Masaki Baba

Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development

Isoliquiritigenin (ILTG), a flavonoid group compound, exists in some foodstuffs and herbal medicines such as licorice (Glycyrrhiza uralensis Fisher). Previously, we showed that ILTG can suppress azoxymethane (AOM)‐induced colon carcinogenesis in ddY mice. In the present report, we present evidence that ILTG markedly decreases both prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW264.7 mouse macrophage cells. The decrease of PGE2 was dependent on cyclooxygenase‐2 (COX‐2) expression and the decrease of NO appeared due to a decrease in inducible nitric oxide synthase (iNOS) protein expression. In mouse and human colon carcinoma cells, ILTG treatment suppressed cell growth and caused apoptosis. Furthermore, in vivo administration of ILTG inhibited the induction of preneoplastic aberrant crypt foci (ACF) in the male F344 rat colon. Our results suggest that ILTG is a promising chemopreventive agent against colon carcinogenesis.

Isoliquiritigenin inhibits the growth of prostate cancer.

OBJECTIVE Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. In this study, we investigated the anti-tumor effect of isoliquiritigenin on prostate cancer in vitro. METHODS DU145 and LNCaP prostate cancer cell lines were used as targets. We examined the effects of isoliquiritigenin on cell proliferation, cell cycle regulation and cell cycle-regulating gene expression. Further, we investigated the effects of isoliquiritigenin on the GADD153 mRNA and protein expression, and promoter activity. RESULTS Isoliquiritigenin significantly inhibited the proliferation of prostate cancer cell lines in a dose-dependent and time-dependent manner. Fluorescence-activated cell sorting (FACS) analysis indicated that isoliquiritigenin induced S and G2/M phase arrest. Isoliquiritigenin enhanced the expression of GADD153 mRNA and protein associated with cell cycle arrest. Further, isoliquiritigenin stimulated transcriptional activity of GADD153 promoter dose-dependently. CONCLUSION These findings suggest that isoliquiritigenin is a candidate agent for the treatment of prostate cancer and GADD153 may play an important role in isoliquiritigenin-induced cell cycle arrest and cell growth inhibition.

Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma

Isoliquiritigenin is a chalcone isolated from licorice and shallots. The ability of isoliquiritigenin to suppress metastasis was examined in a pulmonary metastasis model of mouse renal cell carcinoma. Isoliquiritigenin significantly reduced pulmonary metastasis, without any weight loss or leukocytopenia. Isoliquiritigenin suppressed in vitro proliferation of carcinoma cells, potentiated nitric oxide production by lipopolysaccharide-stimulated macrophages, and facilitated cytotoxicity of splenic lymphocytes in vitro. These findings suggest activation of macrophages, activation of cytotoxicity of lymphocytes, and direct cytotoxicity as possible mechanisms of metastasis suppression by isoliquiritigenin. In addition, isoliquiritigenin prevented severe leukocytopenia caused by administration of 5-fluorouracil.

Antidiabetic effect of polyphenols from brown alga Ecklonia kurome in genetically diabetic KK-Ay mice

Context: Prevalence of diabetes mellitus type 2 (DM-II) is increasing in Japan. Brown alga Ecklonia kurome Okamura (Laminariaceae) (kurome in Japanese) is rich in phlorotannins, a kind of polyphenol. Phlorotannins have been reported to possess various bioactivities; however, few studies have reported its effect on DM-II. Objective: The present study was conducted to investigate the antidiabetic effect of polyphenols from E. kurome (KPP) on KK-Ay mice, the animal model for human DM-II. Materials and methods: Inhibitory activities of KPP against α-amylase and α-glucosidase in vitro, and effects on oral carbohydrate tolerance test in vivo were investigated. KK-Ay mice were fed with 0.1% KPP containing water for 5 weeks. A glucose tolerance test was conducted at week 4 of the 5-week period. At the end of experiment, blood biochemical parameters, including blood glucose, insulin, glycoalbumin, and fructosamine were determined. Furthermore, the kidneys and pancreatic islets were histologically examined. Results: KPP showed inhibitory activities on carbohydrate-hydrolyzing enzymes and decreased postprandial blood glucose levels. The body weight gain and blood glucose levels in the KPP group were lower than the control group during the experimental period. KPP improved glucose tolerance and decreased the fasting blood glucose and insulin levels, fructosamine and glycoalbumin levels compared with the control group. Furthermore, KPP contracted the pancreatic islet size and decreased renal mesangial matrix in KK-Ay mice. Discussion and conclusion: These results suggest that KPP is effective against DM-II and might provide a source of therapeutic agents for DM-II.

