Anti-Inflammatory Cembranoids from a Formosa Soft Coral Sarcophyton cherbonnieri

The present investigation on chemical constituents of the soft coral Sarcophyton cherbonnieri resulted in the isolation of seven new cembranoids, cherbonolides F–L (1–7). The chemical structures of 1–7 were determined by spectroscopic methods, including infrared, one- and two-dimensional (1D and 2D) NMR (COSY, HSQC, HMBC, and NOESY), MS experiments, and a chemical reduction of hydroperoxide by triphenylphosphine. The anti-inflammatory activities of 1–7 against neutrophil proinflammatory responses were evaluated by measuring their inhibitory ability toward N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced superoxide anion generation and elastase release in primary human neutrophils. The results showed that all isolates exhibited moderate activities, while cherbonolide G (2) and cherbonolide H (3) displayed a more active effect than others on the inhibition of elastase release (48.2% ± 6.2%) and superoxide anion generation (44.5% ± 4.6%) at 30 µM, respectively.     

Efficacy of avermectin B1 given orally against equine intestinal strongyles and Onchocera microfilaria

Three groups of horses and ponies (N = 13, 13 and 12) were treated with ivermectin paste (0.2 mg/kg p.o.), avermectin B1 solution (0.2 mg/kg p.o.), or fenbendazole suspension (10 mg/kg via nasogastric tube). The avermectin B1 was a 1% solution in a propylene glycolglycerol formal base. Faecal strongyle egg counts were performed before, and 14, 28, 42, 56 and 70 d, after treatment. Full-thickness skin biopsies from the neck, pectoral and umbilical regions were examined for Onchocera microfilaria before treatment, and again 14 and 70 d later. Ivermectin therapy produced a significant (P less than 0.01) decrease in mean strongyle egg counts 14, 28, 42 and 56 d after treatment. Avermectin B1 therapy resulted in significant (P less than 0.01) decreases in mean strongyle egg counts 14, 28 and 42 d after treatment. All horses given ivermectin or avermectin B1 had zero strongyle egg counts 14 and 28 d after treatment. Fenbendazole failed to significantly decrease strongyle egg counts. Both ivermectin and avermectin B1 resulted in zero microfilaria counts in all horses 14 d after treatment. On day 70 the percentage decrease in microfilaria counts were 100% and 99.6% respectively. Fenbendazole failed to significantly decrease microfilaria counts. The oral administration of this formulation of avermectin B1 appeared to be highly efficacious against intestinal strongyles and Onchocera microfilaria. The duration of anti-strongyle activity was, however, significantly (P less than 0.01) shorter than that of ivermectin paste.     

Inhibition of reactive nitrogen species in vitro and ex vivo by trypsin inhibitor from sweet potato 'Tainong 57' storage roots

Peroxynitrite (ONOO-), formed from a reaction of superoxide and nitric oxide, is one of the most potent cytotoxic species known to oxidize cellular constituents including essential proteins, lipids, and DNA. ONOO- induces cellular and tissue injury, resulting in several human diseases such as Alzheimer's disease, atherosclerosis, and stroke. Due to the lack of endogenous enzymes responsible for ONOO- scavenging activity, finding a specific ONOO- scavenger is of considerable importance. In this study, the ability of trypsin inhibitor (TI), isolated from sweet potato storage roots (SPTI), to scavenge *ON and ONOO- was investigated. The data obtained show that TI generated a dose-dependent inhibition on production of nitrite and superoxide radicals. The IC50 value of TI on superoxide radical was 143.2 +/- 4.29 microg/mL. SOD activity staining was used to confirm SOD activity of SPTI. SPTI also caused a dose-dependent inhibition of the oxidation of dihydrorhodamine 123 (DHR) by peroxynitrite. A calculated IC50 value of 809.1 +/- 32.36 microg/mL was obtained on the inhibition of peroxynitrite radical. Spectrophotometric analyses revealed that TI suppressed the formation of ONOO--mediated tyrosine nitration through an electron donation mechanism. In further studies, TI also showed a significant ability to inhibit nitration of bovine serum albumin (BSA) in a dose-dependent manner. In vivo TI inhibited lipopolysaccharide-induced nitrite production in macrophages in a concentration-dependent manner with an IC50 value of 932.8 +/- 29.85 microg/mL. The present study suggested that TI had an efficient reactive nitrogen species scavenging ability. TI might be a potential effective NO and ONOO- scavenger useful for the prevention of NO- and ONOO--involved diseases.     

