Amino Acid Conjugates of ent-Beyerane-type Diterpenoids and Oleanane-type Triterpenoids: Synthesis and Evaluation of Cytotoxic Activities.

The aim of this study was to increase the cytotoxic activities of terpenoids via amino acid conjugation. Thus, 21 new ester derivatives (5-15, 19-27, and 29) were prepared by conjugation of the hydroxy groups in ent-beyerane-type diterpenoids (4) and oleanane-type triterpenoids (18), and their cytotoxic activity against three human cancer cell lines (leukemia, lung, and stomach) were evaluated. The prepared compounds showed cytotoxic effects; in particular, all amino acid conjugates of ent-beyerane-type diterpenoids (5-13) exhibited potent cytotoxic activity (IC50 1.0-3.7 µM for HL60, 1.7-8.2 µM for A549, and 2.5-11.7 µM for MKN45). In addition, no differences were observed in the cytotoxic activities of l- and d-type amino acid conjugates.

[Subjective Contrast of Pulmonary Tissues in CsI-FPD Chest Radiography Using Model Phantom by Monte Carlo Simulation].

OBJECTIVE: Subject contrast of pulmonary tissues was investigated for five X-ray beams (70 kV without filter, 90 kV with 0.15 mm Cu filter, 90 kV with 0.2 mm Cu filter, 120 kV without filter, and 120 kV with 0.2 mm Cu filter) in CsI-FPD chest radiography using two types of model phantoms by Monte Carlo simulation. METHODS: A total of 72 million photons were entered to the model lung phantom (width, 300 mm; length, 300 mm; thickness, 200 mm; air space, 120 mm) and model mediastinum phantom (width, 300 mm; length, 300 mm; thickness, 200 mm; air space, 40 mm). Individual primary and secondary photon's process (absorption, scattering, and penetration) in the phantom and CsI-detector was recorded by Monte Carlo simulation. Subject contrast was calculated by entered and absorbed photon's number in the CsI-detector. RESULTS: Subject contrast pulmonary tissues were high to low energy X-ray beam; however, the ones of soft tissue and soft tissue overlaying bone had few differences for beam quality except 70 kV without filter. Moreover, the subject contrast by absorbed photons was higher compared to the one by entered photons in CsI. CONCLUSION: It was shown that the subject contrast study by Monte Carlo calculation can be replaced by the way of physical chest phantom, and that the subject contrast by absorbed photons and by injected photons in CsI was different. Furthermore, be verified that the subject contrast of soft tissue and soft tissue overlaying bone differs hardly.

Solvent-Free Synthesis of 2-Alkylbenzothiazoles and Bile Acid Derivatives Containing Benzothiazole Ring by Using Active Carbon/Silica Gel and Microwave.

A highly efficient and simple method for the synthesis of 2-alkylbenzothiazoles through the condensation of 2-aminothiophenol and aliphatic aldehydes in the presence of active carbon/silica gel is described. The reaction proceeded under solvent-free and microwave irradiation to afford 2-alkylbenzothiazoles in high yields. This method was extended to the synthesis of bile acid derivatives containing a benzothiazole ring and obtained the desired products in high yields. The anti-inflammatory activity and cytotoxicity of the newly synthesized benzothiazole derivatives of bile acid were tested; the results showed that anti-inflammatory activities of all tested compounds tested were higher than that of standard drugs, such as indomethacin.

Synthesis of Lanostane-Type Triterpenoid N-Glycosides and Their Cytotoxicity against Human Cancer Cell Lines.

Seventeen lanostane-type triterpenoid derivatives (2 - 18), including 11N-glycosides (8 - 18), were synthesized from the natural triterpenoid, lanosterol (1), and were evaluated for their cytotoxicity against the human cancer cell lines, HL-60, A549, and MKN45, as well as the normal human lung cells, WI-38. Among them, N-ß-d-2-acetamido-2-deoxyglucoside (10) showed cytotoxicity against HL-60, A549, MKN45, and WI-38 cells (IC50 0.0078 - 2.8 µm). However, N-ß-d-galactoside (12) showed cytotoxicity against HL-60 and MKN45 cells (IC50 0.0021 - 4.0 µm), but not the normal WI-38 cells. Furthermore, Western blot analysis suggested that 12 induces apoptosis by activation of caspases-3, 8, and 9. These results will be useful for the synthesis of other tetracyclic triterpenoids or steroid N-glycosides to increase their cytotoxicity and apoptosis-inducing activities.

