easy to find
(turmeric or kurkuma has 1-2% curcumin content)
• Documented to have a wide spectrum of biological and pharmacological activities
(antioxidant, anti-inflammatory, anticarcinogenic, etc)
• Ethnopharmacologically known to protect liver against cirrhosis
(through suppressing fibrosis and liver inflammation)
• Curcumin is considered safe even at high doses
(based on various animal and human studies)
• Until 2013, NIH has registered 77 clinical trials to study the use of dietary curcumin
100
100
10
H77c/1a/R2a
J4/1b/R2a
JcR2a
S52/3a/R2a
ED43/4a/R2a
SA13/5a/R2a
HK6a/6a/R2a
QC69/7a/R2a
1
0.1
0
5
10
10
1
15
20
Log10 cell viability (% of DMSO)
Log10 infection (% of DMSO)
Curcumin inhibits the infection of all HCV genotypes
25
Curcumin (μM)
+ DMSO
+ DMSO
+ Curcumin 20 µM
H77c/1a
SA13/5a
J6/2a
(Jc1)
HK6a/6a
S52/3a
QC69/7a
ED43/4a
TNcc
(Gt 1a)
+ Curcumin 20 µM
DAPI NS5A
Curcumin treatment does not affect the expression of essential HCV receptors
hCD81
hSR-BI
% of Max
Secondary only
+ DMSO
+ Curcumin 10 μM
+ Curcumin 20 μM
Hep56.1D
hOccludin
hNPC1L1
hClaudin-1
β-actin
β-actin
DMSO 10
20 Hep56.1D
Curcumin
(μM)
DMSO
10
20 Hep56.1D
Curcumin
(μM)
The mode of action of curcumin
Log10 infection rate (% of DMSO control)
-4h
0h
4h
8h
1000
precopost
100
10
1
Control
5
10
Curcumin (μM)
20
The mode of action of curcumin
+/- Curcumin or
JFH1-DPH THC
JFH1-R18
Attachment
Membrane fluidity of the virus
(A)
+/- Curcumin or
THC
(B)
5% FBS:
IC50, 13.3 +/- 5.7 μM
Fusion
(C)
Serum-free:
IC50, 18.2 +/- 5.0 μM
Curcumin is effective in combination with commonly used HCV inhibitors
Jc1 reporter
virus
+ Curcumin
+ PEG-IFNa,
Boceprevir or CsA
Huh7.5
In vivo study of curcumin
In vivo study of curcumin
(A) The effect of no-treatment control, carrier (3% EtOH), and normal curcumin
(20 mg/kg dissolved in carrier) against HCV-CRE infection in Rosa26-Fluc
mice.
Nano-formulated curcumin
Summary
• Curcumin inhibits HCV infection as an entry inhibitor
• Curcumin inhibits the entry of all HCV genotypes
• All curcumin derivates found in curcuminoids have the same potency in inhibiting HCV entry
• The α,β-unsaturated ketone group in curcumin is important for the antiviral activity
• Curcumin acts by preventing the virus attachment and fusion, while also inhibits cell-to-cell
transmission
• The combination treatment of curcumin and other HCV therapy promotes better HCV
clearance in cell culture
• Optimization for in vivo application
Acknowledgement
Twincore
Institute of Experimental Virology
Thomas Pietschmann
Cooperation partners
Luis Schang, Che Colpitts
Michael Ott
Dorothea Bankwitz
Stephanie Pfänder
Philip Meuleman
Patrick Behrendt
Stephanie Walter
Alexander Ploss, Charles Rice
Richard Brown
Juliane Dörrbecker
Heni Rachmawati
Janina Bruening
Mandy Doepke
Anne Frentzen
Gisa Gerold
Corinne Ginkel
Christina Grethe
Sabine Giese
Sibylle Haid
Kathrin Hüging
Angga Kusuma
Paula Perin
Nina Riebesehl
Gabrielle Vieyres
Kathrin Welsch