An efficient method for identifying natural common homoisoflavonoid by 1H-NMR.

Homoisoflavone contains 16 carbon atoms in the skeleton. The homoisoflavonoid skeleton from natural products can be roughly divided into 13 kinds, among which 5 kinds of common skeletons contain a large amount of compounds and 8 kinds of abnormal skeletons comprise a small amount of compounds. In this article, the structure identification experience of homoisoflavonoids found in Caesalpinia mimosoides was used as references and an efficient 1H NMR spectroscopic method for identifying homoisoflavonoid structure has been established. Using the chemical shift differences of H-2, 3, 4 and 9, the common natural homoisoflavonoids can be quickly and conveniently determined.

Euphorfiatnoids A-I: Diterpenoids from the roots of Euphorbia fischeriana with cytotoxic effects.

Nine previously undescribed diterpenoids, euphorfiatnoids A-I, together with seven known diterpenoids, were isolated from the roots of wild Euphorbia fischeriana. Their structures were elucidated by the interpretation of HRESIMS, UV, and NMR data. Their configurations were determined by electronic circular dichroism (ECD) spectroscopy analysis and the structure of euphorfiatnoid A was confirmed by X-ray crystallography. To further understand the antitumor effects of E. fischeriana, we tested the cytotoxicity of these compounds against H460, HepG2, and MCF-7 cell lines in vitro using MTT assays. Euphorfiatnoid B exhibited the most promising inhibitory effect against H460 cells with an IC50 value of 9.97 µM. Euphorfiatnoid A and C also exhibited moderate cytotoxicity against HepG2 cells with IC50 values of 11.64 and 13.10 µM, respectively.

Complete mitogenome of the entomopathogenic fungus Orbiocrella petchii.

In this study, the complete mitogenome of an entomopathogenic fungus Orbiocrella petchii (syn. Torrubiella petchii) was assembled and annotated. This circular mitogenome was 23,794 bp in length and consisted of 2 rRNA genes (rnl and rns), 25 tRNA genes, and 14 standard protein-coding genes of the oxidative phosphorylation system. Two group I introns were identified, and they encoded ribosomal protein S3 (in rnl) or a GIY-YIG endonuclease (in nad1). Phylogenetic analysis based on mitochondrial DNA sequences confirms O. petchii in the family of Clavicipitaceae.

A natural chalcone induces apoptosis in lung cancer cells: 3D-QSAR, docking and an in vivo/vitro assay.

This study was to study the antitumor effect of lonchocarpin (34) from traditional herbal medicine Pongamia pinnata (L.) Pierre and to reveal the underlying mechanism. The cytotoxic activities of lonchocarpin were evaluated in 10 lung cancer cell lines and it exhibited 97.5% activity at a dose of 100 µM in the H292 cell line. A field-based quantitative structure-activity relationship (3D-QSAR) study of 37 flavonoids from P. pinnata was also performed, and the results obtained showed that the hydrophobic interaction could be the crucial factor for the antitumor activity of lonchocarpin. Molecular docking studies revealed that lonchocarpin bound stably to the BH3-binding groove of the Bcl-2 protein with hydrophobic interactions with ALA146. Also, lonchocarpin significantly reduced cell proliferation via modulating Bax/Caspase-9/Caspase-3 pathway. An apoptotic test using flow cytometry showed that lonchocarpin produced about 41.1% and 47.9% apoptosis after treatment for 24 h and 48 h, respectively. Moreover, lonchocarpin inhibited tumor growth in S180-bearing mice with an inhibition rate of 57.94, 63.40 and 72.51%, respectively at a dose of 25, 50 and 100 mg/kg. These results suggest that lonchocarpin is a potentially useful natural agent for cancer treatment.

Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis.

The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E) staining and Masson Trichrome (MT) examination. The expression of transforming growth factor-ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-ß1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis.

Calcium-activated potassium channel activator down-regulated the expression of tight junction protein in brain tumor model in rats.

This study was performed to investigate the mechanism of the blood-brain tumor-barrier (BTB) permeability increase, which was induced by NS1619, a selective K(Ca) channel activator. Using a rat brain glioma (C6) model, we exam the expression of ZO-1 and occludin in mRNA and protein level at different time point after intracarotid infusion of NS1619 (30 µg/kg/min) to tumor sites via RT-PCR and Western blot analysis. The mRNA and protein expression of ZO-1 and occludin had no great change before infusion and began to decrease significantly after 2 h NS1619 infusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG). In addition, MPG also significantly inhibited the increase of BTB permeability and malonaldehyde (MDA) level induced by NS1619. This led to the conclusion that NS1619 could time-dependently increase the BTB permeability by down-regulating the expression of tight junction protein, and this effect could be reversed by ROS.

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs.

AIM: The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs. METHODS: The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters were calculated using the Topfit 2.0 program. RESULTS: The pharmacokinetic results showed that AUC(0-t) (23.9+/-8.26 microg.h.mL(-1)) in plasma after oral administration was significantly higher than after transdermal delivery (1.00+/-0.43 microg.h.mL(-1)). In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration. CONCLUSION: The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.Acta Pharmacologica Sinica (2009) 30: 1060-1064; doi: 10.1038/aps.2009.73; published online 8 June 2009.

Anxiolytic-like effects of oleamide in group-housed and socially isolated mice.

Oleamide (cis-9,10-octadecenoamide) is an endogenous sleep-inducing lipid and prototypic member of a new class of biological signaling molecules identified in recent years. In the present study, the anxiolytic-like effect of oleamide was studied in several experimental models of anxiety in group-housed and socially isolated mice. As the results show, socially isolated mice exhibited an anxiogenic-like profile in the elevated plus-maze test, the light/dark test, and the hole-board test, which could be significantly reversed by oleamide (10 or 20 mg/kg, i.p.). Moreover, oleamide significantly reduced the anxiety levels in grouped-housed mice. In the isolation-induced aggressive test, oleamide markedly reduced the attacking duration and increased the attacking latency. It is concluded that oleamide has an anxiolytic-like effect in socially isolated or group-housed mice, which suggests that fatty acid amides might be involved in the regulation of anxiety-related behavior in mice.

Anxiolytic effect of saponins from Panax quinquefolium in mice.

The anxiolytic effect of the saponins from Aniliaeea Panax quinquefolium L. (PQS) was studied in male mice by using a number of experimental paradigms of anxiety and compared with that of the known anxiolytic compound diazepam. Use of the elevated plus-maze test revealed that PQS (50 mg/kg, p.o.) and diazepam (2.5 mg/kg, p.o.) increased the percentage of time and entries spent in open arms. In the light/dark test, PQS (50 and 100 mg/kg, p.o.) and diazepam (2.5 mg/kg, p.o.) prolonged the time spent in the light area. In the hole-board test, PQS (50 and 100 mg/kg, p.o.) and diazepam (2.5 mg/kg, p.o.) significantly increased both head-dip counts and head-dip duration. Both PQS (50 and 100 mg/kg, p.o.) and diazepam (2.5 mg/kg, p.o.) decreased the total fighting time in the isolation-induced aggressive test. Since PQS, in contrast to diazepam, had no effect on locomotion in these tests, its side-effect profile might be considered superior to the benzodiazepines. Thus, the present findings suggest that PQS might be a potential candidate for use as an anxiolytic drug.