Jieun Park

Opuntia humifusa stems lower blood glucose and cholesterol levels in streptozotocin-induced diabetic rats

The Opuntia humifusa stem (OHSt) contains high levels of antioxidants including vitamin C, flavonoids, and polyphenols that may prove beneficial in treating diabetes mellitus. The objective of this study was to examine the hypothesis that intake of the OHSt regulates blood glucose levels and hypolipidemic responses in rats with diabetes mellitus induced by injection of streptozotocin. Forty Sprague-Dawley rats (6 weeks of age) were assigned to 5 groups: normal control, rats with streptozotocin-induced diabetes mellitus (DM), DM treated with OHSt 150 mg/kg per day, DM treated with OHSt 250 mg/kg per day, and DM treated with OHSt 500 mg/kg per day. Powdered OHSt was suspended in distilled water and administered orally through the sonde once daily. After 7 weeks of treatment, the fasting blood glucose and triglyceride levels of the OHSt groups were significantly lower when compared with the DM group (P < .05). Treatment with the OHSt also resulted in a significant decrease in serum total cholesterol and low-density lipoprotein cholesterol (P < .05). Decreases in both total cholesterol and low-density lipoprotein cholesterol were accompanied by a significant increase in serum high-density lipoprotein cholesterol (P < .05). Furthermore, levels of alanine aminotransferase and aspartate aminotransferase were significantly lower in the OHSt groups than in the DM group (P < .05). In addition, a significant increase in relative beta cell volume of pancreas was observed in rats treated with 500 mg/kg of OHSt when compared with the untreated DM rats (P < .05). The overall results suggest that the OHSt possesses potential hypoglycemic and hypolipidemic activity in streptozotocin-induced diabetic rats.

Opuntia humifusa Partitioned Extracts Inhibit the Growth of U87MG Human Glioblastoma Cells

Opuntia humifusa, a member of the Cactaceae family widely distributed in the southern regions of the Korean peninsula, has potential bioactive functions and medicinal benefits. In the present study, we investigated the effect of hexane, ethyl acetate extracts and water partitioned fraction of O. humifusa on proliferation, G1 arrest and apoptosis in U87MG human glioblastoma cells. Glioblastoma cellular proliferation was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and the effects of O. humifusa partitioned extracts on cell cycle and apoptosis were analyzed by flow cytometry. Our results revealed that when U87MG cells were treated with hexane extracts and water partitioned fraction of O. humifusa, the number of viable cells decreased in a concentration-dependent manner. In addition, water partitioned fractions of O. humifusa induced G1 arrest and non-apoptotic cell death as well as significant increases in ROS production in U87MG cells. In conclusion, water partitioned fractions of O. humifusa induce G1 arrest and inhibit U87MG human glioblastoma cell proliferation.

Antiviral activity of angelicin against gammaherpesviruses

Human gammaherpesviruses including Epstein-Barr virus (EBV) and Kaposis sarcoma-associated herpesvirus (KSHV) are important pathogens as they persist in the host and cause various malignancies. However, few antiviral drugs are available to efficiently control gammaherpesvirus replication. Here we identified the antiviral activity of angelicin against murine gammaherpesvirus 68 (MHV-68), genetically and biologically related to human gammaherpesviruses. Angelicin, a furocoumarin naturally occurring tricyclic aromatic compound, efficiently inhibited lytic replication of MHV-68 in a dose-dependent manner following the virus entry. The IC50 of angelicin antiviral activity was estimated to be 28.95μM, while the CC50 of angelicin was higher than 2600μM. Furthermore, incubation with angelicin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lytic replication of human gammaherpresviruses in both EBV- and KSHV-infected cells. Taken together, these results suggest that MHV-68 can be a useful tool to screen novel antiviral agents against human gammaherepsviruses and that angelicin may provide a lead structure for the development of antiviral drug against gammaherpesviruses.

