Akira Inada

Antimicrobial alkaloids from Zanthoxylum tetraspermum and caudatum.

Two benzophenanthrene alkaloids, 8-acetonyldihydronitidine and 8-acetonyldihydroavicine were isolated from Zanthoxylum tetraspermum stem bark along with liriodenine, sesamin, lichexanthone and (+)-piperitol-gamma,gamma-dimethylallylether. The species endemic to Sri Lanka, Z. caudatum, contained sesamin, savinin, liriodenine, decarine and 8-O-desmethyl-N-nornitidine. 8-Acetonyldihydronitidine and 8-acetonyldihydroavicine showed significant antibacterial activity while the former along with liriodenine was strongly antifungal. Savinin exhibited potent spermicidal activity. Both savinin and sesamin exhibited significant insecticidal activity.

Flavonoid glycosides of the roots of Glycyrrhiza uralensis

Abstract The structure of a flavanone glycoside from the roots of Glycyrrhiza uralensis has been confirmed as 4′-O-[β- d -apio- d -furanosyl-(1 → 2)-β- d -glucopyranosyl]liquiritigenin. In addition, two known flavonoid glucosides, ononin (a minor component) and liquiritin (a major component), were isolated from the same extract.

Potentiation of Nerve Growth Factor-Induced Neurite Outgrowth in PC12 Cells by a Coptidis Rhizoma Extract and Protoberberine Alkaloids

A methanol extract of Coptidis Rhizoma effectively enhanced the outgrowth of neurite in PC12 cells induced by nerve growth factor (NGF). Following solvent partition and preparative HPLC, berberine was isolated as the major active compound. Berberine enhanced the proportion of neurite-bearing cells in a dose-dependent manner without cytotoxicity. Its structural relatives, palmatine and coptisine, showed a slightly weaker NGF-enhancing effect than berberine. These three alkaloids inhibited acetylcholinesterase activity at a level comparable to that of physostigmine, but this inhibition was not responsible for the potentiation of NGF-induced neurite outgrowth. It is demonstrated for the first time that protoberberine alkaloids potentiated the NGF-induced differentiation of neural cells.

Isolation of apoptosis- and differentiation-inducing substances toward human promyelocytic leukemia HL-60 cells from leaves of Juniperus taxifolia.

A chloroform extract of the leaves of Juniperas taxifolia exhibited a marked antiproliferative effect on human promyelocytic leukemia HL-60 cells at a concentration of 2.5 μg/ml. Deoxypodophyllotoxin (4) was identified in the extract as an outstanding antiproliferative compound, and five diterpenes (1–3, 5, and 6) were isolated as known compounds with weak or no cytotoxicity. These compounds were examined for their respective apoptosis- and differentiation-inducing activities toward HL-60 cells by DNA fragmentation and NBT-reducing assays, respectively. Among them, 7α-hydroxysandaracopimaric acid (6) was found to have a potent differentiation-inducing activity in a dose-dependent manner at 0.125–2 μg/ml (0.39–6.29 μM), together with apoptosis-inducing activity at concentrations of more than 2.5 μg/ml (7.86 μM). Deoxypodophyllotoxin (4) that exerted cytotoxic and apoptosis-inducing activities at 2 ng/ml (5 nM) did not induce differentiation at the same concentration, and the other diterpenes (1–3 and 5) showed no effect on cell differentiation, even at 5 μg/ml. It was thus demonstrated for the first time that 7α-hydroxysandaracopimaric acid was an effective differentiation-inducing compound toward HL-60 cells.

Induction of apoptosis by hinokitiol, a potent iron chelator, in teratocarcinoma F9 cells is mediated through the activation of caspase‐3

Abstract. Hinokitiol, a potent iron chelator, has been reported to induce differentiation in teratocarcinoma F9 cells with a reduction of viable cells. In this study, we examined the steps leading to eventual cell death by hinokitiol during differentiation. Hinokitiol induced DNA fragmentation of F9 cells in a concentration‐and time‐dependent manner. This effect was also observed in a cell‐free system using the nuclei from intact cells and the cytosols from hinokitiol‐treated cells. In contrast, hinokitiol methyl ether and hinokitiol‐‐Fe (III) complex, which are deficient in iron‐chelating activity, showed no DNA fragmentation activity in both cell culture and cell‐free systems. These results suggest that iron deprivation by hinokitiol may be involved in the induction of apoptosis of F9 cells. Caspase‐3, one of the key enzymes in the apoptotic cascade, was specifically activated by hinokitiol treatment, but not by the other two derivatives. In addition, its specific inhibitor, benzyloxycarbonyl‐Val‐Ala‐Asp‐fluoromethyl ketone, strongly blocked hinokitiol‐induced DNA fragmentation. These results indicate that iron deprivation by hinokitiol can induce apoptosis of F9 cells through the activation of caspase‐3.

Induction of differentiation and apoptosis by dithizone in human myeloid leukemia cell lines

We investigated the effect of diphenylthiocarbazone (dithizone) and its structurally related compounds on the differentiation and apoptosis of two human myeloid leukemia cell lines. Dithizone caused a time- and concentration-dependent induction of differentiation in both the promyelocytic leukemia cell line HL-60 cells and the myeloblastic leukemia cell line ML-1 cells, as measured by nitroblue tetrazolium (NBT) reducing activity. Morphological changes and esterase activities confirmed that this differentiation took place. The induction of differentiation required the addition of dithizone to the culture medium for at least 12 h. The differentiation inducing activity was inhibited by the preincubation of dithizone with various metal ions such as Pb2+, Zn2+, Cu2+ and Mn2+ ions, but not with Fe3+ and Mg2+ ions. In addition, the DNA extracted from dithizone-treated HL-60 cells showed a typical ladder pattern characteristic of apoptosis in agarose gel electrophoresis. A quantitative analysis of DNA fragmentation revealed that this apoptosis was concentration- and time-dependent in both the HL-60 and ML-1 cells. Dithizone-induced apoptosis was also inhibited by preincubation with Mn2+ ions, but not with Mg2+ ions. These results indicate that dithizone induces both differentiation and apoptosis in HL-60 and ML-1 cells through a unique mechanism including metal chelation.

Cycloartane triterpenoids from Aglaia harmsiana

Abstract Two new and two known cycloartane-type triterpenoids were isolated from the leaves of Aglaia harmsiana. The structures were determined using 1H, 13C and 2D NMR techniques.

Pregnanes and triterpenoid hydroperoxides from the leaves of Aglaia grandis

Abstract Three pregnanes and two known cycloartane-type triterpenoid hydroperoxides were isolated from the leaves of Aglaia grandis . Their structures were determined using 1 H, 13 C and 2D NMR techniques.

Conversion of 2′-hydroxychalcones to flavanones catalyzed by cobalt Schiff base complex

Abstract Co(salpr) catalyzes the conversion of 2′-hydroxychalcones to flavanones in methanol under oxygen. Base catalysis by Co(salpr) (OH) produced in situ is responsible for the reaction, which is found to proceed reversibly.

New Neolignan and Phenylpropanoid Glycosides in Juniperus communis var. depressa

Two new neolignan glucosides (junipercomnosides C and D) and two new phenypropanoid glycosides (junipercomnosides E and F) were isolated from aerial parts of Juniperus communis var. depressa along with seven known phenylpropanoid glycosides. The structures of the isolated compounds were determined by spectral analysis, in particular by the detailed analysis of 2D NMR and CD spectra.