Planta medica
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In a suspension culture of Taxus baccata L. cultivated in a liquid medium according to Ericksson in a 6.21 bioreactor paclitaxel and 8 of its analogues were identified.
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The antimetastatic effects of orally administered ginsenoside Rb1 (Rb1) and an active metabolite by intestinal bacteria, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (I), were studied, by using a spontaneous metastasis model produced by subcutaneous injection of Lewis lung carcinoma (LLC) in syngeneic C57BL/6 mice. A thorough analysis of the hydrolyzing potential (transformation by intestinal bacteria) was first done and the data found were positively correlated to the antimetastatic effect of Rb1 through the medium of I. ⋯ In a leg amputation model with the LLC-line, an effect on survival time of I (8 mg/kg/day) equal to that of 5-FU (10 mg/kg/day) was seen and 38% mice were cured as compared with 13% cured by amputation alone. These findings suggest that the active drug is the bacterial metabolite I which should be administered rather than Rb1.
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Cell culture of Taxus wallichiana Zucc (= T. baccata ssp wallichiana Zucc. Pilg.) (Himalayan yew) has been established and taxol-producing cell lines selected by cell line cloning. Cell line NC110 derived from needle leaf of a 40-year-old tree growing in Darjeeling Himalayas produced 0.018% taxol in B5 basal medium supplemented with 2,4-D (2 mg/l), kinetin (0.5 mg/l), and casein hydrolysate (0.5%). ⋯ Significant enhancement in the level of taxol (0.05%) was obtained in this cell line by supplementation of the basal medium with 5 mg/l of IAA-phenylalanine instead of 2,4-D without adversely affecting cell growth. IAA-glycine also enhanced taxol level (0.03%) while IAA alone (1-10 mg/l) was ineffective in inducing taxol accumulation. Using three different cell lines with different taxol-producing capacities, it has been demonstrated that 2,4-D and IAA-phenylalanine when present alone favour growth and taxol production but when combined enhance biomass to a maximum (six-fold in NC110) without enhancing taxol accumulation, suggesting that a two-stage culture may be beneficial for optimising taxol accumulation in cell culture of T. wallichiana.
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The effects of boldine [(S)-2,9-dihydroxy-1,10-dimethoxyaporphine], a major alkaloid in the leaves and bark of boldo (Peumus boldus Mol.), on skeletal muscle were studied using mouse diaphragm and isolated sarcoplasmic reticulum membrane vesicles. Boldine, at 10-200 microM, has little effect on the muscle-evoked twitches; however, the ryanodine-induced contracture was potentiated dose-dependently. ⋯ Boldine also dose-dependently increased apparent [3H]-ryanodine binding with the EC50 value of 50 microM. In conclusion, we have shown that boldine could sensitize the ryanodine receptor and induce Ca2+ release from the internal Ca2+ storage site of skeletal muscle.
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The potential of intestinal bacteria to hydrolyze ginsenoside Rb1 to 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (I) was found in 79% of the fecal specimens from 58 human subjects whose age ranged from 1 to 64 years. Following a ginsenoside-Rb1-hydrolyzing activity assay, Prevotella oris strains were then isolated as a major bacterial species possessing the potential. ⋯ These results suggest that the metabolism of protopanaxadiol saponins to metabolites I-III in the intestines seems most partly due to intestinal P.oris. In addition, the fact that neither intact ginsenoside Rb1 nor its middle metabolic derivatives but only the final metabolite I was detected at 1.0-7.3 micrograms/ml in blood after oral administration of mice with ginsenoside Rb1 (125 mg/kg) allows us to speculate that metabolites I-III are the most likely forms of protopanaxadiol saponins absorbed from the intestines.