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ANTI FIBROTIC POTENTIAL OF NONI. Liver Fibrosis. Liver Fibrosis is Characterized by Excessive Scarring Excessive Production and deposition of Collagens (elastin and laminin) 3. Decreased Collagenolytic activity (1) 4. Altered Extra cellular matrix ( ECM ).

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ANTI FIBROTIC POTENTIAL OF NONI


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    1. ANTI FIBROTIC POTENTIAL OF NONI

    2. Liver Fibrosis • Liver Fibrosis is Characterized by • Excessive Scarring • Excessive Production and deposition of Collagens • (elastin and laminin) • 3. Decreased Collagenolytic activity (1) • 4. Altered Extra cellular matrix ( ECM )

    3. Biochemical Marker Hydroxy Proline ( HP) Altered ECM – Major producer of fibrotic neomatrix Altered ECM – excess collagen - Triple Helix structure Stabilized by Hydroxy Proline

    4. Altered ECM Degraded by Matrix Metallo Proteinase (MMP) 2 & 3 Inhibited by Tissue Inhibitors of MMP ( TIMPS) In fibrosis Excessive Production of TIMPS TIMPS expression correlates with HP

    5. INDUCTION Liver fibrosis – results of repeated repair of chronic liver damage. Chronic Liver injury – chemicals – CCl4. Single dose – Liver Damage Repeated doses – Chronic Liver damage.

    6. Materials and Methods Animals - Male Albino Wistar rats Groups I - Normal II - CCL4 -1 ml/kg mixed with equal volume of liquid paraffin twice a week for 4 weeks (4) III - “ + 5 ml of diluted Noni extract in divided doses.

    7. Biochemical Parameters Aspartate Transaminase (AST – IU/L) Alanine Transaminase (ALT – IU/L) Alkaline Phosphatase ( ALP – IU/L) Total Bilirubin (TBL – mg/dl) Hydroxyproline (HP – mg/g of liver) Other Parameters Body Weight Liver Weight

    8. Effect of Noni on biochemical Parameter AST ( IU/L) ALT ( IU/L) ALP ( IU/L) TBL (mg/dl) HP (μg/g of liver tissue) GROUPS Groups I 159 ± 6 47 ± 2 215 ± 7 0.48 ± .01 53 ± 3 II 289 ± 11* 102 ± 5* 396 ± 8* 1.6 ± .08* 124 ± 7* III 175 ± 8*a 61 ± 4*a 235 ± 12*a 0.7 ± 0.3*a 77 ± 3*a • Significantly different from Group –I • *a Significantly different from Group - II

    9. Effect of Noni on liver and Body weight Body Weight GROUPS Liver Weight on Day 28 Day 28 Day 1 I 163 ± 4 3.4 ± 0.3 164 ± 3 165 ± 3 II 148±2* 4.5 ±0.06* 3.8 ± 0.05*a III 164 ± 2 159 ±2*a • Significantly different from Group –I • *a Significantly different from Group - II

    10. DISCUSSION • Hepatic stellate cells of Liver are associated with fibrosis • Normally – Vit A stores • Chronic injury – proliferation Excessive secretion of collagen Altered ECM HP

    11. Level of HP correlates with the extent of fibrosis • Scope for future study • CCL4  CCL3 (free radical)  Lipid peroxidation Liver damage • Antioxidant potential  confirms the antifibrotic potential

    12. CONCLUSION • AST, ALT, ALP, TBL levels confirm the hepato protective potential • HP level in group III indicate the antifibrotic potential of NONI

    13. references • Okazaki, I., Maruyama, K.,1974. Collagenase activity in experimental hepatic fibrosis. Nature 252, 49-50. • Arthur, M.J.P., 1997. Matrix degradation in liver and a role in injury and repair. Hepatalogy 26, 1069-1071. • Ohuchi, E., Imai, E., Fijii, Y., 1997. Membrane type I matrix metalloproteinases digests interstitial collagens and other extra cellular matrix macromolecules.J.Biol.Chem.272,2446-2451. • Bickel, M., Baader, E., Brocks, D.G., Engelbart, K., Gunzler, V., Schmidts, H.L., Vogel, G.H., 1991.Beneficial effects of inhibitors of propyl 4-hydroxylase in CCl4 induced fibrosis of liver in rats.J.Hepatol.13 (Suppl.3),26-33.

    14. THANKING YOU