| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 92 === Toona sinensis (TS) is a broadleaf tree. The leaves and young shoots have been used as a vegetable in China for thousands of years. The leaves and stems of this plant have been used for the treatment of enteritis, dysentery and itch in oriental medicine. Recently, aqueous leaf extracts of TS was used as a folk medicine for lowering blood sugar and blood pressure.
In present study, the leaves extracts of TS on CCl4-induced acute hepatotoxicity were invegtigated, we found TS possessed a significant dose-dependent decline effect on serum SGOT and SGPT levels promotion. Our data have indicated that HBV transfected human hepatoma cells (2.2.15 cells) cultured with different dose of TS (0.01-1.0 mg/ml) showed a significant effect on decreasing the secretion of HBsAg and HBeAg into culture medium of 2.2.15 cell.
We also observed that TS aquous extract (TS) possessed inhibitory effect on tumor cell proliferation (HepG2 cells). Our results have indicated the cytotoxic effect of leaf extracts on various cancer cell lines with MTT and methylene blue colormetric method. The IC50 of TS on hepatoma (HepG2 cells) are 0.53±0.04 mg/ml, 0.52±0.01 mg/ml, separately.
In situ detection of fragmented DNA (TUNEL assay) demonstrated that 0.1 mg/ml casused a more significant effect of HepG2 cells different dosage, TS (0.01-1.0 mg/ml) have in the increased of DNA fragmentation.
The apoptotic signal on membrane TNF-R1 and its ligand TNF-α both were augment by addiation of TS (0.01-1.0 mg/ml).
Nitric oxide (NO) is a muti-regulated molecule in hepatocyte, NO can inhibit the main mediators of cell death include caspase, protease. TS-induced the increase of the intracellular NO level and the when high NO concentration may lead to the formation of toxic reaction products like dinitrogen or peroxynitrite that consequment induced cell apoptosis.
Cyclin GMP produced in response to nitric oxide may regulate the celll proliferation and apoptosis by through phosphorylation of cGMP-dependent protein kinase and realated gene expression. TS decreased the intracellular c-GMP level may be through the inhibition of guanylate cyclase. Meanwhile, TS (0.1 mg/ml) also activated the apoptosis routes final stage effector caspase-3.
In conclusion, our data have indicated that TS is potential as a hepatoprotective, antiviral and antihepatoma new drug and the anticancer mechanism may be through the increase synthase of NO, activation of caspase-3 and decrease of the intracellular cGMP.
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