Phenolics from Glycyrrhiza glabra and G. uralensis Roots and Their PPAR-γ Ligand-Binding Activity: Possible Application for Amelioration of Type 2 Diabetes

The EtOH extract of Glycyrrhiza glabra roots and the EtOAc extract of Glycyrrhiza uralensis roots exhibited considerable PPAR-γ ligand-binding activity. Bioassay-guided fractionation of these extracts resulted in the isolation of 52 phenolics, including 11 novel ones. The PPAR-γ ligand-binding activity of more than 10 isolated phenolics at 10 μg/mL was approximately three times greater than that of 0.5 μM triglitazone. Glycyrin (44), isolated from the EtOAc extract of G. uralensis roots as a PPAR-γ ligand, reduced the blood glucose levels of genetically diabetic KK-Ay mice through its PPAR-γ ligand-binding activity

Characterization of the growth-inhibitory and apoptosis-inducing activities of a triterpene saponin, securioside B against BAC1.2F5 macrophages.

BACKGROUND: Since the growth state of macrophages in local pathological sites is considered a factor that regulates the processes of many disease, such as tumors, inflammation, and atherosclerosis, the substances that regulate macrophage growth or survival may be useful for disease control. We previously reported that securiosides A and B, novel triterpene saponins, exerted macrophage-oriented cytotoxicity in the presence of a L-cell-conditioned medium containing macrophage colony-stimulating factor (M-CSF), while the compounds did not exhibit an effect on macrophages in the absence of the growth-stimulating factors. AIM: This study was undertaken to characterize the growth-inhibitory and the apoptosis-inducing activities of securioside B, focusing on the effects of the macrophage-growth factor(s), and to examine the implication of a mitochondria pathway in apoptosis induction. METHODS: The effect of securioside B on a murine macrophage cell line (BAC1.2F5) was examined by MTT assay and lactose dehydrogenase release assay in the presence of L-cell-conditioned medium, M-CSF, or granulocyte-macrophage CSF (GM-CSF). RESULT: Securioside B inhibited the growth of the cells stimulated by recombinant M-CSF or GM-CSF, but it scarcely induced cytolysis of the cells under the same conditions. Moreover, securioside B did not induce cell death when the compound only was added to the cells. On the other hand, the compound extensively induced apoptotic cell death in the presence of L-cell-conditioned medium, suggesting that apoptosis induction by securioside B requires the additional factor(s) present in L-cell-conditioned medium. Securioside B plus L-cell-conditioned medium induced the activation of caspase-3 and caspase-9, but not caspase-8. In addition, cytochrome c release from the mitochondria into the cytosol, and disrupted mitochondria membrane potential, was also observed in the apoptotic BAC1.2F5 cells. CONCLUSION: These data suggest that securioside B has growth-inhibitory activity against growth factor-stimulated macrophages, and that it induces apoptotic macrophage death through the activation of a mitochondrial pathway in the presence of L-cell-conditioned medium

Effects of the spring water on the dissolution of aminophylline tablet and theophylline sustained-release preparations

薬物のbioavailabilityに影響する因子の一つとして,製剤からの薬物の溶出速度が考えられる｡今回,温泉水による薬物溶出への影響を知る目的で,気管支喘息治療薬のアミノフィリン製剤およびテオフィリン徐放製剤の溶出挙動について検討した｡溶出試験は第12改正日本薬局方に従い,第1法(回転バスケット法)および第2法(パドル法)で行い,試験液を蒸留水および三朝温泉水として両者の溶出挙動を比較した｡アミノフィリン製剤では,10分後まで 温泉水の方が有意に高い溶出率を示した｡また,テオフィリン徐放製剤においても温泉水が8時間後まで蒸留水に比べて有意に高い溶出率を示した｡以上の結果より,アミノフィリン製剤およびテオフィリン徐放製剤は温泉水により薬物の溶出が促進されることか示唆された。The dissolutions of aminophylline tablet and theophylline sustained-release preparattions in Misasa spring water were examined using the rotating basket and paddle methods. The dissolution rate of aminophylline tablet with the spring water was higher than that with distilled water from starting to 10 min after the test. In theophylline sustained-release preparations, the spring water showed a facilitation on the dissolution rate in comparison to the distilled water for 8 hours after the test. These results indicate that the spring water enhanced the releasing rates of aminophylline tablet and theophylline sustained-release preparations