Potent Antiproliferative Effect on Liver Cancer of Medicinal Plants Selected from the Thai/Lanna Medicinal Plant Recipe Database "MANOSROI III".

Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including liver cancer. In this study, methanolic extracts (MEs) of 23 plants were tested for antiproliferative activity on human hepatoma cell line (Hep G2) by the sulforhodamine B (SRB) assay. Nine MEs with potent antiproliferative activity (IC50 < 100 µg/mL) were obtained and further semipurified by liquid/liquid partition extraction. The semipurified fractions were tested for the antiproliferative and antioxidative activities. ME of Stemona collinsae and the semipurified extract and methanol-water fraction (MF) of Gloriosa superba gave the highest antiproliferative activity on HepG2 which were 4.79- and 50.07-fold cisplatin, respectively. The semipurified fractions showed an increased antiproliferative activity. MF of Caesalpinia sappan and HF of Senna alata showed the highest free radical scavenging and metal chelating activities, respectively. The compound in n-hexane fraction (HF) of Ventilago denticulata which showed an increase in antiproliferative activity comparing to its ME was isolated and identified as emodin. This study has demonstrated the potential of the ME from S. collinsae, MF from G. superba, and emodin isolated from V. denticulata, for further development as an antiliver cancer agent.

Potent anti-proliferative effects against oral and cervical cancers of Thai medicinal plants selected from the Thai/Lanna medicinal plant recipe database "MANOSROI III".

CONTEXT: Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including oral and cervical cancers. OBJECTIVE: To investigate anti-proliferative activity on human cervical (HeLa) and oral (KB) cancer cell lines of medicinal plants selected from Thai/Lanna medicinal plant recipe database "MANOSROI III". MATERIALS AND METHODS: Twenty-three methanolic plant crude extracts were tested for phytochemicals and anti-proliferative activity on HeLa and KB cell lines for 24 h by the sulforhodamine B (SRB) assay at the doses of 1 × 10(1)-1 × 10(-6 )mg/ml. The nine extracts with the concentrations giving 50% growth inhibition (GI50) lower than 100 µg/ml were further semi-purified by liquid/liquid partition in order to evaluate and enhance the anti-proliferative potency. RESULTS: All extracts contained steroids/triterpenoids, but not xanthones. The methanolic extracts of Gloriosa superba L. (Colchinaceae) root and Albizia chinensis (Osbeck) Merr. (Leguminosae-Mimosoideae) wood gave the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.91 (6.0- and 0.31-fold of cisplatin and doxorubicin) and 0.16 µg/ml (28.78- and 82.29-fold of cisplatin and doxorubicin), respectively. Hexane and methanol-water fractions of G. superba exhibited the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.15 (37- and 1.9-fold of cisplatin and doxorubicin) and 0.058 µg/ml (77.45- and 221.46-fold of cisplatin and doxorubicin), respectively. DISCUSSION AND CONCLUSION: This study has demonstrated the potential of plants selected from MANOSROI III database especially G. superba and A. chinensis for further development as anti-oral and cervical cancer agents.

In vitro anti-proliferative activity on colon cancer cell line (HT-29) of Thai medicinal plants selected from Thai/Lanna medicinal plant recipe database "MANOSROI III".

ETHNOPHARMACOLOGICAL RELEVANCE: Thai/Lanna region has its own folklore wisdoms including the traditional medicinal plant recipes. Thai/Lanna medicinal plant recipe database "MANOSROI III" has been developed by Prof. Dr. Jiradej Manosroi. It consists of over 200,000 recipes for all diseases including cancer. To investigate the anti-proliferative and apoptotic activities on human colon cancer cell line (HT-29) as well as the cancer cell selectivity of the methanolic extracts (MEs) and fractions of the 23 selected plants from the "MANOSROI III" database. MATERIALS AND METHODS: The 23 selected plants were extracted with methanol under reflux and evaluated for their anti-proliferative activity by sulforhodamine B assay. The 5 plants (Gloriosa superba, Caesalpinia sappan, Fibraurea tinctoria, Ventilago denticulata and Psophocarpus tetragonolobus) with potent anti-proliferative activity were fractionated by liquid-liquid partition to give 4 fractions including each hexane (HF), methanol-water (MF), n-butanol (BF) and water (WF) fractions. They were tested for anti-proliferative activity and cancer cell selectivity. The ME and fractions of G. superba which showed potent anti-proliferative activity were further examined for morphological changes and apoptotic activities by acridine orange (AO)/ethidium bromide (EB) staining. RESULTS: The ME of G. superba root showed active with the highest anti-proliferative activity at 9.17 and 1.58 folds of cisplatin and doxorubicin, respectively. After liquid-liquid partition, HF of V. denticulata, MFs of F. tinctoria, V. denticulata and BF of P. tetragonolobus showed higher anti-proliferative activities than their MEs. The MF of G. superba indicated the highest anti-proliferative activity at 7.73 and 1.34 folds of cisplatin and doxorubicin, respectively, but only 0.86 fold of its ME. The ME and HF, MF and BF of G. superba and MF of F. tinctoria demonstrated high cancer cell selectivity. At 50 µg/ml, ME, HF, MF and BF of G. superba demonstrated higher apoptotic activities than the two standard drugs. CONCLUSIONS: This present study has not only confirmed the traditional use of the Thai/Lanna medicinal plant recipes for cancer treatments, but also the potential of the selected plant, G. superba for the further development as a modern anti-cancer drug.

