FV peptide induces apoptosis in HEp 2 and HeLa cells: an insight into the mechanism of induction

The present study is an attempt to evaluate the antiproliferative potential of peptide (7.6 kDa) from lionfish (Pterios volitans) venom on cultured HEp2 and HeLa cells. Different dose of purified peptide (1, 2 and 4 μg/ml) at different time points (12, 24 and 36 hrs) were tested for antiproliferative index of the peptide. Among them, 2 μg/ml at 24 hrs was found to effectively inhibit cancer cell growth in vitro and did not cause any adverse effect on normal human lymphocytes. Apoptosis was examined by propidium iodide staining, confirmed by the expression of caspase-8 and caspase-3, down regulation of Bcl-2 expression and DNA fragmentation in treated cells, when compared to untreated HEp2 and HeLa cells. Thus fish venom peptide was found to selectively induce apoptosis in cancer cell

Ferulic Acid Alleviates Changes in a Rat Model of Metabolic Syndrome Induced by High-Carbohydrate, High-Fat Diet

Agricultural Research Development Agency Fund, the Thailand Research Fund, the Khon Kaen University Research Fund and the Invitation Research Fund, Faculty of Medicine, Khon Kaen University. Senaphan K. was supported by a scholarship (PHD/0048/2553) from the Royal Golden Jubilee PhD Program, the Thailand Research Fun

Study on the hypochlolesterolemic and antioxidative effects of tyramine derivatives from the root bark of Lycium chenese Miller

The aim of the present study was to investigate the hypocholesterolemic effect and potential of tyramine derivatives from Lycii Cortex Radicis (LCR), the root bark of lycium (Lycium chenese Miller) in reducing lipid peroxidation. The activities of enzymes, hepatic 3-hydroxy 3-methylglutaryl (HMG) CoA reductase and acyl-CoA:cholesterol acyltransferase (ACAT) and LDL oxidation were measured in vitro and animal experiments were also performed by feeding LCR extracts to rats. The test compounds employed for in vitro study were trans-N-p-coumaroyltyramine (CT) and trans-N-feruloyltyramine (FT), LCR components, N-(p-coumaroyl)serotonin (CS) and N-feruloylserotonin (FS) from safflower seeds, ferulic acid (FA) and 10-gingerol. It was observed that FT and FS at the concentration of 1.2 mg/mL inhibited liver microsomal HMG CoA reductase activity by ~40%, but no inhibition of activity was seen in the cases of CT, CS, FA and 10-gingerol. Whereas, ACAT activity was inhibited ~50% by FT and CT, 34-43% by FS and CS and ~80% by 10-gingerol at the concentration of 1 mg/mL. A significant delay in LDL oxidation was induced by CT, FT, and 10-gingerol. For the animal experiment, five groups of Sprague-Dawley male rats were fed high fat diets containing no test material (HF-control), 1 and 2% of LCR ethanol extract (LCR1 and LCR2), and 1% of extracts from safflower seed (Saf) and ginger (Gin). The results indicated that total cholesterol level was significantly lower in Saf, LCR2 and Gin groups, and HDL cholesterol level was lower only in Gin group when compared with HF-control group; while there was no difference in the serum triglyceride levels among the five experimental groups. The level of liver cholesterol was significantly lower in LCR1 and LCR2 groups than HF-control. Serum levels of TBARS were significantly lower only in LCR2 group when compared with HF-control group. From the observed results, we concluded that LCR can be utilized as a hypocholesterolemic ingredient in combination with ginger, especially for functional foods

Yokukansan Inhibits Neuronal Death during ER Stress by Regulating the Unfolded Protein Response

Recently, several studies have reported Yokukansan (Tsumura TJ-54), a traditional Japanese medicine, as a potential new drug for the treatment of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress is known to play an important role in the pathogenesis of AD, particularly in neuronal death. Therefore, we examined the effect of Yokukansan on ER stress-induced neurotoxicity and on familial AD-linked presenilin-1 mutation-associated cell death.We employed the WST-1 assay and monitored morphological changes to evaluate cell viability following Yokukansan treatment or treatment with its components. Western blotting and PCR were used to observe the expression levels of GRP78/BiP, caspase-4 and C/EBP homologous protein.Yokukansan inhibited neuronal death during ER stress, with Cnidii Rhizoma (Senkyu), a component of Yokukansan, being particularly effective. We also showed that Yokukansan and Senkyu affect the unfolded protein response following ER stress and that these drugs inhibit the activation of caspase-4, resulting in the inhibition of ER stress-induced neuronal death. Furthermore, we found that the protective effect of Yokukansan and Senkyu against ER stress could be attributed to the ferulic acid content of these two drugs.Our results indicate that Yokukansan, Senkyu and ferulic acid are protective against ER stress-induced neuronal cell death and may provide a possible new treatment for AD