Coumarins Isolated from the Roots of Seseli resinosum. in Turkey

Abstract Seseli resinosum. Freyn et Sint. (Umbelliferae) is a perennial herb that grows in the northern region of Anatolia, Turkey. The n.-hexane extract obtained from the roots of S. resinosum. was investigated for the presence of coumarins. Three angular-type pyranocoumarins and two linear-type furocoumarins were isolated from the roots. The compounds were identified as (+)-samidin [(3′S., 4′S.)-3′-senecioyloxy-4′-acetoxy-3′, 4′-dihydroseselin] (1), (−)-anomalin [(3′R., 4′R.)-3′, 4′-diangeloyloxy-3′, 4′-dihydroseselin] (2), calipteryxin (3′R., 4′R.)-3′-angeloyloxy-4′-senecioyloxy-3′, 4′-dihydroseselin (3), isoimperatorin (4), and deltoin (5). The structures were determined using spectroscopic methods (1H NMR, 13C NMR, 1H-1H COSY, 1H-13C COSY, HMBC, MS), physical methods (melting point and optical rotation), and chemical correlations with known compounds that have been described in the literature. The chemotaxonomic significance of these isolated coumarins is discussed in the genus Seseli. L.

HPLC analysis of coumarins in Turkish Seseli species (Umbelliferae)

The n-hexane extracts of aerial and underground parts of three Seseli species, S. gummiferum subsp. corymbosum, S. resinosum, and S. hartvigii growing in Turkey were investigated concerning the presence of coumarins by normal-phase HPLC (high-performance liquid chromatography). In this respect, two coumarins, osthol (1) and corymbocoumarin (2) [(−)-(3′S, 4′S)-3′-acetoxy-4′-isovaleryloxy-3′, 4′-dihydroseselin] isolated from aerial parts of S. gummiferum subsp. corymbosum, were used as standard samples. The amount of these compounds were discussed and evaluated in this study.

The constituents of Urtica cannabina used in Uighur medicine.

Urtica cannabina L. (Urticaceae) is a perennial herb that grows in Xinjiang Uighur Autonomous Region (northwest China). Two megastigmanes (1, 2) and five flavonoid glycosides (3-7) were isolated from its fruit. Compound 1 was determined by spectroscopic analysis to be (+)-blumenol A, and its absolute stereochemistry was determined in detail using chemical conversion and a modification of Mosher’s method. Other compounds were identified as (+)-dehydrovomifoliol (2), isovitexin (3), isoquercitrin (4), astragalin (5), afzelin (6), and quercitrin (7) using spectroscopic (NMR, HMBC, MS) and physical methods (melting point and optical rotation). Compounds 1-7 were isolated from this plant for the first time, while this is the first report of megastigmanes in the Urticaceae family. The chemotaxonomic significance of the isolation of these megastigmanes and flavonoid glycosides from Urtica species is discussed.

New triterpenoid saponins from cacti and anti-type I allergy activity of saponins from cactus.

The research in our laboratory focuses on the isolation of saponins from cactus. In this study, we report five new triterpenoid saponins, dumortierinoside A methyl ester (1), pachanoside I1 (2), pachanoside D1 (3), gummososide A (4), and gummososide A methyl ester (5). Compounds 1-3 isolated from Isolatocereus dumortieri Backbg., and compounds 4 and 5 were isolated from Stenocereus alamosensis A. C. Gibson & K. E. Horak. Compound 2 possessed a new pachanane-type triterpene skeleton, pachanol I, in its aglycon. The aglycon of 3 was pachanol D, while those of 4 and 5 were both gummosogenin, which we have previously reported, but this is the first report of pachanol D and gummosogenin in their aglycon forms. Additionally, we evaluated the anti-type I allergy activity of the saponins with RBL-2H3 (Rat basophilic leukemia) cells by measuring the β-hexosaminidase release inhibitory activity. As a result of these studies, gummososide A methyl ester (5) was found to show activity (IC(50)=99.5 μM) and thurberoside A exhibited mild activity (IC(50)=166.9 μM).