Limonoids and flavonoids from the flowers of Azadirachta indica var. siamensis, and their melanogenesis-inhibitory and cytotoxic activities.

A new limonoid, 7-O-acetyl-7-O-debenzoyl-22-hydroxy-21-methoxylimocinin (2), and two new flavonoids, 3'-(3-hydroxy-3-methylbutyl)naringenin (7) and 4'-O-methyllespedezaflavanone C (9), along with nine known compounds, including two limonoids, 1 and 3, and seven flavonoids, 4-6, 8, and 10-12, were isolated from a MeOH extract of the flowers of Azadirachta indica A.Juss. var. siamensis Valeton (Siamese neem tree; Meliaceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. All of these compounds were evaluated for their melanogenesis-inhibitory activities in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH). Compound 2 (16.9% melanin content at 30 µM), 6-deacetylnimbin (3; 49.6% melanin content at 100 µM), and kaempferide (10; 41.7% melanin content at 10 µM) exhibited inhibitory effects with no, or almost no, toxicity to the cells (81.0-111.7% cell viability). In addition, evaluation of their cytotoxic activities against HL60, A549, AZ521, and SK-BR-3 human cancer cell lines, isoazadironolide (1), 4'-O-methyl-8-prenylnaringenin (5), euchrestaflavanone A (8), 9, and 3-methoxy-3'-prenylnaringenin (12) revealed potent cytotoxicities against one or more cell lines with IC50 values in the range of 4.5-9.9 µM.

Cancer chemopreventive effect of bergenin from Peltophorum pterocarpum wood.

The aqueous extract of Peltophorum pterocarpum (Fabaceae) wood exhibited potent inhibitory effects against EpsteinBarr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and against melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 melanoma cells, as well as potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging activity. Two phenolic acid derivatives, bergenin (1) and gallic acid (2), were isolated from the ethyl acetate (AcOEt)-soluble fraction obtained from the extract. Compound 1 exhibited potent inhibitory effect against EBV-EA activation and against skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. Both compounds 1 and 2 exhibited melanogenesis-inhibitory activities in α-MSH-stimulated B16 melanoma cells, and, in addition, compound 2 showed strong DPPH radical-scavenging activity.

Potent anti-cervical cancer activity: synergistic effects of Thai medicinal plants in recipe N040 selected from the MANOSROI III database.

