The ground dried rhizome of the plant, Curcuma longa LINN has long been used as a naturally occurring medicine for the treatment of inflammatory and other diseases, and has also been used as a coloring agent and spice in many foods. 1)The powdered rhizome is commonly called turmeric. Curcumin (diferuloylmethane) is a major active ingredient that has been identified as the major pigment in turmeric. Curcumin is well known as a potent anti-oxidant, 2,3) and recent studies have revealed that it is a potent inhibitor of reactive oxygen-generating enzymes, such as lipoxygenase/cyclooxygenase, 4,5) xanthine dehydrogenase/oxidase 6) and inducible nitric oxide synthase 7) and it possesses anti-inflammatory activity. 8,9) Moreover, it has shown anti-carcinogenic activity in animal models, such as colon tumor initiation by azoxymethane 10) and skin tumor promotion induced by phorbol ester TPA.11) Recently, curcumin has been considered by oncologists as a potential third generation cancer chemopreventive agent, and clinical trials using it have been carried out in several laboratories.Leishmania such as Leishmania major are the protozoan parasite responsible for leishmaniasis. So far, medicines used for the treatment of leishmaniasis such as pentavalent antimonials and pentamidine are toxic or have severe side effects, for example renal, cardiac and neural toxicity, shock and risk of diabetes.12) Other medicines such as amphotericin B are restricted to hospital use. In addition, resistance towards these medicines have been observed. 13) Thus, the development of a new agent is urgently needed.During the search for the candidate of anti-parasitic agents from natural resources, we have found that curcumin has leishmanicidal activity in vitro. MATERIALS AND METHODSChemicals Curcumin was purchased from Funakoshi Co., Ltd. (Tokyo, Japan) and other chemicals used were special grade.Axenic Cultivation of Leishmania The medium used for the cultivation of promastigotes of L. major (MHOM/ SU/73/5ASKH) was SDM-79, previously described by Brun and Schonenberger.14) Leishmania were cultured into 25 cm 2 -tissue culture flasks containing 5 ml of culture medium per flask and maintained therein at 27°C in an atmosphere of 5% CO 2 -95% air.Leishmanicidal Assay Cultured leishmania of promastigotes were centrifuged at 600 g for 5 min at 4°C, and the parasites then resuspended with culture medium, diluted to a density of 5ϫ10 5 /ml and inoculated into 96-well plate. The medium (0.1 ml) containing various concentrations of curcumin dissolved in dimethyl sulfoxide (DMSO) was added into each well and incubated at 27°C in an atmosphere of 5% CO 2 -95% air. The final concentration of DMSO was 0.5%. After incubation for an appropriate period, the number of surviving leishmania was determined microscopically by counting in a Burker-Turk hemocytometer. The leishmanicidal activity of curcumin was shown as 50% growth inhibitory concentration (GI 50 ), 100% growth inhibitory concentration (TGI) and LD 50 after incubation with leishmania for 24 h. 100% gr...

Structural transformation of arctiin and tracheloside, major components of seeds of Arctium lappa and Carthamus tinctorius, were investigated using rat gastric juice (pH 1.2-1.5) and rat large intestinal flora in vitro. Quantitative analysis of lignans and their metabolites was carried out by high performance liquid chromatography. Both lignans were stable in rat gastric juice and arctiin was rapidly transformed to arctigenin in rat large intestinal flora, followed by conversion to the major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-butyrolactone. On the other hand, tracheloside also decreased dependently with time and was converted to trachelogenin and its major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-2-hydroxybutyrola ctone. These experiments suggest that in the course of metabolism of lignans, firstly a cleavage of the glycosidic bond occurred and then demethylation of the phenolic methoxy group in the alimentary tract followed.

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A comparison of antihepatotoxic activities between glycyrrhizin (18 beta-GL) and its genuine aglycone, glycyrrhetinic acid (18 beta-GA), was carried out using in vivo and in vitro assay methods. The oral administration of 18 beta-GA at 1, 24, and 48 h before D-galactosamine (GalN) treatment significantly reduced the increase of serum transaminase activities 24 h after GalN treatment, whereas 18 beta-GL did not inhibit the increase of serum transaminase activities. The intraperitoneal administration of 18 beta-GA 1 h before GalN treatment restored the increase of serum transaminase activities with lower doses than 18 beta-GL. In CCl4-induced cytotoxicity of primary cultured rat hepatocytes, 18 beta-GA protected the CCl4-induced leakage of transaminase at doses of 5 to 50 micrograms/ml, whereas 18 beta-GL inhibited slightly the leakage at a dose of 1000 micrograms/ml. In the same way, 18 alpha-GA, the alpha-isomer of 18 beta-GA, reduced the CCl4-induced cytotoxicity more strongly than 18 alpha-GL. Furthermore, the adsorbability of 18 alpha, beta-GA on primary cultured rat hepatocytes was higher than that of 18 alpha, beta-GL. These results suggest that 18 alpha, beta-GA is a more potent antihepatotoxic agent than 18 alpha, beta-GL, and that the potency of the antihepatotoxic compounds parallels their adsorbability in hepatocytes.