Post on 30-Mar-2015
Pericarp of Mangosteen Inhibits Nuclear
Factor κB (NF-κB) Activation and Reduces ICAM-1’ and IL-6 in Atherosclerosis
Department of Cardiology, Brawijaya Medical School
Saiful Anwar General Hospital
Djanggan Sargowo1,2, Hendarto1, M. Saifur Rohman2
Background• Atherosclerosis is a major cause of
mortality and morbidity not only in the developed countries but also in developing countries
• Atherosclerosis is widely viewed as an inflammatory disease with hypercholesterolemia being a dominant underlying risk factor
Karatzis EN. Hell J Cardiol 2005; 46: 232-239
The Role of Inflammatory Agents in Endothelial Function and their Contribution to Atherosclerosis
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Model for the role of NF-κB/Rel transcription factors in atherogenesis
Brand K, Page S, et al. Experimental Physiology 1997; 82: 297-304
Pericarp of mangosteen?
Objective
• To examine whether mangosteen’s pericarp inhibit NF- κB activation, IL-6 and ICAM-1 expression in high cholesterol diet rats
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Simple Random sampling
Rattus novergicus wistar strain divided into 5 treatment groups
Group INormal diet
Group II Group III Group IV Group V
Blood sample and aortic arch tissue were examined at week 12th
Immunohistochemistry staining of NF-κB & ICAM-1 or IL-6 protein by ELISA methodsTo examine NF-κB activation, ICAM-1 expression and IL-6 level
Data analysis
Mangosteen peel extract 200mg/kg (po)
Mangosteen peel extract 400 mg/kg (po)
Mangosteen peel extract 800 mg/kg (po)
High cholesterol diet
Methods
RESULTS
NF-κB ActivationNormal diet (Negative Control)
High cholesterol diet (Positive Control)
the arrows indicate brown discoloration in the cell nucleus
the arrows indicate brown discoloration in the cell nucleusNormal diet High cholesterol diet
0
10
20
30
40
50
60
70
80
29.7±6.1
71.8±4.7
NF-κB Activation
Treatment Group
Me
an
nu
mb
er
of
NF
-kB
Ex
pre
ss
ion
p = 0.000
Immunohistochemistry staining, magnification 200x
High cholesterol diet + Mangosteen’s pericarp Extract 200 mg/kg
NF-κB Activation
High cholesterol diet + Mangosteen’s pericarp Extract 400 mg/kg
High cholesterol diet + Mangosteen’s pericarp Extract 800 mg/kg
the arrows indicate brown discoloration in the cell nucleus
the arrows indicate brown discoloration in the cell nucleus
the arrows indicate brown discoloration in the cell nucleus
Immunohistochemistry staining, magnification 200x
NF-кB Activation
One way ANOVA, Post Hoc analysis
High cholesterol diet (Positive Control)
Normal diet (Negative Control)ICAM-1 Expression
arrows show brown discoloration in the cytoplasm
arrows show brown discoloration in the cytoplasm
Normal diet High cholesterol diet
0
10
20
30
40
50
60
20.5 ±3.3
51.3±8.6
ICAM-1 Expression
Treatment Group
Me
an
nu
mb
er
of
ICA
M-1
Ex
pre
ss
ion
p = 0.000
Immunohistochemistry staining, magnification 200x
ICAM-1 Expression
High cholesterol diet + Mangosteen’s pericarp Extract 200 mg/kg
High cholesterol diet + Mangosteen’s pericarp Extract 400 mg/kg
High cholesterol diet + Mangosteen’s pericarp Extract 800 mg/kg
arrows show brown discoloration in the cytoplasm
arrows show brown discoloration in the cytoplasm
arrows show brown discoloration in the cytoplasm
Immunohistochemistry staining, magnification 200x
ICAM-1 Expression
One way ANOVA, Post Hoc analysis
Il-6 Protein Level
Data Transformation, One way ANOVA, Post Hoc analysis
DISCUSSION• γ- Mangostin inhibited COX-1 and -2 activity and
PGE-2 synthesis in C6 rat glioma cells, inhibited LPS-induced expression of COX-2 protein and its mRNA, reduced the LPS-inducible activation of NF-кB1
• Mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in vitro system2
1. Nakatani, et al Mol Pharmacol. 2004 Sep;66(3):667-742. Williams P, et al Free Radic Res. 1995 Aug; 23(2): 175-84
• Xanthones significantly inhibit TNF-α-induced increase of ICAM-1 expression in cultured endothelial cells 1
• Mangostin showed protective effect against isoproterenol-induced oxidative damage and myocardial injury in rats2
• α-Mangostin, i.p. has anti-inflammatory effects in several experimental models of inflammation in rats and guinea pigs3
1. Madan B et al Bioorg Med Chem 2002;10:3431–34362. Devi Sampath and Vijayaraghavan 20073. Gopalakrishnan et al.1980
CONCLUSION• High cholesterol diet group resulted in significantly
increased NF-кB activation, ICAM-1 expression
• 400 and 800 mg/kg pericarp extract inhibited NF-кB activation and reduced ICAM-1 protein expression in high cholesterol rats
• The extract of mangosteen peel significantly inhibits NF-κB activation and reduces ICAM-1 and IL-6 expression in high cholesterol rats
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