Pericarp of Mangosteen Inhibits Nuclear Factor κB (NF-κB) Activation and Reduces

ICAM-1’ and IL-6 in Atherosclerosis

Department of Cardiology, Brawijaya Medical SchoolSaiful 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

Mea

n nu

mbe

r of

NF-

kB E

xpre

ssio

n

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

Mea

n nu

mbe

r of

ICA

M-1

Exp

ress

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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