ETHNOPHARMACOLOGICAL RELEVANCES: One of the prestigious Thai/Lanna folklore wisdoms is the medicinal plant recipes. Thai/Lanna medicinal plant recipe database MANOSROI III has been developed by Prof. Dr. Jiradej Manosroi. It consists of over 200,000 recipes covering all diseases including cancer. AIM OF THIS STUDY: To investigate the in vitro and in vivo anti-cervical cancer activity and the active constituents of the Thai medicinal plant recipe N040 selected from the MANOSROI III database. MATERIALS AND METHODS: The extracts of recipe N040 and single medicinal plants in the recipe were prepared by hot water and methanol extraction, respectively. The n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and water fractions of Caesalpinia sappan, the plant which showed the highest anti-proliferative activity were prepared by liquid-liquid partition extraction. The fraction which showed the highest anti-proliferative activity was further isolated for active constituents. Anti-proliferative activity of recipe N040, methanolic extracts, fractions of Caesalpinia sappan and brazilin, an active constituent on HeLa cell were investigated using sulforhodamine B (SRB) assay. Anti-oxidative activities including free radical scavenging and metal ion-chelating activities, as well as the phenolic and flavonoid contents of these fractions were also determined. The in vivo anti-cancer activity of recipe N040 on HeLa cell xenograft and the subchronic toxicity were performed in nude mice and rats, respectively. RESULTS AND CONCLUSIONS: N040 showed the potent in vitro anti-proliferative activity on HeLa cell with the IC50 value of 0.11 µg/ml. Phytochemicals detected in the plants were steroids/triterpenoids, tannins, flavonoids, saponins and alkaloids. For the single plant, methanolic extract of Caesalpinia sappan gave the highest anti-proliferative activity with the IC50 of 33.46 µg/ml. EtOAc fraction of Caesalpinia sappan showed the highest anti-proliferative and free radical scavenging activities with the IC50 and SC50 of 17.81 and 21.95 µg/ml which were 1.88 and 0.83 folds of its methanolic extract and ascorbic acid, respectively. Poor metal chelating activity (MC50>500 µg/ml) was observed in methanolic extract and all fractions. The highest phenolic and flavonoid contents were observed in the methanolic extract. Brazilin, the known compound isolated from the EtOAc fraction exhibited potent anti-proliferative activity with the IC50 of 0.28 µg/ml which was higher than its methanolic extract and EtOAc fraction of 119.50 and 63.61 folds, respectively, but only 0.39 fold of the recipe extract N040. The tumor size of the HeLa cell xenograft nude mice treated with the recipe N040 at the dose of 44.50mg/kg body weight per day was significantly smaller (p<0.05) than that of the control with the relative tumor weight inhibition of 57.23% which was 0.65 fold of cisplatin. In the subchronic toxicity study, N040 given orally at the dose of 1000 mg/kg body weight per day for 90 days showed no alteration in body weight gain, hematology [except the increase mean corpuscular hemoglobin (MCH) in the treated male rats] and clinical blood chemistry (except the increase blood glucose in the treated male rats) both in female and male rats. Only minor lesions of the organs including lung, liver, kidney and small intestine were observed in both sexes. This study has demonstrated the synergistic effect of the plants composed in the recipe which resulted in the potent anti-cancer activity and confirmed the traditionally use of the recipe N040. In addition, this study has also suggested the compound brazilin isolated from Caesalpinia sappan for its high potential to be further investigated as a novel anti-cervical cancer drug.

Antioxidative and melanogenesis-inhibitory activities of caffeoylquinic acids and other compounds from moxa.

The MeOH extract of moxa, the processed leaves of Artemisia princeps PAMP. (Asteraceae), exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and melanogenesis-inhibitory activity in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 melanoma cells. Eight caffeoylquinic acids, 1 and 6-12, five flavonoids, 13-17, two benzoic acid derivatives, 18 and 19, three coumarin derivatives, 20-22, four steroids, 23-26, and six triterpenoids, 27-32, were isolated from the MeOH extract. Upon evaluation of compounds 1, 6-23, and four semisynthetic caffeoylquinic acid esters, 2-5, for their DPPH radical-scavenging activity, 15 compounds, 1-13, 17, and 19, showed potent activities (IC(50) 3.1-16.8 µM). The 15 compounds exhibited, moreover, potent inhibitory activities (51.1-92.5% inhibition) against peroxidation of linoleic acid emulsion at 10 µg/ml concentration. In addition, when 27 compounds, 1-8, 10, 12, 13, 15-18, 20-25, and 27-32, were evaluated for their inhibitory activity against melanogenesis in α-MSH-stimulated B16 melanoma cells, five caffeoylquinic acids, i.e., chlorogenic acid (1), ethyl chlorogenate (3), propyl chlorogenate (4), isopropyl chlorogenate (5), and butyl chlorogenate (6), along with homoorientin (17) and vanillic acid (18), exhibited inhibitory activities with 33-62% reduction of melanin content at 100 µM concentration with no or almost no toxicity to the cells (89-114% of cell viability at 100 µM). Western blot analysis showed that compound 6 reduced the protein levels of microphtalmia-associated transcription factor (MITF), tyrosinase, tyrosine-related protein 1 (TRP-1), and TRP-2 mostly in a concentration-dependent manner, suggesting that this compound inhibits melanogenesis on α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase, TRP-1, and TRP-2. Furthermore, four compounds, 13, 15, 16, and 30, exhibited cytotoxicities against HL60 human leukemia cell line (IC(50) 7.0-11.1 µM), and nine compounds, 14-16, 23, 26-28, 31, and 32, showed inhibitory effects (IC(50) 272-382 mol ratio/32 pmol 12-O-tetradecanoylphohrbol-13-acetate (TPA)) against Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA in Raji cells.

