Jiunn-Wang Liao

Antioxidant and cognitive promotion effects of anthocyanin-rich mulberry (Morus atropurpurea L.) on senescence-accelerated mice and prevention of Alzheimer's disease.

In the present study, we evaluated the beneficial effect of mulberry extracts (ME), which are rich in phenolics and anthocyanins, on the induction of antioxidant enzymes and on the promotion of cognition in senescence-accelerated mice (SAMP). Six-month old SAMP8 and SAMR1 mice were fed a basal diet supplemented with 0.18% and 0.9% ME for consecutive 12 weeks. The results showed that the mice fed the ME supplement demonstrated significantly less amyloid beta protein and showed improved learning and memory ability in avoidance response tests. ME-treated mice showed a higher antioxidant enzyme activity and less lipid oxidation in both the brain and liver, as compared to the control mice. Furthermore, treatment with ME decreased the levels of serum aspartate aminotransferase, alanine aminotransferase, triglyceride and total cholesterol that increase with ageing. The hepatoprotective effect of ME appeared to occur through a mechanism related to regulation of the mitogen-activated protein kinases and activation of the nuclear factor-erythroid 2 related factor 2, where the latter regulates the induction of phase 2 antioxidant enzymes and reduction of oxidative damage. Overall, supplementation of ME might be advantageous to the induction of an antioxidant defense system and for the improvement of memory deterioration in ageing animals.

Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice

Abstract Understanding tissue biodistribution and clearance of zinc oxide nanoparticles (ZnO-NPs) is necessary for its risk assessment. Both fed and intraperitoneally injected ZnO-NPs (2.5 g/kg) were absorbed into circulation (within 30 min post-dosing), then biodistributed to the liver, spleen, and kidney. Intraperitoneally injected ZnO-NPs remained in serum for 72 h and could more effectively spread to the heart, lung, and testes, whereas the clearance for fed ZnO-NPs in serum began 6 h after oral administration. Compared with zinc oxide microparticles (ZnO-MPs), ZnO-NPs exhibited much higher absorptivity and tissue biodistribution in fed treatment. A greater fraction of fed ZnO-NPs localised in the liver resulted in transient histopathological lesions. However, superoxide generation and cytotoxicity were showed in vitro treatment with ZnO-NPs (above 20 μg/mL). Considering both in vitro and in vivo data, the ZnO-NPs induced acute liver toxicity which was in compliance with its absorption, biodistribution, and clearance.

Long-term Administration of Rapamycin Reduces Adiposity, but Impairs Glucose Tolerance in High-Fat Diet-fed KK/HlJ Mice

Rapamycin is an immunosuppressant drug used to prevent organ rejection in transplant patients. In this study, we investigated the metabolic effects of rapamycin in an obese animal model, KK/HlJ mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle for 42 days on a high-fat diet. Treated mice lost body weight and adiposity, reduced weight gain and retroperitoneal and epididymal fat pads/body weight, decreased serum leptin and plasma triglyceride levels and had lower liver fat concentration. However, treated mice had higher serum insulin levels and food intake. Dissection of rapamycin-treated mice revealed a marked reduction in fatty liver scores and fat cell size in retroperitoneal and epididymal adipocytes. Moreover, Western blot analysis revealed that rapamycin treatment resulted in decreasing adipophilin expression, as a marker of lipid accumulation, and reducing phosphorylation of mTOR downstream targets S6K1 compared to control group. Unfortunately, rapamycin-treated animals showed a marked decline in glucose tolerance as judged by the 180-min. area under the curve for plasma glucose levels, paralleled by increased generation of plasma reactive oxygen species. These results suggest that continual rapamycin administration may help to prevent diet-induced obesity, while prolonged use of rapamycin may exacerbate glucose intolerance.

Analgesic and anti-inflammatory activities of ethanol root extract of Mahonia oiwakensis in mice

AIMS OF THE STUDY This study investigated the anti-inflammatory and analgesic activities, and protoberberine alkaloid contents of ethanol extract of MO roots (MOR(EtOH)). MATERIALS AND METHODS The analgesic activity of MOR(EtOH) was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity of MOR(EtOH) was determined using the lambda-carrageenan-induced paw oedema model. The protoberberine alkaloid contents of MOR(EtOH) were identified by high-performance liquid chromatography (HPLC). RESULTS MOR(EtOH) (100 and 500 mg/kg) decreased the acetic acid-induced writhing responses and licking times of the second phase in the formalin test. Moreover, carrageenan-induced paw oedema was significantly reduced in a dose-dependent manner by administering MOR(EtOH) (100 and 500 mg/kg) at 3, 4, and 5h after the carrageenan injection. The serum levels of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) of MOR(EtOH)-treated mice were significantly reduced compared with those in the serum of animals administered carrageenan. Notably, MOR(EtOH) attenuated the expression of cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) and neutrophil infiltration in paw tissues injected with carrageenan. The anti-inflammatory mechanisms of MOR(EtOH) appear to be related to the inhibition of neutrophil infiltration, iNOS and COX-2 protein expression, NO release, and the decreasing TNF-alpha level in serum. The analytical results showed that the contents of berberine, palmatine and jatrorrhizine were 191.45 mg/g extract, 100.15 mg/g extract and 66.45 mg/g extract, respectively. CONCLUSION These experimental results suggest that MOR(EtOH) produced both analgesic and anti-inflammatory effects in mice and may be a candidate for the development of pharmacological agents used in the treatment of inflammatory disorders.

Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.

