Toxicological Evaluation of Brassica napus Extract Containing Vanadium, Nutricultured in Jeju Water.

This study evaluated the mutagenicity and acute toxicity of the juice extract of nutricultured Brassica napus containing vanadium (BECV). The BECV was prepared by nutriculture for 7 days in Jeju water containing vanadium. The mutagenic effects of BECV were investigated using the bacterial reverse mutation test, chromosome aberration test, and micronucleus test. Based on the results of the mutagenicity test, we propose that BECV is not a mutagenicity-inducing agent. In the acute oral toxicity study, male and female Sprague-Dawley rats were administered a single limiting dose of 0.014, 0.14, or 1.4 µg BECV/kg body weight; the rats were then observed for 7 days. No acute lethal effect was observed at the maximal dose of 1.4 µg BECV/kg body weight. In the subacute study, male and female rats were administered once daily, by oral gavage, a dose of 0.028, 0.14, and 0.7 µg/kg body weight of BECV for 28 days. No significant toxicity was observed not only hematological, biochemical, and pathological parameters but also the body and organ weights when compared to controls. The level of BECV with no observed adverse effects in male and female rats was 0.7 µg/kg body weight (concentration of vanadium in BECV) in the subacute toxicity study.

The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to Cisplatin: A Common Mechanism of Action via Centromere Protein M.

Although garlic induces apoptosis in cancer cells, it is unclear whether the effects are similar to those of cisplatin against bladder cancer (BC). Therefore, this study investigated whether garlic extracts and cisplatin show similar activity when used to treat BC. The effect of garlic on T24 BC cell line was examined in a BALB/C-nude mouse xenograft model and compared with that of cisplatin. Tissue microarray analysis and gene network analysis were performed to identify differences in gene expression by control tumors and tumors exposed to garlic extract or cisplatin. Investigation of gene expression based on tissues from 165 BC patients and normal controls was then performed to identify common targets of garlic and cisplatin. Tumor volume and tumor weight in cisplatin (0.05[Formula: see text]mg/kg)- and garlic-treated mice were significantly smaller than those in negative control mice. However, cisplatin-treated mice also showed a significant reduction in body weight. Microarray analysis of tumor tissue identified 515 common anticancer genes in the garlic and cisplatin groups ([Formula: see text]). Gene network analysis of 252 of these genes using the Cytoscape and ClueGo software packages mapped 17 genes and 9 gene ontologies to gene networks. BC (NMIBC and MIBC) patients with low expression of centromere protein M (CENPM) showed significantly better progression-free survival than those with high expression. Garlic extract shows anticancer activity in vivo similar to that of cisplatin, with no evident of side effects. Both appear to act by targeting protein-DNA complex assembly; in particular, expression of CENPM.

Garlic extract in bladder cancer prevention: Evidence from T24 bladder cancer cell xenograft model, tissue microarray, and gene network analysis.

There is a growing interest in the use of naturally occurring agents in cancer prevention. This study investigated the garlic extract affects in bladder cancer (BC) prevention. The effect of garlic extract in cancer prevention was evaluated using the T24 BC BALB/C-nude mouse xenograft model. Microarray analysis of tissues was performed to identify differences in gene expression between garlic extract intake and control diet, and gene network analysis was performed to assess candidate mechanisms of action. Furthermore, we investigated the expression value of selected genes in the data of 165 BC patients. Compared to the control group, significant differences in tumor volume and tumor weight were observed in the groups fed 20 mg/kg (p<0.05), 200 mg/kg, and 1000 mg/kg of garlic extract (p<0.01). Genes (645) were identified as cancer prevention-related genes (fold change >2 and p<0.05) by tissue microarray analysis. A gene network analysis of 279 of these genes (p<0.01) was performed using Cytoscape/ClueGo software: 36 genes and 37 gene ontologies were mapped to gene networks. Protein kinase A (PKA) signaling pathway including AKAP12, RDX, and RAB13 genes were identified as potential mechanisms for the activity of garlic extract in cancer prevention. In BC patients, AKAP12 and RDX were decreased but, RAB13 was increased. Oral garlic extract has strong cancer prevention activity in vivo and an acceptable safety profile. PKA signaling process, especially increasing AKAP12 and RDX and decreasing RAB13, are candidate pathways that may mediate this prevention effect.

Protein Expression Level of Skin Wrinkle-Related Factors in Hairless Mice Fed Hyaluronic Acid.

The aim of this study was to evaluate the wrinkle improving effect of hyaluronic acid intakes. Wrinkles were induced by exposing the skin of hairless mice to ultraviolet B (UVB) irradiation for 14 weeks. Hyaluronic acid was administered to the mice for 14 weeks including 4 weeks before experiments. Skin tissue was assayed by enzyme-linked immunosorbent assay to determine protein expression of wrinkle-related markers. The group supplemented with high concentrations of hyaluronic acid appeared significantly better than control group for collagen, matrix metalloproteinase 1, interleukin (IL)-1ß, and IL-6 assay. Transforming growth factor-ß1 (TGF-ß1) and hyaluronic acid synthase 2 (HAS-2) were not shown to be significantly different. In conclusion, hyaluronic acid administration regulated expression levels of proteins associated with skin integrity, and improved the wrinkle level in skin subjected to UVB irradiation.

