Toshio Fukai

Anti-Helicobacter pylori flavonoids from licorice extract.

Licorice is the most used crude drug in Kampo medicines (traditional Chinese medicines modified in Japan). The extract of the medicinal plant is also used as the basis of anti-ulcer medicines for treatment of peptic ulcer. Among the chemical constituents of the plant, glabridin and glabrene (components of Glycyrrhiza glabra), licochalcone A (G. inflata), licoricidin and licoisoflavone B (G. uralensis) exhibited inhibitory activity against the growth of Helicobacter pylori in vitro. These flavonoids also showed anti-H. pylori activity against a clarithromycin (CLAR) and amoxicillin (AMOX)-resistant strain. We also investigated the methanol extract of G. uralensis. From the extract, three new isoflavonoids (3-arylcoumarin, pterocarpan, and isoflavan) with a pyran ring, gancaonols A[bond]C, were isolated together with 15 known flavonoids. Among these compounds, vestitol, licoricone, 1-methoxyphaseollidin and gancaonol C exhibited anti-H. pylori activity against the CLAR and AMOX-resistant strain as well as four CLAR (AMOX)-sensitive strains. Glycyrin, formononetin, isolicoflavonol, glyasperin D, 6,8-diprenylorobol, gancaonin I, dihydrolicoisoflavone A, and gancaonol B possessed weaker anti-H. pylori activity. These compounds may be useful chemopreventive agents for peptic ulcer or gastric cancer in H. pylori-infected individuals.

Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus.

Nineteen flavonoids isolated from licorice (Glycyrrhiza glabra, G. inflata and G. uralensis) were tested for their antimicrobial activities against methicillin sensitive Staphylococcus aureus, methicillin resistant S. aureus, Micrococcus luteus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Chemistry of phenolic compounds of licorice (Glycyrrhiza species) and their estrogenic and cytotoxic activities

The genus Glycyrrhiza consists of about 30 species in which G. glabra, G. uralensis, G. inflata, G. aspera, G. korshinskyi, and G. eurycarpa are generally recognized as licorice because of their sweet taste. Except G. korshinskyi, we examined isoprenoid-substituted phenols of these licorices. Each plant could be characterized by some isoprenoid phenols. We also investigated the biological activities of the Glycyrrhiza phenols. In the course of screening phytoestrogen in medicinal plants, six Glycyrrhiza phenols exhibited the binding affinities for the bovine uterine estrogen receptor. The affinity of a dihydrostilbene with two 3-methyl-2-butenyl (prenyl) groups, gancaonin R, was higher than those of isoflavone phytoestrogens (genistein and daidzein) in dietary foods. The affinities of the other five phenols, a flavanone (liquiritigenin), two prenylflavanones (isobavachin and sigmoidin B), a prenylated coumestan (glycyrol), and a pyranoisoflav-3-ene (glabrene), were similar to that of the dietary isoflavone, genistein or daidzein. Cytotoxic activities of the Glycyrrhiza phenols against human oral tumor cell lines and HIV-infected MT-4 cells were also reviewed.

Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza glabra.

Antinephritis activity of glabridin, a pyranoisoflavan isolated from Glycyrrhiza glabra, was evaluated after its oral administration to mice with glomerular disease (Masugi-nephritis) by measuring the urinary protein excretion, total cholesterol, serum creatinine and blood urea nitrogen levels. Administration of glabridin for 10 days (30 mg kg(-1) day(-1)) reduced the amount of urinary protein excretion from control level (100+/-23 mg/day) to a significantly lower level (47+/-4 mg/day). ESR spectroscopy demonstrated that glabridin neither produced radical, nor affected the radical intensity of sodium ascorbate, suggesting the lack of correlation between the antinephritis activity and radical scavenging activity.