Melanogenesis-inhibitory activity of aromatic glycosides from the stem bark of Acer buergerianum.

A new benzyl glucoside, 3-O-demethylnikoenoside (1), along with eleven known compounds, including seven aromatic glycosides, 2-8, three lignans, 9-11, and one cyclitol, 12, were isolated from the BuOH-soluble fraction of a MeOH extract of Acer buergerianum stem bark. The structures of the new compound were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of compounds 1-12 on melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), three compounds, i.e., hovetrichoside B (8), pinoresinol 4-O-ß-D-glucopyranoside (9), and pinoresinol 4-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (10), have been found to exhibit inhibitory effects with 41-49% melanin content compared to the control at 100 µM and low cytotoxicity to the cells (81-92% cell viability at 100 µM). Western blot analysis showed that compound 8 reduced the protein levels of MITF (=microphtalmia-associated transcription factor) and tyrosinase, in a concentration-dependent manner, suggesting that 8 inhibits melanogenesis in α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase. On the other hand, upon Western blotting, compound 9 was found to reduce the protein levels of tyrosinase and TRP-2, while it increased MITF and TRP-1 (=tyrosine-related protein 1), in a concentration-dependent manner, indicating that 9 inhibits melanogenesis in α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of tyrosinase and TRP-2.

Melanogenesis-inhibitory and cytotoxic activities of diarylheptanoids from Acer nikoense bark and their derivatives.

Nine cyclic diarylheptanoids, 1-9, including two new compounds, i.e., 9-oxoacerogenin A (8) and 9-O-ß-D-glucopyranosylacerogenin K (9), along with three acyclic diarylheptanoids, 10-12, and four phenolic compounds, 13-16, were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K (17) and D-glucose. Two of the cyclic diarylheptanoids, acerogenin A (1) and (R)-acerogenin B (5), were converted to their ether and ester derivatives, 18-24 and 27-33, respectively, and to the dehydrated derivatives, 25, 26, 34, and 35. Upon evaluation of compounds 1-16 and 18-35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α-melanocyte-stimulating hormone (α-MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2-4, 6, 9, and 12, and two phenolic glycosides, 15 and 16, exhibited inhibitory activities with 24-61% reduction of melanin content at 100 µM concentration with no or almost no toxicity to the cells (88-106% of cell viability at 100 µM). In addition, when compounds 1-16 and 18-35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11, ten ether and ester derivatives, 18-22 and 27-31, and two dehydrated derivatives, 34 and 35, exhibited potent cytotoxicities against HL60 human leukemia cell line (IC(50) 8.1-19.3 µM), and five compounds, 10, 11, 20, 29, and 30, against CRL1579 human melanoma cell line (IC(50) 10.1-18.4 µM).

Anti-inflammatory and anti-tumor-promoting effects of 5-deprenyllupulonol C and other compounds from Hop (Humulus lupulus L.).

A new phloroglucinol derivative, 5-deprenyllupulonol C (1), along with four other phloroglucinol derivatives, 2-5, five chalcones, 6-10, four flavanones, 11-14, two flavonol glycosides, 15 and 16, and five triterpenoids, 17-21, were isolated from the female inflorescence pellet extracts of hop (Humulus lupulus L.). Upon evaluation of these compounds against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, twelve compounds, i.e., 1-4, 11-14, 17-19, and 21, showed potent inhibitory effects on EBV-EA induction, with IC50 values in the range of 215-393 mol ratio/32 pmol TPA. In addition, eleven compounds, i.e., 1-4, 6, 11, 12, 14, 17, 18, and 20, were found to inhibit TPA-induced inflammation (1 µg/ear) in mice, with ID50 values in the range of 0.13-1.06 µmol per ear. Further, lupulone C (2) and 6-prenylnaringenin (14) exhibited inhibitory effects on skin-tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and with TPA as promoter.

Comparison of anti-scatter grids for digital imaging with use of a direct-conversion flat-panel detector.