An ethanol extract of Ramulus mori improves blood circulation by inhibiting platelet aggregation.

Inappropriate platelet aggregation can cause blood coagulation and thrombosis. In this study, the effect of an ethanol extract of Ramulus mori (ERM) on blood circulation was investigated. The antithrombotic activity of ERM on rat carotid arterial thrombosis was evaluated in vivo, and the effect of ERM on platelet aggregation and blood coagulation time was evaluated ex vivo. To evaluate the safety of ERM, its cytotoxicity to platelets and its effect on tail bleeding time were assessed; ERM was not toxic to rat platelets and did not prolong bleeding time. Moreover, administering ERM to rats had a significant preventive effect on carotid arterial thrombosis in vivo, and significantly inhibited adenosine diphosphate- and collagen-induced platelet aggregation ex vivo, whereas it did not prolong coagulation periods, such as prothrombin time and activated partial thromboplastin time. The results suggest that ERM is effective in improving blood circulation via antiplatelet activity rather than anticoagulation activity.

Age-related changes in the distribution of transient receptor potential vanilloid 4 channel (TRPV4) in the central nervous system of rats.

Transient receptor potential vanilloid type 4 (TRPV4) channels are expressed in the central nervous system, but their role in regulating the aging process under physiological and pathological conditions is still largely unknown. To identify age-related changes in the TRPV4 channel that contribute to the central nervous system, we investigated the distribution of TRPV4 in the brain and spinal cord regions of adult and aged rats. The expression of TRPV4 in the brain and spinal cord of adult and aged Sprague-Dawley rats was compared using immunohistochemistry performed with antibodies recognizing TRPV4 on free floating sections and western blotting analysis. TRPV4 immunoreactivity was significantly increased in the cerebral cortex, hippocampal formation, thalamus, basal nuclei, cerebellum and spinal cord of aged rats compared with adult control rats. In the cerebral cortex, TRPV4 immunoreactivity was significantly increased in pyramidal cells of aged rats. In addition, TRPV4 immunoreactivity was increased in the spinal cord, hippocampal formation, thalamus, basal nuclei and cerebellum of aged rats. This first demonstration of age-related increases in TRPV4 expression in the brain and spinal cord may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases. The exact regulatory mechanism and its functional significance require further elucidation.

Biological activities of Fructus arctii fermented with the basidiomycete Grifola frondosa.

Fructus arctii extract containing phenolic glycosides was cultured with Grifola frondosa mycelia to produce ß-glucosidase and its biological activities were studied. This ß-glucosidase converted the glycosides (arctiin and caffeic acid derivatives) into aglycones (arctigenin and caffeic acid). Fermented Fructus arctii extract (G-FAE) with G. frondosa had antioxidant and 5-lipoxygenase inhibitory activities. The photoprotective potential of G-FAE was tested in human dermal fibroblasts (HDF) exposed to ultra-violet A (UVA). It was revealed that G-FAE had an inhibitory effect on human interstitial collagenase (matrix metalloproteinase, MMP-1) expression in UVA-irradiated HDF. The treatment of UVA-irradiated HDF with G-FAE resulted in a dose-dependent decrease in the expression level of MMP-1 mRNA. G-FAE also showed notable stimulation of collagen biosynthetic activity for fibroblasts. These diverse functionalities suggest that G-FAE could be a promising cosmetic ingredient.

Anti-inflammatory effects of an ethanol extract of Angelica gigas in a Carrageenan-air pouch inflammation model.

Anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG; 50, 160, or 500 mg/kg) were investigated in a carrageenan-induced air pouch inflammation model. Injection of 1 ml of carrageenan (1%) into mouse air pouches markedly increased the exudate volume and exudate albumin concentration, which were significantly attenuated by oral pretreatment with EAG. EAG also markedly reduced carrageenan-induced infiltrations of neutrophils, monocytes, and lymphocytes, but did not influence eosinophils or basophils. Carrageenan dramatically increased levels of tumor necrosis factor-alpha and interleukin-6, which might be derived from the infiltrated cells. It also elevated nitric oxide, and slightly increased prostaglandin E(2). EAG pretreatment significantly lowered tumor necrosis factor-alpha and nitric oxide, but did not alter interleukin-6 or prostaglandin E(2) levels. These results indicate that EAG attenuates some inflammatory responses by blocking the tumor necrosis factor-alpha-nitric oxide pathway, and that EAG could be a promising anti-inflammatory drug candidate for inflammatory diseases.