Shoko Taniguchi

Production of bioactive triterpenes by Eriobotrya japonica calli

Callus tissue cultures induced from an axenic leaf of Eriobotrya japonica (Rosaceae) produced triterpenes in large amounts (ca. 50 mg/g dry wt). Nine triterpenes were characterized as ursolic acid, oleanolic acid, 2alpha-hydoxyursolic acid, maslinic acid, tormentic acid, 2alpha, 19alpha-dihydroxy-3-oxo-urs-12-en-28-oic acid, hyptadienic acid and a mixture of 3-O-cis-p-coumaroyltormentic acid and 3-O-trans-p-coumaroyltormentic acid. The triterpene composition in the callus tissues was noticeably different from that in intact leaves. The contents of tormentic acid with antidiabetic action, and 2alpha, 19alpha-dihydroxy-3-oxo-urs-12-en-28-oic acid with anti-HIV activity, were much larger than those in the intact leaves. All of the triterpenes isolated from the callus tissues showed an inhibitory effect comparable to (-)-epigallocatechin gallate (EGCG) of green tea on the activation of Epstein-Barr virus early antigen (EBV-EA) induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 2alpha, 19alpha-Dihydroxy-3-oxo-urs-12-en-28-oic acid was the most potent inhibitor among them and caused a significant delay of two-stage carcinogenesis on mouse skin.

New TNF-α releasing inhibitors as cancer preventive agents from traditional herbal medicine and combination cancer prevention study with EGCG and sulindac or tamoxifen

Herbal medicines are now attracting attention as potential sources of cancer preventive agents. Using inhibition of tumor necrosis factor-alpha (TNF-alpha) release assay, we studied Acer nikoense, Megusurino-ki in Japanese. Inhibitory potential was found in the leaf extract, and the main active principles were identified as geraniin and corilagin. The IC(50) values for TNF-alpha release inhibition were 43 microM for geraniin and 76 microM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG), the green tea polyphenol, as control was 26 microM. Furthermore, treatment with geraniin inhibited okadaic acid tumor promotion in a two-stage carcinogenesis experiment on mouse skin. Geraniin and corilagin are present in another well-known Japanese traditional herb, Geranium thunbergii, Genno-shoko in Japanese. Considering seasonal variations of the agents and sites of cultivation of herbs, this paper reviews the significance of geraniin as a new cancer preventive agent. In addition, based on accumulated results of green tea as a cancer preventive, we review two important results with EGCG: the synergistic effects of EGCG with sulindac or tamoxifen on cancer preventive activity in PC-9 cells, and cancer prevention of intestinal tumor development in multiple intestinal neoplasia (Min) mice by cotreatment using EGCG with sulindac. We report here new findings on additional gene expression resulting from cotreatment with EGCG and sulindac in PC-9 cells compared with gene expression by EGCG alone or sulindac alone. Overall, our results indicate that, with the continuing spread of cancer chemoprevention as a fundamental medical strategy, both clinicians and researchers should take a closer look at herbal medicine.

Hydrolyzable tannins of tamaricaceous plants. III.1 Hellinoyl-and macrocyclic-type ellagitannins from Tamarix nilotica

Three new hellinoyl-type ellagitannins, nilotinins M4 (7), D7 (8), and D8 (9), and a new macrocyclic-type, nilotinin D9 (10), together with eight known tannins, hirtellins B (2), C (11), and F (12), isohirtellin C (13), tamarixinin A (3), tellimagrandins I and II, and 1,2,6-tri-O-galloyl-beta-d-glucose (14), were isolated from an aqueous acetone extract of Tamarix nilotica dried leaves. Nilotinin M4 (7) is a monomeric tannin possessing a hellinoyl moiety. The structure of 8 demonstrated replacement of one of the HHDP groups at the glucose core O-4/O-6 in ordinary dimeric tannins with a galloyl moiety at O-6. This is a new structural feature among the tamaricaceous ellagitannins. On the basis of the results, reported spectroscopic assignments for 2, 3, and the macrocyclic tannins 11-13 were revised. Unusual shifts in the NMR spectra of these macrocyclic tannins are also discussed in relation to their conformations. Several tannins isolated from T. nilotica were assessed for possible cytotoxic activity against four human tumor cell lines, and nilotinin D8 (9) and hirtellin A (1) showed high cytotoxic effects.

Galloylglucoses and riccionidin A in Rhus javanica adventitious root cultures.