PGE from Octopus aegina Induces Apoptosis in Ehrlich’s Ascites Carcinoma of Mice

The present study was carried out to assess the antitumor effect of venomous peptide from the cephalopod Octopus aegina on Ehrlich’s ascites carcinoma (EAC). Male albino Swiss mice were used in the present study. Four groups of animals were treated with three doses of the sublethal dose of venom, 15, 75, and 150 µg/kg body weight (intraperitoneal injection), along with the standard drug 5-fluorouracil (20 mg/kg b.w.). After 10 days of treatment, six animals from each group were sacrificed for the biochemical analysis and the rest were left to calculate the mean survival time. In EAC-bearing mice, mean lifespan, tumor volume, hemoglobin, red blood cells, and lymphocytes were significantly decreased when compared to the normal animals. While body weight, neutrophils, and viable tumor cell count were increased in the EACbearingmice, these changes were brought back to near normal levels in different treatment groups. Themacromolecule concentration of peritoneal cells, such as DNA, RNA, and protein, were altered in the EAC-bearingmice and observed to be near normal in the treatment groups. The caspase-3 activity was significantly increased in the peritoneal cells of the treatment groups when compared to the EAC-bearing mice. The role of apoptotic cascade in EAC cell death was confirmed by the DNA fragmentation on agarose gel. Apart from the antitumor effect, octopus venom reduced the tumor burden on the liver and altered the changes in the activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Therefore, the venom from O. aegina has a potential antitumor effect on the EAC-bearing mice

Photo-Irradiated Curcumin Supplementation in Streptozotocin-Induced Diabetic Rats: Effect on Lipid Peroxidation

Background: Diabetes mellitus is one of the most common endocrine disorders. A large number of studies are in progress to identify natural substances that are effective in reducing the severity of diabetes. Although a number of drugs are currently marketed, their long-term use can cause a number of adverse effects. Materials and methods: In the present study, we examined the effect of photo-irradiated curcumin on experimental diabetes in order to evaluate the antihyperglycaemic effects of this compound on streptozotocin (40 mg/kg bodyweight)-induced diabetes. Photo-irradiated curcumin was given at a dose of 10, 30 and 80 mg/kg bodyweight. The level of blood glucose was elevated in the diabetic animals. The liver, kidney and brain were assayed for the degree of lipid peroxidation, reduced glutathione content and the activity of enzymic and levels of non-enzymic antioxidants. Results: Antioxidant status decreased in the diabetic animals. Oral administration of photo-irradiated curcumin for 45 days resulted in a significant decrease in the levels of blood glucose, together with near normalisation of enzymic activity and the markers of lipid peroxidation. The best results were obtained in rats treated with 30 mg/kg bodyweight of photo-irradiated curcumin

Histopathological changes induced by mice after intramuscular injection of venom from spin-bellied sea snake, Lepemis curtus (Shaw, 1802)

The venom of the Lapemis curtus was tested for its ability to induce histopathological changes in mice intraperitoneal injection of the venom (LD50 of 0.65 mg kg-1), by light microscopic examination of some organs (liver, kidney and spleen). L. curtus veno0m induces changes including necrosis and edematous appearance with cellular infiltration and vacuolation. The injury of kidneys includes significant changes of the glomerular apparatus. Venom trated mice liver shows congestion, micro vesicular fatty changes and infiltration of inflammatory cells around the portal vein. Where as, spleen showed hemorrhage, congested and inflammation were observed. Areas of hemorrhage, vascular congestion and cloudy swelling in renal tubules were observed in the kidney. No myoglobinuria was noted in any group of animals. The crude venom was also administered intraperioteneally into the experimental animals and tissue samples were taken at several time intervals. The venom of the sea snake L. curtus, was tested for its ability to induce myonecrosis changes in albino mice. Induction of myonecrosis was demonstrated by their ability to release Creatine Kinase (CK) from damages muscle fibers and direct histopathological examination of the injected muscles (i.m). Crude venom exhibits intense myonecrosis characterized by the changes including, necrosis and edematous appearance with cellular infiltrate, vacuolation and degenerated muscle cells with delta lesions and heavy edema in between the cells