Baicalein induction of hydroxyl radical formation via 12-lipoxygenase in human platelets: an ESR study

The pro-oxidant activities of baicalein, morin, myricetin, quercetin, and rutin were examined in various cell-containing systems including human platelets, rat vascular smooth muscle cells, human umbilical vein endothelial cells (HUVECs), human THP-1 cells, and fibroblast cells. Electron spin resonance (ESR) results showed that only baicalein generated hydroxyl radicals in a resting human platelet suspension, whereas the other flavonoids showed no effects on any of the resting cell systems. A low concentration of arachidonic acid (AA) increased the intensity of hydroxyl radicals, but a high concentration inhibited it. Collagen and thrombin, platelet aggregatory agents that can cause the release of AA by platelets, enhanced baicalein-induced hydroxyl radical formation, whereas ADP and U44619 showed no significant effects. Quinacrine and 5,8,11,14-eicosatetraenoic trifluoromethyl ketone, both PLA2 inhibitors, significantly attenuated baicalein-induced hydroxyl radical formation. These results suggest that baicalein-induced hydroxyl radical formation is associated with AA metabolite enzymes in human platelets. The formation of hydroxyl radicals was significantly inhibited by lipoxygenase inhibitors including nordihydroguaiaretic acid, (-)-epicatechin, (-)-epicatechin gallate, and hinokitiol, but was not affected by desferroxamine or the heme protein inhibitors KCN and NaN3. On the other hand, semiquinone free radicals were generated when baicalein was incubated with horseradish peroxidase/H2O2 or platelets/AA. The semiquinone radicals formed in the platelets/AA system could be extensively inhibited by desferroxamine, diethylenetriaminepentaacetic acid, KCN, and NaN3, indicating that prostaglandin H synthase (PGHS)-peroxidase may be involved. The results of this study led to the proposal that baicalein induces hydroxyl radical formation via 12-lipoxygenase and induces semiquinone radical formation via PGHS-peroxidase in human platelets.     

Inhibitory Effect of Dihydroaustrasulfone Alcohol on the Migration of Human Non-Small Cell Lung Carcinoma A549 Cells and the Antitumor Effect on a Lewis Lung Carcinoma-Bearing Tumor Model in C57BL/6J Mice

There are many major causes of cancer death, including metastasis of cancer. Dihydroaustrasulfone alcohol, which is isolated from marine coral, has shown antioxidant activity, but has not been reported to have an anti-cancer effect. We first discovered that dihydroaustrasulfone alcohol provided a concentration-dependent inhibitory effect on the migration and motility of human non-small cell lung carcinoma (NSCLC) A549 cells by trans-well and wound healing assays. The results of a zymography assay and Western blot showed that dihydroaustrasulfone alcohol suppressed the activities and protein expression of matrix metalloproteinase (MMP)-2 and MMP-9. Further investigation revealed that dihydroaustrasulfone alcohol suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. Dihydroaustrasulfone alcohol also suppressed the expression of PI3K and the phosphorylation of Akt. Furthermore, dihydroaustrasulfone alcohol markedly inhibited tumor growth in Lewis lung cancer (LLC)-bearing mice. We concluded that dihydroaustrasulfone alcohol is a new pure compound with anti-migration and anti-tumor growth activity in lung cancer and might be applied to clinical treatment in the future.     

Eunicellin-Based Diterpenoids,Hirsutalins N–R,from the Formosan Soft Coral Cladiella hirsuta

New eunicellin-type hirsutalins N–R (1–5), along with two known eunicellins, (6 and 7) were isolated from the soft coral Cladiella hirsuta. The structures of the metabolites were determined by extensive spectroscopic analysis. Cytotoxic activity of compounds 1–7 against the proliferation of a limited panel of cancer cell lines was measured. The in vitro anti-inflammatory activity of compounds 1–7 was evaluated by measuring their ability in suppressing superoxide anion generation and elastase release in fMLP/CB-induced human neutrophils.     

Monitoring distances travelled by horses using GPS tracking collars

Objective The aims of this work were to (1) develop a low-cost equine movement tracking collar based on readily available components, (2) conduct preliminary studies assessing the effects of both paddock size and internal fence design on the movements of domestic horses, with and without foals at foot, and (3) describe distances moved by mares and their foals. Additional monitoring of free-ranging feral horses was conducted to allow preliminary comparisons with the movement of confined domestic horses. Procedures A lightweight global positioning system (GPS) data logger modified from a personal/vehicle tracker and mounted on a collar was used to monitor the movement of domestic horses in a range of paddock sizes and internal fence designs for 6.5-day periods. Results In the paddocks used (0.8–16 ha), groups of domestic horses exhibited a logarithmic response in mean daily distance travelled as a function of increasing paddock size, tending asymptotically towards approximately 7.5 km/day. The distance moved by newborn foals was similar to their dams, with total distance travelled also dependent on paddock size. Without altering available paddock area, paddock design, with the exception of a spiral design, did not significantly affect mean daily distance travelled. Feral horses (17.9 km/day) travelled substantially greater mean daily distances than domestic horses (7.2 km/day in 16-ha paddock), even when allowing for larger paddock size. Conclusions Horses kept in stables or small yards and paddocks are quite sedentary in comparison with their feral relatives. For a given paddock area, most designs did not significantly affect mean daily distance travelled.