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 “ 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
GROUPS
Body Weight
Liver Weight on Day 28
Day 1
Day 28 I
163 ± 4
164 ± 3
3.4 ± 0.3 II
165 ± 3
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,
Arthur, M.J.P., Matrix degradation in liver and a role in injury and repair. Hepatalogy 26,
Ohuchi, E., Imai, E., Fijii, Y., Membrane type I matrix metalloproteinases digests interstitial collagens and other extra cellular matrix macromolecules.J.Biol.Chem.272,
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