ANTI FIBROTIC POTENTIAL OF NONI

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ANTI FIBROTIC POTENTIAL OF NONI
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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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Biochemical Marker Hydroxy Proline ( HP)
Altered ECM Major producer of fibrotic neomatrix
Altered ECM excess collagen -
Triple Helix structure
Stabilized by
Hydroxy Proline
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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
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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.
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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.
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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
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Effect of Noni on biochemical Parameter
AST ( IU/L)
ALT ( IU/L)
TBL (mg/dl)
ALP ( IU/L)
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 8a
61 4a
235 12a
0.7 0.3a
77 3a

• Significantly different from Group I
• a Significantly different from Group - II

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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
1482
4.5 0.06
3.8 0.05a
III
164 2
159 2a

• Significantly different from Group I
• a Significantly different from Group - II

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DISCUSSION

• Hepatic stellate cells of Liver are associated
  with fibrosis
• Normally Vit A stores
• Chronic injury proliferation

Excessive secretion of collagen
Altered ECM
HP
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• 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

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CONCLUSION

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

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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.

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