Neuroprotective effect of 3,5-di-O-caffeoylquinic acid on SH-SY5Y cells and senescence-accelerated-prone mice 8 through the up-regulation of phosphoglycerate kinase-1.

As aged population dramatically increases in these decades, efforts should be made on the intervention for curing age-associated neurologic degenerative diseases such as Alzheimer's disease (AD). Caffeoylquinic acid (CQA), an antioxidant component and its derivatives are natural functional compounds isolated from a variety of plants. In this study, we determined the neuroprotective effect of 3,5-di-O-CQA on Abeta(1-42) treated SH-SY5Y cells using MTT assay. To investigate the possible neuroprotective mechanism of 3,5-di-O-CQA, we performed proteomics analysis, real-time PCR analysis and measurement of the intracellular ATP level. In addition, we carried out the measurement of escape latency time to find the hidden platform in Morris water maze (MWM), real-time PCR using senescence-accelerated-prone mice (SAMP) 8 and senescence-accelerated-resistant mice (SAMR) 1 mice. Results showed that 3,5-di-O-CQA had neuroprotective effect on Abeta (1-42) treated cells. The mRNA expression of glycolytic enzyme (phosphoglycerate kinase-1; PGK1) and intracellular ATP level were increased in 3,5-di-O-CQA treated SH-SY5Y cells. We also found that 3,5-di-O-CQA administration induced the improvement of spatial learning and memory on SAMP8 mice, and the overexpression of PGK1 mRNA. These findings suggest that 3,5-di-O-CQA has a neuroprotective effect on neuron through the upregulation of PGK1 expression and ATP production activation.

Pacovatinins A-C, new labdane diterpenoids from the seeds of Renealmia exaltata.

Three new labdane diterpenoids, pacovatinins A-C (1-3), were isolated from seeds of the Brazilian medicinal plant Renealmia exaltata ("Pacová-catinga"), and their structures including absolute configurations were elucidated by spectroscopic data and a modified Mosher method.

Porwenins A and B, new clerodane diterpenoids from Portulaca okinawensis.

Two new clerodane-type diterpenes, porwenins A (1) and B (2), were isolated from Portulaca okinawensis, and the structures were elucidated by spectroscopic data.

Echinophyllins C-F, new nitrogen-containing clerodane diterpenoids from Echinodorus macrophyllus.

Four new nitrogen-containing clerodane diterpenoids, echinophyllins C-F (1-4), were isolated from the leaves of the Brazilian medicinal plant Echinodorus macrophyllus ("Chapéu-de-couro"), and their structures and relative stereochemistry were elucidated from their spectroscopic data. Compounds 1-4 possess an alpha,beta-unsaturated gamma-lactam ring consisting of a clerodane diterpene unit and an amine moiety.

Multidrug resistance reversal activity of taxoids from Taxus cuspidata in KB-C2 and 2780AD cells.

Some non-taxol-type taxoids having neither an oxetane ring at C-4 and C-5 nor an N-acylphenyl-isoserine group at C-13, such as taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J, which were isolated from the Japanese yew Taxus cuspidata, increased cellular accu-mulation of vincristine (VCR) in multidrug-resistant 2780AD cells as potently as verapamil, and efficiently inhibited [(3)H]azidopine photolabeling of P-glycoprotein (P-gp). Taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J at 10 microM completely reversed the resistance to colchicine, VCR, and taxol in KB-C2 cells, which overexpress P-gp, while taxinine and taxinine M showed no effect. Taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J may be candidate pharmaceuticals for reversing multidrug resistance (MDR) and also may be good modifiers of MDR in cancer chemotherapy.

Coruscol A, a new metabolite from the marine-derived fungus penicillium species.

A new metabolite possessing a 1,3-dioxane ring, coruscol A (1), was isolated from the mycelium of the fungus Penicillium sp., which was separated from the Okinawan marine bivalve Mytilus coruscus, and the structure was elucidated by spectroscopic data.

Chapecoderins A-C, new labdane-derived diterpenoids from Echinodorus macrophyllus.