Seven prenylated flavonol glycosides from two Epimedium species

Abstract Five new flavonol glycosides, ikarisosides B, C, D, E and F were isolated from the roots of Epimedium grandiflorum and their structures elucidated as 8-prenylkaempferol-3- O -β-glucosyl (1→2)-α-rhamnoside, 8-prenylkaempferol 3- O -β-glucosyl(1→2)-α-rhamnoside]-7- O -β-glucoside, 8-prenylkaempferol 3- O -α-(4″ acetyl rhamnoside, 6″,6″-dimethylpyrano(2″,3″: 7,8) kaempferol 3- O -α-rhamnoside and 8-prenylkaempferol 3- O -β-xylosyl(1→2)-α-rhamnoside, respectively. Ikarisoside A was also isolated from the same material and confirmed as the hydrolysis product of epimedoside A. From the root E. sempervirens , ikarisosides A, C and E, as well as icarisid II were isolated. Ikarisoside A and icarisid II were isolated for the first time as natural products.

Involvement of reactive oxygen species in sonodynamically induced apoptosis using a novel porphyrin derivative.

In this study, we investigated the induction of apoptosis by ultrasound in the presence of the novel porphyrin derivative DCPH-P-Na(I). HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of DCPH-P-Na(I), and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity. Reactive oxygen species were measured by means of ESR and spin trapping technique. Cells treated with 8 μM DCPH-P-Na(I) and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound or DCPH-P-Na(I) alone. Also, DNA ladder formation and caspase-3 activation were observed in cells treated with both ultrasound and DCPH-P-Na(I) but not in cells treated with ultrasound or DCPH-P-Na(I) alone. In addition, the combination of DCPH-P-Na(I) and the same acoustical arrangement of ultrasound substantially enhanced nitroxide generation by the cells. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. These results indicate that the combination of ultrasound and DCPH-P-Na(I) induced apoptosis in HL-60 cells. The significant reduction in sonodynamically induced apoptosis, nitroxide generation, and caspase-3 activation by histidine suggests active species such as singlet oxygen are important in the sonodynamic induction of apoptosis. These experimental results support the possibility of sonodynamic treatment for cancer using the induction of apoptosis.

Isoprenylated flavonoids from underground parts of Glycyrrhiza glabra

Two new pyrano-2-arylbenzofurans, kanzonols U and V, a pyrano-3-arylcoumarin, kanzonol W, a diprenylated isoflavan, kanzonol X, a diprenylated α-hydroxydihydrochalcone, kanzonol Y, were isolated from the underground parts of cultivated Glycyrrhiza glabra. Their structures were elucidated by spectroscopic methods. The structure of glabrene was revised.

Constituents of the cultivated mulberry tree.

From extracts of root bark of the cultivated mulberry tree (a variety of Morus alba L.) three new isoprene-substituted flavanones, Kuwanon D, E and F were isolated. Their structures were shown to be I, II and III, respectively.

An isoprenylated flavanone from Glycyrrhiza glabra and rec-assay of licorice phenols

Abstract A new prenylated 3-hydroxypyranoflavanone, kanzonol Z, was isolated from cultivated licorice, Glycyrrhiza glabra , and the structure elucidated from spectral evidence. The stereochemical structure of kanzonol Y previously isolated from the licorice has been shown to be ( α R )-3,5′-diprenyl- α ,2′,4,4′-tetrahydroxydihydrochalcone by Moshers method. In a prescreening test for bioactive compounds amongst licorice phenols using a recombinationless mutant of Bacillus subtilis M45, seven compounds showed induction activities of DNA damage.

Five isoprenoid-substituted flavonoids from Glycyrrhiza eurycarpa

Abstract A new prenylated dibenzoylmethane, kanzonol A, and a new chalcone, kanzonol B, along with two new isoprenoid-substituted flavones, kanzonols D and E were isolated from the roots of Glycyrrhiza eurycarpa. Their structures were elucidated by spectroscopic methods. The diprenylated chalcone, kanzonol C, was also isolated from this species for the first time as a natural product.