Adventitious root cultures of Rhus javanica L. produced large amounts of galloylglucoses (gallotannins) and an anthocyanidin, riccionidin A, formerly found only in liverworts. Production of both galloylglucoses and riccionidin A in the adventitious root culture system was suppressed by light. The Rhus root culture showed the highest productivity for those secondary metabolites in a modified Linsmaier-Skoog (LS) liquid medium containing 30 mM NH4+ and 30 mM NO3- as nitrogen sources in the presence of 10(-6) M 3-indoleacetic acid (IAA).

Modified limonoids from the leaves of Sandoricum koetjape

Three trijugin-type limonoids, sandrapins A, B and C, were isolated from the leaves of Sandoricum koetjape and their structures, which are related to capensolactones, were elucidated by a detailed 2D-NMR spectroscopic analysis.

Production of macrocyclic ellagitannin oligomers by oenothera laciniata callus cultures

Callus cultures of Oenothera laciniata grown on LS agar medium supplemented with IAA and kinetin produced large amounts of the macrocyclic ellagitannin dimer, oenothein B, and a trimer, oenothein A, accompanied with related monomeric hydrolysable tannins. The content of the main compound oenothein B (65 mg/g dry wt) in calli cultured on modified LS medium containing 10 mM NH4+ and 5 mM NO3- was nearly two times higher than that in intact leaves.

A macrocyclic ellagitannin trimer, oenotherin T1, from Oenothera species

Oenotherin T(1) was isolated from leaves of Oenothera tetraptera as a major ellagitannin. Its structure, that of a macrocyclic trimer with a new acyl group, an isodehydrovaloneoyl group, was established. This compound was also produced by callus tissues induced from O. laciniata leaves.

Monomeric and dimeric hydrolysable tannins of Tamarix nilotica

An ellagitannin monomer, nilotinin M1 (1), and three dimers, nilotinins D1 (2), D2 (3), and D3 (4), were isolated from leaves of Tamarix nilotica (Ehrenb.) Bunge. Structures were elucidated based on analysis of spectroscopic data and chemical correlations with known compounds. In addition, six known tannins, hirtellin A (5) (dimer), remurin A (6), remurin B (7), 1,3-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-beta-D-glucose (8), gemin D (9), and hippomanin A (10) (monomers), were isolated for the first time from this plant species. The reported (13)C NMR assignments of the dehydrodigalloyl moiety and glucose cores of 5 are revised, and the (13)C NMR spectroscopic data for 6 and 7 are also reported for the first time.

Hydrolyzable Tannins of Tamaricaceous Plants. V. Structures of Monomeric–Trimeric Tannins and Cytotoxicity of Macrocyclic-Type Tannins Isolated from Tamarix nilotica(1)

Three new ellagitannin monomers, nilotinins M5-M7 (1-3), a dimer, nilotinin D10 (4), and a trimer, nilotinin T1 (5), together with three known dimers, hirtellin D (7) and tamarixinins B (8) and C (9), and a trimer, hirtellin T2 (6), were isolated from Tamarix nilotica dried leaves. The structures of the tannins were elucidated by intensive spectroscopic methods and chemical conversions into known tannins. The new trimer (5) is a unique macrocyclic type whose monomeric units are linked together by an isodehydrodigalloyl and two dehydrodigalloyl moieties. Additionally, dimeric and trimeric macrocyclic-type tannins isolated from T. nilotica in this study were assessed for possible cytotoxic activity against four human tumor cell lines. Tumor-selective cytotoxicities of the tested compounds were higher than those of synthetic and natural potent cytotoxic compounds, including polyphenols, and comparable with those of 5-fluorouracil and melphalan.

Constituents of Psoralea corylifolia Fruits and Their Effects on Methicillin-Resistant Staphylococcus aureus

Two new flavonoids, bakuisoflavone (1) and bakuflavanone (2), together with 15 known compounds, were isolated from the fruits of Psoralea corylifolia, and their structures were characterized by spectroscopic data. The effects of the isolated compounds on methicillin-resistant Staphylococcus aureus were also examined. We found that two compounds, isobavachalcone (10) and bakuchiol (12), showed noticeable antibacterial effects on the MRSA strains examined. Quantitation of the major constituents, including anti-MRSA constituents, was then performed. The results showed individual contents of 1.26%–16.49% (w/w) among the examined compounds in the ethyl acetate extract from P. corylifolia fruits.