Department of Cardiology , Brawijaya Medical School Saiful Anwar General Hospital

1. Pericarp of Mangosteen Inhibits Nuclear Factor κB (NF-κB) Activation and Reduces ICAM-1’ and IL-6in Atherosclerosis DjangganSargowo1,2, Hendarto1, M. Saifur Rohman2 • Department of Cardiology, Brawijaya Medical School • Saiful Anwar General Hospital

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

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

4. Model for the role of NF-κB/Reltranscription factors in atherogenesis Pericarp of mangosteen? Brand K, Page S, et al. Experimental Physiology 1997; 82: 297-304

5. Objective • To examine whether mangosteen’spericarp inhibit NF- κBactivation, IL-6 and ICAM-1 expression in high cholesterol diet rats

6. Methods Simple Random sampling Rattusnovergicuswistar strain divided into 5 treatment groups High cholesterol diet Group I Normal diet GroupII GroupIII GroupIV GroupV Mangosteen peel extract 200mg/kg (po) Mangosteen peel extract 400 mg/kg (po) Mangosteen peel extract 800 mg/kg (po) Blood sample and aortic arch tissue were examined at week 12th 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

7. RESULTS

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

9. NF-κB Activation High cholesterol diet + Mangosteen’spericarp Extract 200 mg/kg the arrows indicate brown discoloration in the cell nucleus the arrows indicate brown discoloration in the cell nucleus High cholesterol diet + Mangosteen’spericarp Extract 400 mg/kg the arrows indicate brown discoloration in the cell nucleus High cholesterol diet + Mangosteen’spericarp Extract 800 mg/kg Immunohistochemistry staining, magnification 200x

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

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

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

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

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

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-кB1 • Mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in vitro system2 Nakatani, et al Mol Pharmacol. 2004 Sep;66(3):667-74 Williams P, et al Free Radic Res. 1995 Aug; 23(2): 175-84

16. Xanthones significantly inhibit TNF-α-induced increase of ICAM-1 expression in cultured endothelial cells1 • 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 Madan B et al Bioorg Med Chem 2002;10:3431–3436 Devi Sampath and Vijayaraghavan 2007 Gopalakrishnan et al.1980

17. 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

20. Thank You