Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and...

20
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 Sargowo 1,2 , Hendarto 1 , M. Saifur Rohman 2 1

Transcript of Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and...

Page 1: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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

Page 2: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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

Page 3: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

Karatzis EN. Hell J Cardiol 2005; 46: 232-239

The Role of Inflammatory Agents in Endothelial Function and their Contribution to Atherosclerosis

3

Page 4: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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?

Page 5: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

Objective

• To examine whether mangosteen’s pericarp inhibit NF- κB activation, IL-6 and ICAM-1 expression in high cholesterol diet rats

Page 6: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

6

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

Page 7: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

RESULTS

Page 8: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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

Page 9: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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

Page 10: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

NF-кB Activation

One way ANOVA, Post Hoc analysis

Page 11: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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

Page 12: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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

Page 13: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

ICAM-1 Expression

One way ANOVA, Post Hoc analysis

Page 14: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

Il-6 Protein Level

Data Transformation, One way ANOVA, Post Hoc analysis

Page 15: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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

Page 16: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

• 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

Page 17: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

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

Page 18: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

18

Page 19: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

19

Page 20: Pericarp of Mangosteen Inhibits Nuclear Factor κ B (NF- κ B) Activation and Reduces ICAM-1 and IL-6 in Atherosclerosis Department of Cardiology, Brawijaya.

20