Determination Of Bioavailability Of Curcumin Solid Dispersion And Protective Effect On Experiental Hepatic Fibrosis In Mice

1.Background: Chronic liver diseases is still in danger with the health of people in our country. In the step of"chronic liver disease-liver fibrosis-liver cirrhosis"which some chronic liver diseases experience,liver fibrosis is in the central step, and it can be reversed. Up to now, we have no effective therapy on liver fibrosis.Curcumin is the polyphenols compound extracted from turmeric. It is the main active component of turmeric. Recent studies have proved that curcumin can play widely roles in pharmacological action. It is effective in anti-oxygenation, anti-inflammation, nor-blood fat, anti- tumor , etc. Because of the hard dissolution in water, little absorption in corpore, quick metabolism, as well as the low bioavailability, curcumin is necessary to be exploited and developed the new dosage form to improve its solubility and to raise its bioavailability, which will provide the experimental evidences for its future development and application.2.Objective and content: Our research aims at discussing protective effect of curcumin solid dispersion on experimental hepatic fibrosis in mice. The experiment here includes two parts: 1) The research on the r oral bioavailability of curcumin solid dispersion in mice .2) Protective effect of curcumin solid dispersion on experimental hepatic fibrosis in mice.3.Method:1) Same doses of the curcumin solid dispersion and curcumin were administrated to two groups of mice, respectively. Then we acquired the blood at different times, to compare the pharmacokinetic(PK) paratemer in the two groups and to further investigate whether or not that curcumin solid dispersion could improve the bioavailability in plasma concentration ; 2) The model of the experimental chronic hepatic fibrosis in mice were induced by CCl4. The mice were divided into five groups : low-dose group of curcumin solid dispersion, high-dose group of the curcumin solid dispersion , normal group, model control group, and positive control group. After treatment, the serumal ALT, AST, HA,C-Ⅳ, TGF-β1,the weight ratio of liver/body, the weight ratio of spleen /body, and the change of hepatic tissue histomorphology were measured to evaluate the protective effect of curcumin solid dispersion on experimental chronic hepatic injury in mice.4. Result: In the curcumin group, the t1/2αwas 1.058 h ,the t1/2βwas 2.568h ,and AUC was 1.903. But in curcumin solid dispersion group , the t1/2αwas 0.457h, t1/2βwas 3.167h, and AUC was 8.028. The results showed that curcumin solid dispersion could raise curcumin bioavailability in mice. Similar to colchine, hige-dose group of the curcumin solid dispersion was shown to significantly inhibit the increase of ALT, AST, HA,C-Ⅳ, TGF-β1, the weight ratio of liver/body, and the weight ratio of spleen /body, as well as lessen liver histopathology change.5. Conclusion: Curcumin solid dispersion could raise curcumin bioavailability in mice and showed protective effect on experimental chronic hepatic liver fibrosis induced in mice by CCl4.