Our purpose in this study was to establish a selection standard for anti-scatter grids for a direct conversion flat-panel detector (FPD) system. As indices for grid evaluation, we calculated the selectivity, Bucky factor, and the signal-to-noise ratio improvement factor (SIF) by measuring rates of scatter transmission, primary transmission, and total transmission (based on the digitally displayed measurement values of the FPD system), using 4 acrylic phantoms of different thicknesses. The results showed that the SIF was less than 1.0 when the phantom thickness was 5 cm. When the phantom thickness was 25 cm and the grid ratio was 16:1, the SIF was 1.505 and 1.518 (maximum value) at 90 and 120 kV, respectively. Compared with the grid ratio of 12:1, the SIF at the grid ratio 16:1 was improved by 6.1% at 90 kV, and by 7.0% at 120 kV. In a direct-conversion FPD system, the grid ratio of 16:1 is considered adequate for eliminating the scattered-radiation effect when much scattered radiation is present, such as with a thick imaged object or a high X-ray tube voltage.

Structural noise from automatic exposure control device and its relationship to X-ray tube voltage used for calibration of a flat-panel detector system.

In flat-panel detector (FPD) systems, the ion-chamber dosimeters used for automatic exposure control (AEC), which are placed between the detector and the source, should not affect clinical images because of FPD gain correction, but can sometimes still introduce fixed-pattern noise. In this study, we investigated whether such artifacts were caused by structural noise from the AEC detector on the basis of the noise power spectrum (NPS) and the mean square error (MSE) of FPD images taken at various tube voltages either with or without the AEC detector. When the NPS was measured without the AEC detector, the NPS did not increase in the low special-frequency band at all radiation qualities tested, irrespective of X-ray calibration tube voltages. However, when the NPS was measured while the AEC detector was used, the NPS increased in the low special-frequency band at all radiation qualities when the X-ray calibration tube voltages were at low levels. Similarly, the MSE increased when the X-ray calibration tube voltages were at low levels. From these results, artifacts in the AEC detector appear to be suppressed when a radiation quality of approximately 90 kV is used at four different standardized radiations quality (RQA3, RQA5, RQA7, and RQA9).

Osteogenic activity of diphenyl ether-type cyclic diarylheptanoids derived from Acer nikoense.

Osteogenic activity of six diarylheptanoids, acerogenin A (1), (R)-acerogenin B (2), aceroside I (3), aceroside B(1) (4), aceroside III (5) and (-)-centrolobol (6) and two phenolic compounds; (+)-rhododendrol (7) and (+)-cathechin (8), isolated from the stem bark of Acer nikoense (Nikko maple) was evaluated using alkaline phosphatase (ALP) activity as a marker for early osteoblast differentiation. We found that the diphenyl ether-type cyclic diarylheptanoids 1-5 promoted ALP activity in mouse preosteoblastic MC3T3-E1 cells without affecting cell proliferation, but linear-type diarylheptanoid 6 and phenolic compounds 7 and 8 did not. Diphenyl ether-type cyclic diarylheptanoids 1-4 also increased protein production of osteocalcin, a late stage maker for osteoblast differentiation, and induced osteoblastic mineralization. Structure-activity relationships of these compounds demonstrated that the stimulative efficacy of aglycones was higher than that of its glycosides. Taken together, diphenyl ether-type cyclic diarylheptanoids promote early- and late-stage osteoblastogenesis, which may open the possibility for the development of novel osteogenic agents.

3-O-(E)-p-coumaroyl tormentic acid from Eriobotrya japonica leaves induces caspase-dependent apoptotic cell death in human leukemia cell line.

Eleven triterpene acids, 1-11, isolated from the leaves of Eriobotrya japonica, were evaluated for inhibition of DNA topoisomerase (Topo) I and cytotoxicity against human leukemia (HL60) and melanoma cell lines (CRL1579). Among the compounds tested, four compounds, δ-oleanolic acid (4), ursolic acid (5), 3-O-(E)-p-coumaroyl tormentic acid (8), and betulinic acid (10), exhibited potent Topo I inhibitory activity (IC(50) 20.3-36.5 µM) and cytotoxicity against HL60 (EC(50) 5.0-8.1 µM). Upon assessing the apoptosis-inducing activity in HL60 cells, compound 8 exhibited induction of apoptosis detected by the observation of DNA fragmentation and membrane phospholipid exposure in flow cytometry. Western blot analysis showed that compound 8 markedly reduced the levels of procaspases-3 and 9, while being increased the levels of cleaved caspases-3 and 9. On the other hand, compound 8 exerted almost no influence on the expression of caspase-8. In addition, compound 8 increased significantly Bax/Bcl-2 ratio and activated caspase-2. These results suggested that compound 8 induced apoptotic cell death in HL60 via mainly mitochondrial pathway by, at least in part, Topo I inhibition. Therefore, compound 8 may be promising lead compound for developing an effective drug for treatment of leukemia.