Kim-Hong Gan

Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species.

Twenty-three ursolic acid (1) derivatives 2-24 including nine new 1 derivatives 5, 7-11, 20-22 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell line). Compounds 5 and 17 with an isopropyl ester moiety at C-17-COOH and a succinyl moiety at C-3-OH showed potent inhibitory effect on growth of NTUB1 cells. Compounds 23 and 24 with seco-structures prepared from 1 also showed the increase of the cytotoxicity against NTUB1 cells. Exposure of NTUB1 to 5 (40 microM) and 23 (20 and 50 microM) for 24h significantly increased the production of reactive oxygen species (ROS) while exposure of NTUB1 to 5 (20 and 40 microM) and 23 (20 and 50 microM) for 48 h also significantly increased the production of ROS while exposure of cells to 17 did not increase the amount of ROS. Flow cytometric analysis exhibited that treatment of NTUB1 with 5 or 17 or 23 led to the cell cycle arrest accompanied by an increase in apoptotic cell death after 24 or 48 h. These data suggest that the presentation of G1 phase arrest and apoptosis in 5- and 23-treated NTUB1 for 24 h mediated through increased amount of ROS in cells exposed with 5 and 23, respectively, while the presence of G2/M arrest before accumulation of cells in sub-G1 phase in 5-treated cells for 48 h also due to increased amount of ROS in cells exposed with 5. The inhibition of tubulin polymerization and cell cycle arrest at G2/M following by apoptosis presented in the cell cycle of 23 also mediates through the increase amount of ROS induced by treating NTUB1 with 23 for 48 h.

Flavonol and anthraquinone glycosides from Rhamnus formosana.

Two new flavonol triglycosides, and a new anthraquinone glycoside, have been isolated from the roots of Rhamnus formosana. These compounds have been characterized as rhamnazin 3-O-[alpha-L-rhamopyranosyl(1----4)-alpha-L-rhamnopyranosyl(1----6 )]-beta-D-galactopyranoside (rhamnazin 3-isorhamninoside), rhamnocitrin 3-O-isorhamninoside and 1,6,8-trihydroxy-3-methylanthraquinone 1-O-rhamnosyl(1----2)glucoside, respectively.

New diterpenoids and cytotoxic and anti-inflammatory diterpenoids from Amentotaxus formosana

Two new abietane diterpenoids, ramentoxide (1) and ramentoxidone (2) and a new icetexane diterpenoid, amentonone (3) were isolated from the barks of Amentotaxus formosana. The structures of 1-3 were determined by spectroscopic methods. Known compounds brevitaxin (4), and (+)-ferruginol (5) and ent-kaur-16-en-15-one (6) isolated from this plant revealed potent cytotoxic activity against human breast adenocarcinoma cells, MCF-7 cells with an IC(50) value of 0.08 ± 0.05 μg/mL, and significant anti-inflammatory activities, respectively.

Studies on the Constituents of Formosan Gentianaceous Plants. Part VII Constituents of Swertia Randaiensis Hayata and Pharmacological Activity of Norswertianolin

Bellidifolin (XI) was first isolated from the fresh whole plant of Swertia randaiensis Hayata (Gentianaceae). Further, oleanolic acid, a constituent of this plant, reported by Wu et al, wasreinvestigated by C NMR spectroscopy, being revised into ursolic acid. Pharmacological studies on the xanthone glycoside, norswerianolin, which was previously isolated from this plant, showed that it posseses a depressant activity on the central nervous system.

Rivaroxaban in preventing venous thromboembolism after arthroplastic surgery in Taiwan

Venous thromboembolism (VTE) is one of the severe complications of total hip arthroplasty (THA) and total knee arthroplasty (TKA). The incidence of VTE could be reduced if preventive antithrombotic medicines are used; however, the incidence of bleeding may increase. Rivaroxaban is a factor Xa inhibitor that prevents VTE after THA or TKA. This study is designed to confirm the efficacy and safety of rivaroxaban in Taiwan. This is a retrospective database study based on the data of 6996 patients provided by the Taiwan National Health Insurance Research Database from 2008 to 2012. The data included the number of prescription, the cost of prescription, and case number for patients treated with antithrombotic agents for the prevention or treatment of joint arthroplasty complications (including THA, TKA, partial hip arthroplasty, revision THA and TKA), and the incidence of thrombosis and hemorrhage from year 2008 to 2012. The overall postoperative VTE rate was 0.49%. Compared with other antithrombotic drugs, rivaroxaban and heparin analogs can reduce the percentage of thrombosis. We also found that the expenditure and hospitalization was less in the rivaroxaban group than in the heparin analogs group. Because some benefits of rivaroxaban were found in our study, further cost‐effective and drug safety studies are warranted. It is important to consider the cost‐effective principle for the use of antithrombotic drugs in preventing thromboembolic complications after total joint arthroplasty.