Salacia (S.) reticulata, a Hippocrateaceae plant distributed in Sri Lankan and Indian forests, has been used as a supplementary food in Japan to prevent obesity and diabetes. We examined the antiobesity effects of the hot water-soluble extract (SRHW) from the roots of S. reticulata using obese rat models and an in vitro study. Body weight (P = 0.07) and periuterine fat storage (P = 0.10) in female Zucker fatty rats (8-9 wk old) tended to be suppressed by oral administration of SRHW (125 mg/kg) for 27 d. Male rats fed a high fat diet were not affected by SRHW. Furthermore, SRHW inhibited porcine pancreatic lipase (PL), rat adipose tissue-derived lipoprotein lipase (LPL) and glycerophosphate dehydrogenase (GPDH) activities with 50% inhibitory concentrations (IC(50)) of 264 (95% confidence limits: 203-393) mg/L, 15 (12-18) mg/L and 54 (35-85) mg/L, respectively, but did not inhibit hormone-sensitive lipase activity in rat adipose tissue. Next, we examined the effects of polyphenols, di- and triterpenes and salacinol isolated from the roots of S. reticulata on lipid metabolizing enzymes and lipolysis. (-)-Epigallocatechin and (-)-epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin inhibited PL activity with IC(50) of 88 (not calculated) and 68 (26-122) mg/L, respectively. (-)-Epicatechin, 3beta, 22beta-dihydroxyolean-12-en-29-oic acid and the tannin fraction inhibited LPL activity with IC(50) of 81 (54-214), 89 (62-214) and 35 (24-62) mg/L. Only the tannin fraction inhibited GPDH activity with an IC(50) of 6.8 (3.4-10.9) mg/L. These constituents may be involved in the lipase and GPDH inhibitory activities of SRHW. On the other hand, SRHW at 100 mg/L tended to enhance lipolysis in rat adipocytes (P = 0.06). Significant lipolytic effects were exerted by mangiferin, (-)-4'-O-methylepigallocatechin and maytenfolic acid at 100 mg/L (P < 0.01). In conclusion, polyphenolic compounds may be involved in the antiobesity effects of SRHW in rats through inhibition of fat metabolizing enzymes (PL, LPL and GPDH) and enhanced lipolysis.

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Drugs for cancer chemotherapy generally have severe side effects, therefore, drug delivery systems that enable delivery of such drugs solely to tumor tissues are awaited. Liposomes are thought to be an ideal drug carrier, since they can encapsulate both hydrophilic and hydrophobic materials, and are biodegradable and essentially non-toxic. Liposomal encapsulation of drugs has been shown to enhance drug efficacy and to reduce side effects. Liposomes are especially suitable for delivery of anti-cancer agents, since liposomes have a tendency to passively accumulate in tumor tissues due to the leaky nature of the vascular endothelium of these tissues.

Most anti-cancer agents express not only primary therapeutic effects but also unfavorable side effects because of their low tumor-selectivity. To improve this problem, a drug delivery system (DDS) which enables delivery of a certain agent to the target organ is being used in cancer chemotherapy. Liposomes have been used as carriers of anti-cancer agents, since they can effectively deliver the entrapped materials to the interstitial spaces of tumor tissue of which blood vessels are highly permeable. Furthermore, the liposomal surface can be modified with certain targeting molecules such as antibodies and peptides, and they are expected to be used as active targeting tools.1) In fact, liposomalization of anti-tumor agents has been studied extensively and shown to increase their plasma concentration, to improve their distribution, and to decrease the side effects. 2,3) In this study, we investigated the anti-tumor efficacy of 6-[[2-(dimethylamino) ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103), a novel quinoline derivative, in a liposomal formulation. TAS-103 is known to show high and broad anti-tumor activity against murine and human tumor cells by inhibiting both topoisomerase I and II activity. [4][5][6] Like other cytotoxic anti-tumor drugs, improvement in the tumor selective delivery of the agent may make it beneficial for the practical use. For this reason, we encapsulated TAS-103 into liposomes and evaluated the antitumor efficacy of liposomal TAS-103. MATERIALS AND METHODSMaterials TAS-103 is the product of Taiho Pharmaceutical Co., Ltd. (Tokushima, Japan). Dipalmitoylphosphatidylcholine (DPPC) was a gift from Nippon Fine Chemical Co. Ltd. (Takasago, Hyogo, Japan). Cholesterol was purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.), and reduced Triton X-100 was from Aldrich Chemical Co. (Milwaukee, WI, U.S.A.).Preparation of Liposomal TAS-103 DPPC and cholesterol (2 : 1 as a molar ratio) dissolved in chloroform were dried under reduced pressure and stored in vacuo for at least 1 h to prepare thin lipid film. Liposomes were formed by hydration with 0.3 M citric acid solution adjusted to pH 4.0, frozen and thawed for three cycles using liquid nitrogen, and sonicated in a bath-type sonicator for 10 min. The resulting liposomes were sized by three extrusions through a polycarbonate membrane filter with a pore size of 100-nm. TAS-103 encapsulation was performed as described previously. 7)Briefly, liposomal solution was neutralized with 0.5 M sodium carbonate and diluted with 20 mM HEPES-buffered saline, pH 7.5, to establish a pH gradient between inner and outer solutions of liposomes. Then, the liposomes were incubated with 20 mM HEPES-buffered TAS-103 solution at 60°C for 30 min to load TAS-103 into the internal aqueous space of liposomes. Liposomal TAS-103 solution was ultracentrifuged thrice at 90000ϫg for 15 min to remove any untrapped TAS-103 if present. Then, the liposomal TAS-103 was resuspended in phosphate-buffered saline (PBS), pH 7.4. For the evaluation of encaps...