A new seco-labdane-type diterpenoid, chapecoderin A (1), and two new rearranged labdane-type diterpenoids, chapecoderins B (2) and C (3), were isolated from the leaves of the Brazilian medicinal plant Echinodorus macrophyllus ("Chapéu-de-couro"), and their structures and relative stereochemistry were elucidated by spectroscopic data. Chapecoderins A-C (1-3) possess in common an alpha,beta-unsaturated gamma-lactone ring in the side chain.

Sculezonones A and B, two metabolites possessing a phenalenone skeleton from a marine-derived fungus Penicillium species.

Two new metabolites possessing a phenalenone skeleton, sculezonones A (1) and B (2), were isolated from cultured broth of the fungus Penicillium sp., which was separated from the Okinawan marine bivalve Mytilus coruscus, and the structures were elucidated by spectroscopic data.

Antimitotic activity of moroidin, a bicyclic peptide from the seeds of Celosia argentea.

A unique bicyclic peptide, moroidin (1), from the seeds of Celosia argentea (Amaranthaceae) strongly inhibited the polymerization of tubulin. The stereostructure of moroidin (1) was reinvestigated by spectroscopic data, chemical degradation, and molecular dynamics simulation.

The diversity of chemical substances controlling the nyctinastic leaf-movement in plants.

Leaf-movement in nyctinastic plants has long been believed to be controlled by plant hormones that are common among all nyctinastic plants. We have identified several bioactive substances for nyctinasty, whose bioactivities were highly specific to the original plant, based on the bioassay using the original plant leaf, and have shown that nyctinastic leaf-movement is not regulated by plant hormones. Our present results are in accordance with Umrath et al. physiologically significant opinion.

Palythoalones A and B, new ecdysteroids from the marine zoanthid palythoaaustraliae

Two new ecdysteroids, palythoalones A (1) and B (2), have been isolated from the marine zoanthid Palythoa australiae. The structures have been elucidated on the basis of spectroscopic data and by chemical means.

Modulation of multidrug resistance in tumor cells by taxinine derivatives.

Among a series of taxinine (1) and its designed derivatives (2-33), two taxoids (29 and 33) increased cellular accumulation of vincristine in multidrug-resistant tumor cells more potently than verapamil, while the activities of eight taxoids (11, 14-16, 22, and 30-32) were comparable with that of verapamil. These results reveal that some taxinine derivatives are good modifiers of multidrug resistance in tumor cells.

Brasilicardin A, a new terpenoid antibiotic from pathogenic Nocardia brasiliensis: fermentation, isolation and biological activity.

A novel tricyclic diterpenoid antibiotic, brasilicardin A, was isolated from the culture broth of Nocardia brasiliensis IFM 0406. The antibiotic exhibited immunosuppressive activity in a mouse mixed lymphocyte reaction (MLR) assay system and its IC50 value was 0.057 microg/ml. Although the inhibitory activity of cyclosporin A (CyA) against IL-2 production was confirmed in the MLR assay system, brasilicardin A did not have the activity. The results of in vitro toxicity testing of brasilicardin A against various human cell lines were compared with those of CyA.

New cyclic polyketide peroxides from okinawan marine sponge plakortis sp

Three new cyclic peroxides (2-4) have been isolated from the Okinawan marine sponge Plakortis sp., and the structures were elucidated by extensive spectroscopic analyses. The absolute stereochemistries of 2 and 3 were determined by chemical conversion, whereas that of the dioxane ring of 4 was assigned by the modified Mosher's method.

Three new metabolites from the marine yeast aureobasidium pullulans

Two new diketopiperazines (1 and 2) with a d-cis-4-hydroxyproline residue, and orcinotriol (3), a new 1,3-dihydroxyphenol derivative, were isolated from cultured broth of the yeast Aureobasidium pullulans, which was isolated from an Okinawan marine sponge. The structures of the compounds, including their absolute stereochemistries, were determined by spectroscopic data and chemical means.

Modulation of multidrug resistance by taxuspine C and other taxoids from Japanese yew.

Taxuspine C (1), a new taxoid from the Japanese yew Taxus cuspidata, increasing the cellular accumulation of vincristine (VCR) in multidrug-resistant tumor cells as potent as verapamil enhanced the chemotherapeutic effect of VCR in P388/VCR-bearing mice. When taxuspine C (1) was given i.p. daily at 200 mg/kg with 0.2 mg/kg VCR for 5 days, a treated/control (T/C) value of 138% was obtained. The other new taxoids, taxezopidines G (8) and H (9), from the yew also increased the VCR accumulation as potent as verapamil. These results suggest that some taxoids may be useful for overcoming multidrug resistance in tumor cells.

