| Summary: | 碩士 === 元培科技大學 === 放射技術研究所 === 100 === Tithonia diversifolia (Hemsl) A. Gray (Compositae) is commonly referred to as Mexican sunflower, or tree marigold. Pharmacological studies of Tithonia diversifolia showed that it has anti-diabetic, anti-malarial, anti-inflammatory, analgesic, and cancer chemo-preventive activity. They are particularly rich in sesquiterpenoids and flavonoids and these sesquiterpenoids were evaluated for their potential as cancer chemo-preventive agents in cell culture. Tagitinin C, a major sesquiterpenoid, was isolated from the leaves of Tithonia diversifolia. We have identified the anti-hepatoma of tagitinin C in our lab. Our thesis has two parts: One is to study the anti-metastatic activity of tagitinin C in xenograft models of hepatocellular carcinoma (HCC). The other is to study the toxicology of Tithonia diversifolia ethanolic extracts (TDE) at high dose in animal model.
At first, tagitinin C was isolated from TDE. The hepatoma Hep G2 and Huh 7 cells were treated with tagitinin C and assessed for viability by MTT assay, for migration by scratch migration assay and matrix metalloproteinases (MMP) activity assay, for metastasis assay in vivo study by MR techniques and Magnetic Resonance Spectroscopy (MRS) in tumorigenisity of xenografts inoculated by Hep G2 and Huh 7 cells. Tagitinin C was found to have cytotoxic activities against Hep G2 and Huh 7 with IC50 values at 2.0±0.1µg/ml and 1.2±0.1µg/ml individually. tagitinin C resulted in anti-migration and MMP activity decrease which suggested that this compound was anti-metastatic effect in vitro. Moreover, the tumorigenisity of xenografts derived from Hep G2 and Huh 7 cells were probably retarded and anti-migrated by the delivery of tagitinin C (15 μg/mouse/day) relative to the control counterparts by MRS assay. The conclusion in our first part of thesis is that tagitinin C demonstrated antitumor and antimetastatic activities in HCC xenograft model inoculated by two human hepatoma cells. This study provides an auxiliary or alternative therapy for clinical investigation in patients with HCC.
The second part is toxicological test: TDE were administered orally to male Sprague-Dawley rats at various dosages (0, 100, 300, 500 mg/ kg B. W., orally, 5 days/wk, 3 weeks). The animals were validated to have fatty liver compared to the control group (olive oil vehicle, per day, 3 weeks). A common finding in drug safety studies is fatty liver, which is the result of diet, stress, or compounds that modify lipid metabolism in the liver. Fatty liver will gradually develop into a very serious liver disease, such as cirrhosis, fulminant hepatitis, or HCC. With the increasing use of MRI for toxicological studies, this method should provide an improved, noninvasive method of identifying and monitoring individuals with fatty liver.
By use of MR techniques, including Dixon and MRS method, important results of the second study are: (i) the changes of fat content in rat liver after TDE treatment via MRS was time dependent at the dosage of 300 mg/kg, and this result was verified by oil-red stain in pathological observation. (ii) additional finding was that the fat content decreased after 3 weeks TDE treatment at the dose of 300 ～ 500 mg/kg, and this result may be associated with fibrosis in Masson stain.
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