Ergothioneine protects against neuronal injury induced by cisplatin both in vitro and in vivo

The neuroprotective effects of ergothioneine (EGT) against cisplatin toxicity were investigated both in vitro and in vivo. For in vitro study, two types of neuronal cells, primary cortical neuron (PCN) cells and rat pheochromocytoma (PC12) cells, were incubated with EGT (0.1-10.0 μM) for 2 h followed by incubation with 0.5 μM cisplatin for 72 h. Results show that cisplatin markedly decreased the proliferation of PC12 cells and strongly inhibited the growth of axon and dendrite of PCN cells, but these effects were significantly prevented by EGT. For in vivo study, CBA mice were orally administered with 2 or 8 mg EGT/kg body weight for 58 consecutive days and were injected i.p. with 5mg cisplatin/kg body weight on days 7, 9 and 11. We found that EGT significantly restored the learning and memory deficits in mice treated with cisplatin evaluated by active and passive avoidance tests. EGT also significantly prevented brain lipid peroxidation, restored acetylcholinesterase (AChE) activity and maintained glutathione/glutathione disulfide ratio in brain tissues of mice treated with cisplatin. These results demonstrate that EGT protects against cisplatin-induced neuronal injury and enhances cognition, possibly through the inhibition of oxidative stress and restoration of AChE activity in neuronal cells.

Evaluation of hormone receptor expression for use in predicting survival of female dogs with malignant mammary gland tumors.

OBJECTIVE To evaluate the prognostic potential of expression of hormone receptors in malignant mammary gland tumors of dogs. Design-Cohort study. ANIMALS 89 female dogs with malignant mammary gland tumors and 24 female dogs with benign mammary gland tumors. PROCEDURES Female dogs with malignant (n = 89 dogs) and benign (24) mammary gland tumors were evaluated to determine the prognostic value of the expression of estrogen receptor (ER)A or the progesterone receptor (PR), as determined by use of immunohistochemical methods. RESULTS In this study, 68 (60.2%) and 88 (77.9%) of the 113 dogs with mammary gland tumors had expression of ERA and PR, respectively. Expression of ERA and PR was detected proportionately more frequently in benign tumors (23/24 [95.8%] and 24/24 [100%], respectively) than in malignant tumors (45/89 [50.6%] and 64/89 [71.9%]). Percentage of tumors with positive results for ERA and PR was significantly higher in tumors < 5 cm in diameter; as clinical stage I, II, or III; and without metastasis to lymph nodes or distant metastasis. However, only PR expression in tumor cells was significantly associated with 1-year survival after surgical removal of the tumor. Moreover, dogs with malignant tumors expressing ERA and PR had a significantly higher survival rate, compared with the rate for dogs with malignant tumors expressing ERA but not PR. CONCLUSIONS AND CLINICAL RELEVANCE These findings strongly suggested that expression of PR could be used as a prognostic factor for survival, especially in female dogs with malignant mammary gland tumors with ERA expression.

Inhibitory effects of Ganoderma lucidum on tumorigenesis and metastasis of human hepatoma cells in cells and animal models.

Metastasis is considered to be the major cause of death in patients with cancers, and hepatocellular carcinoma (HCC) is a highly metastatic cancer. Ganoderma lucidum , a well-known mushroom with various biological effects, is a functional food known to contain lucidenic acid. The objectives of this study were to investigate the anti-invasion effect of a lucidenic acid-rich G. lucidum extract (GLE) on human hepatoma HepG2 cells as well as the antiproliferative and antimetastatic effects of GLE in human hepatoma cells implanted into ICR-nu/nu mice. Phorbol-12-myristate-13-acetate (PMA)-induced invasion and matrix metalloproteinase (MMP)-9 expression levels of HepG2 cells were reduced by GLE treatment in a dose-dependent manner. The inhibitory effects of GLE on MMP-9 expression proceeded by inhibiting the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and protein kinase B in the cytosol as well as reducing activator protein-1 and nuclear factor-kappa B levels in the nucleus of HepG2 cells. In a human tumor xenograft model, a dose-response inhibition was observed in the average size, volume, and weight of tumors upon oral administration of GLE. The number of metastatic tumor-bearing mice, the number of affected organs, and the number of tumor foci as well as the MMP-2 and -9 activities in serum of mice were also significantly suppressed by oral administration of GLE. These results suggest that the lucidenic acid-rich GLE could serve as a chemopreventive agent for the tumorigenesis and metastasis of highly invasive hepatoma cells.

Essential oil from leaves of Cinnamomum osmophloeum acts as a xanthine oxidase inhibitor and reduces the serum uric acid levels in oxonate-induced mice

The xanthine oxidase (XOD) inhibitory activity and anti-hyperuricemia effect in mice of Cinnamomum osmophloeum, which is an endemic tree in Taiwan, were evaluated in this study. The results demonstrated that the essential oil of C. osmophloeum leaves presented the strongest XOD inhibition activity (IC(50)=16.3 μg/ml); however, no significant XOD inhibition activities were found in ethanolic and hot water extracts. Furthermore, among the main compounds of essential oil, the cinnamaldehyde exhibited the potent XOD inhibition activity with an IC(50)=8.4 μg/ml. Besides, the reducing serum uric acid levels in oxonate-induced mice by cinnamaldehyde were further investigated. The hyperuricemic mice were oral administrated cinnamaldehyde at a dosage of 150 mg/kg, the uric acid value in serum was reduced from 5.25±0.63 to 2.10±0.04 mg/dl, the levels of serum uric acid in mice was lowered down by 84.48% as compared to the hyperuricemic control group. Based on the results obtained in this study, cinnamaldehyde may be a potential lead compound for developing the pharmaceutic for anti-hyperuricemia agent.

Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma

BACKGROUND AND PURPOSE Shikonin exhibits a wide range of anti‐inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow‐derived dendritic cells (BM‐DCs) and on allergic reactions in a murine model of asthma.