[Abstract unavailable

Tumor cells generally proliferate rapidly and the demand for essential nutrients as well as oxygen always exceeds the supply due to the unregulated growth and the insufficient and inappropriate vascular supply. However, cancer cells show an inherent ability to tolerate extreme conditions, such as that characterized by low nutrient and oxygen supply, by modulating their energy metabolism. Thus, targeting nutrientdeprived cancer cells may be a novel strategy in anticancer drug development. Based on that, we established a novel screening method to discover anticancer agents that preferentially inhibit cancer cell viability under the nutrientdeprived condition. After screening 500 medicinal plant extracts used in Japanese Kampo medicine, we found that a CH 2 Cl 2 -soluble extract of Arctium lappa exhibited 100% preferential cytotoxicity under the nutrient-deprived condition at a concentration of 50 Mg/mL with virtually no cytotoxicity under nutrient-rich condition. Further bioassayguided fractionation and isolation led to the isolation of arctigenin as the primary compound responsible for such preferential cytotoxicity; the compound exhibited 100% preferential cytotoxicity against nutrient-deprived cells at a concentration of 0.01 Mg/mL. Furthermore, arctigenin was also found to strongly suppress the PANC-1 tumor growth in nude mice, as well as the growth of several of the tested pancreatic cancer cell lines, suggesting the feasibility of this novel antiausterity approach in cancer therapy. Further investigation of the mechanism of action of arctigenin revealed that the compound blocked the activation of Akt induced by glucose starvation, which is a key process in the tolerance exhibited by cancer cells to glucose starvation.

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Natural products are excellent sources of lead compounds in the search for new medicaments for the treatment of diseases. The largest present underexplored source of such materials lies in tropical and subtropical regions of the world. In these areas, a long tradition of ethnobotanical medicine often exists and offers a rich and relatively untapped source for the discovery of new drugs from natural products. Vietnam, a tropical Southeast Asian country, also has a long history of traditional medicine systems. 1) However, systematic exploitation of these natural resources for their human health benefits has not been carried out to a significant degree.Gout is a common disease with a worldwide distribution. Hyperuricemia, which is associated with gout, results from the overproduction or underexcretion of uric acid and is greatly influenced by a high dietary intake of foods rich in nucleic acids, such as meats (especially organ meats), leguminous seeds, some types of seafood, and food yeasts. 2,3) During the last step of purine metabolism, xanthine oxidase (XO) catalyses the oxidation of xanthine and hypoxanthine into uric acid. 4) Uricosuric drugs which increase the urinary excretion of uric acid, or XO inhibitors which block the terminal step in uric acid biosynthesis, can lower the plasma uric acid concentration, and are generally employed for the treatment of gout.5) Allopurinol is a clinically used XO inhibitor in the treatment of gout, but this drug suffers from many side effects such as hepatitis, nephropathy, and allergic reactions.6) Thus, new alternatives with increased therapeutic activity and less side effects are desired. Moreover, superoxide anion radicals generated by XO are involved in various pathological states such as hepatitis, inflammation, ischemiareperfusion, carcinogenesis, and aging.2,7) Thus, the search for novel XO inhibitors would be beneficial not only to treat gout but also to combat various other diseases.To identify potential XO inhibitory agents from natural sources, we have tested 288 extracts prepared from 96 selected medicinal plants, which are used by the indigenous people in Vietnam for the treatment of gout or diseases associated with symptoms such as rheumatism, arthritis and inflammation. In addition, the active constituents of Chrysanthemum sinense, which showed the most potent XO inhibitory activity, have been determined. Chemicals Xanthine oxidase (EC 1.2.3.2) from bovine milk (10 units/ml) and xanthine were obtained from Sigma Chemical Co. (St. Louis, MO, U.S.A.). Allopurinol was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Other reagents were of the highest grade available. MATERIALS AND METHODS Plant MaterialsPreparation of Samples Each medicinal plant (10-213 g) was cut into small pieces and extracted successively with MeOH (200-300 ml, reflux, 2 h, ϫ3), MeOH-H 2 O (1 : 1, 200-300 ml, reflux, 2 h, ϫ2), and water (200-300 ml, reflux, 2 h). The MeOH solution was evaporated under reduced pressure to give a MeOH extract, while MeOH-H 2 O (1 : 1) and w...

From the MeOH extract of the aerial part of Vietnamese Orthosiphon stamineus, five new isopimarane-type diterpenes [orthosiphols F-J (1-5)] and two new diterpenes [staminols A (6) and B (7)] with a novel carbon-framework, to which we proposed the name "staminane", and three new highly-oxygenated staminane-type diterpenes [staminolactones A (8) and B (9) and norstaminol A (10)1 were isolated. Moreover, staminolactone A (8) is 8,14-secostaminane-type and staminolactone B (9) is 13,14-secostaminane-type, while norstaminol A (10) is 14-norstaminen-type. Together with these new diterpenes, sixteen known compounds were also isolated and identified to be: 7,3',4'-tri-O-methylluteolin (11), eupatorin (12), sinensetin (13), 5-hydroxy-6,7,3',4'-tetramethoxyflavone (14), salvigenin (15), ladanein (16), tetramethylscutellarein (17), 6-hydroxy-5,7,4'-trimethoxyflavone (18), vomifoliol (19), aurantiamide acetate (20), rosmarinic acid (21), caffeic acid (22), oleanolic acid (23), ursolic acid (24), betulinic acid (25), and beta-sitosterol (26). All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the new diterpenes, except for 4, and flavonoids (11, 12, 16, 18) showed cytotoxicity with an ED50 value between 10 and 90 microg/ml.