Brasilinolide A, a new macrolide antibiotic produced by Nocardia brasiliensis: producing strain, isolation and biological activity.

A new 32-membered macrolide antibiotic, brasilinolide A was isolated from the fermentation broth of Nocardia sp. IFM 0406. The producer was identified as Nocardia brasiliensis. The antibiotic was only active against Aspergillus niger, but not active against other fungi including yeasts as well as other filamentous like fungi and bacteria. Brasilinolide A exerted an immunosuppressive activity in the assay system of a mixed lymphocyte reaction (MLR).

Distinctive portal venographic pattern in patients with sclerotherapy resistant oesophageal varices.

We performed prophylactic sclerotherapy in 350 patients with 'high risk' oesophageal varices (F2 or F3 with a moderate or severe red colour sign). Of these patients, eight exhibited sclerotherapy resistance (i.e. no significant reduction in the size of varices after five sessions of sclerotherapy). Thus, the prevalence of sclerotherapy resistant varices was 2%. Of 350 patients, 97 underwent haemodynamic investigation before sclerotherapy. This group consisted of seven patients with sclerotherapy resistant varices and 90 patients with non-resistant varices. Portal pressure, assessed by portal venous pressure gradient, was similar in these two groups (21.5 +/- 4.8 vs 19.8 +/- 5.0 mmHg, respectively; NS). However, the prevalence of the 'pipe-line' form of variceal feeding pattern (a large dilated left gastric vein running up the oesophagus) was higher in patients with resistant varices than in those with non-resistant varices (100 vs 3%, respectively; P < 0.01) and the diameter of the left gastric vein was larger in patients with resistant varices than in those with non-resistant varices (12.4 +/- 2.0 vs 7.8 +/- 2.3 mm, respectively; P < 0.01). Moreover, the extravariceal portosystemic shunt was poorly developed in patients with resistant varices compared with non-resistant varices (0 vs 52%, respectively; P < 0.05). We conclude that the pipe-line pattern, fed by a large left gastric vein and associated with poorly developed extravariceal portosystemic shunt, is a distinctive portal venographic feature of sclerotherapy resistant varices.

Effect of vasopressin on esophageal varices blood flow in patients with cirrhosis: comparisons with the effects on portal vein and superior mesenteric artery blood flow.

BACKGROUND/AIMS: Vasopressin reduces portal pressure which may be due to decreased portal inflow. However, it remains unclear whether vasopressin is able to selectively reduce esophageal varices blood flow. The aim of this study was to address this question. METHODS: Fifteen patients with cirrhosis and esophageal varices were included in this prospective study. Portal vein and superior mesenteric artery flow velocity were measured with a percutaneous echo-Doppler. Esophageal varices flow velocity was measured using a transesophageal echo-Doppler technique. Mean arterial pressure and heart rate were also recorded. These measurements were performed at baseline condition and 15 min after observer blind drug administration. In this study, two groups, six patients receiving placebo and nine patients receiving 0.3 U/min of vasopressin, were randomized according to the coded number. RESULTS: Placebo administration had no effect on systemic and splanchnic circulation. In contrast, vasopressin administration increased mean arterial pressure (p < 0.05) associated with a bradycardia (p < 0.01). In splanchnic circulation, vasopressin decreased portal vein (-32 +/- 3%, p < 0.01), superior mesenteric artery (-30 +/- 2%, p < 0.01), and esophageal varices flow velocity (-48 +/- 5%, p < 0.01). When the magnitude of these reductions was compared, ANOVA showed a significant difference (p < 0.01). Furthermore, the reduction in esophageal varices flow velocity was significantly higher than that in portal vein flow velocity (p < 0.01) and that in superior mesenteric artery flow velocity (p < 0.01). CONCLUSIONS: These data support the view that vasopressin is able to selectively reduce esophageal varices blood flow. This effect, in addition to its well-established portal pressure reducing action, may play a role in its therapeutic efficacy in the treatment of variceal bleeding.