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 Medical School Saiful Anwar General Hospital Djanggan Sargowo 1,2, Hendarto 1, M. Saifur Rohman 2 1

2. 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 2

3. Karatzis EN. Hell J Cardiol 2005; 46: 232-239 The Role of Inflammatory Agents in Endothelial Function and their Contribution to Atherosclerosis 3

4. 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? 4

5. Objective To examine whether mangosteens pericarp inhibit NF- κB activation, IL-6 and ICAM-1 expression in high cholesterol diet rats 5

6. 6 Simple Random sampling Rattus novergicus wistar strain divided into 5 treatment groups Group I Normal diet Group IIGroup III Group IVGroup V Blood sample and aortic arch tissue were examined at week 12 th Immunohistochemistry staining of NF-κB & ICAM-1 or IL-6 protein by ELISA methods To 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

7. RESULTS 7

8. NF -κ B Activation Normal diet (Negative Control) High cholesterol diet (Positive Control) the arrows indicate brown discoloration in the cell nucleus p = 0.000 Immunohistochemistry staining, magnification 200x 8

9. High cholesterol diet + Mangosteens pericarp Extract 200 mg/kg NF- κ B Activation High cholesterol diet + Mangosteens pericarp Extract 400 mg/kg High cholesterol diet + Mangosteens pericarp Extract 800 mg/kg the arrows indicate brown discoloration in the cell nucleus Immunohistochemistry staining, magnification 200x 9

10. NF- к B Activation One way ANOVA, Post Hoc analysis 10

11. High cholesterol diet (Positive Control) Normal diet (Negative Control) ICAM-1 Expression arrows show brown discoloration in the cytoplasm p = 0.000 Immunohistochemistry staining, magnification 200x 11

12. ICAM-1 Expression High cholesterol diet + Mangosteens pericarp Extract 200 mg/kg High cholesterol diet + Mangosteens pericarp Extract 400 mg/kg High cholesterol diet + Mangosteens pericarp Extract 800 mg/kg arrows show brown discoloration in the cytoplasm Immunohistochemistry staining, magnification 200x 12

13. ICAM-1 Expression One way ANOVA, Post Hoc analysis 13

14. Il-6 Protein Level Data Transformation, One way ANOVA, Post Hoc analysis 14

15. 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- к B 1 Mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in vitro system 2 1.Nakatani, et al Mol Pharmacol. 2004 Sep;66(3):667-74 2.Williams P, et al Free Radic Res. 1995 Aug; 23(2): 175-84 15

16. 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 rats 2 α -Mangostin, i.p. has anti-inflammatory effects in several experimental models of inflammation in rats and guinea pigs 3 1.Madan B et al Bioorg Med Chem 2002;10:3431–3436 2.Devi Sampath and Vijayaraghavan 2007 3.Gopalakrishnan et al.1980 16

17. CONCLUSION High cholesterol diet group resulted in significantly increased NF- к B activation, ICAM-1 expression 400 and 800 mg/kg pericarp extract inhibited NF- к B 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 17

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