Murine gammaherpesvirus 68 encoding open reading frame 11 targets TANK binding kinase 1 to negatively regulate the host type I interferon response

ABSTRACT Upon viral infection, type I interferons, such as alpha and beta interferon (IFN-α and IFN-β, respectively), are rapidly induced and activate multiple antiviral genes, thereby serving as the first line of host defense. Many DNA and RNA viruses counteract the host interferon system by modulating the production of IFNs. In this study, we report that murine gammaherpesvirus 68 (MHV-68), a double-stranded DNA virus, encodes open reading frame 11 (ORF11), a novel immune modulator, to block IFN-β production. ORF11-deficient recombinant viruses induced more IFN-β production in fibroblast and macrophage cells than the MHV-68 wild type or a marker rescue virus. MHV-68 ORF11 decreased IFN-β promoter activation by various factors, the signaling of which converges on TBK1-IRF3 activation. MHV-68 ORF11 directly interacted with both overexpressed and endogenous TBK1 but not with IRF3. Physical interactions between ORF11 and endogenous TBK1 were further confirmed during virus replication in fibroblasts using a recombinant virus expressing FLAG-ORF11. ORF11 efficiently reduced interaction between TBK1 and IRF3 and subsequently inhibited activation of IRF3, thereby negatively regulating IFN-β production. Our domain-mapping study showed that the central domain of ORF11 was responsible for both TBK1 binding and inhibition of IFN-β induction, while the kinase domain of TBK1 was sufficient for ORF11 binding. Taken together, these results suggest a mechanism underlying inhibition of IFN-β production by a gammaherpesvirus and highlight the importance of TBK1 in DNA virus replication. IMPORTANCE Gammaherpesviruses are important human pathogens, as they are associated with various kinds of tumors. Upon virus infection, the type I interferon pathway is activated by a series of signaling molecules and stimulates antiviral gene expression. To subvert such interferon antiviral responses, viruses are equipped with multiple factors that can inhibit its critical steps. In this study, we took an unbiased genomic approach using a mutant library of murine gammaherpesvirus 68 to screen a novel viral immune modulator that negatively regulates the type I interferon pathway and identified ORF11 as a strong candidate. ORF11-deficient virus infection produced more interferon than the wild type in both fibroblasts and macrophages. During virus replication, ORF11 directly bound to TBK1, a key regulatory protein in the interferon pathway, and inhibited TBK1-mediated interferon production. Our results highlight a crucial role of TBK1 in controlling DNA virus infection and a viral strategy to curtail host surveillance.

Brief Communication: SIR-2.1-dependent lifespan extension of Caenorhabditis elegans by oxyresveratrol and resveratrol

Resveratrol (RES) has been studied for its effects on the lifespan extension of Caenorhabditis elegans, but controversy still remains on its mechanism related with SIR-2. In this study, longevity assay was performed to confirm SIR-2-dependent lifespan extension of C. elgeans with RES and oxyresveratrol (OXY), an isomer of hydroxylated RES using loss-of-function mutants of C. elegans including sir-2.1 mutant. The results showed that OXY and RES significantly (P < 0.05) extended the lifespan of C. elegans compared with the control. OXY and RES also significantly (P < 0.05) increased the mRNA expression levels of sir-2.1 and aak-2 in a dose-dependent manner and increased the protein expression levels of SIR-2.1. OXY and RES treatment extended the lifespan in daf-16 loss-of-function mutants, which suggested that lifespan extension was not occurring via the activation of DAF-16. However, OXY and RES failed to extend the lifespan in loss-of-function mutants of sir-2.1 and aak-2. Therefore, OXY and RES extend the lifespan of C. elegans by overexpression of SIR-2.1, which is related to lifespan extension through calorie restriction and the AMP-activated protein kinase (AMPK) pathway, although this process is independent of the FOXO/DAF-16 pathway.

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. Graphical abstract Ex vivo antiplatelet effect of the ethanol extract of Ramulus mori containing 6.79% oxyresveratrol. Platelet aggregation was induced by (A) ADP and (B) collagen.

Hypouricemic Effect of Ethanol Extract of Aster glehni Leaves in Potassium Oxonate-Induced Hyperuricemic Rats

The prevalence of gout is increasing worldwide, and control of serum uric acid level has been regarded as one of the therapeutic methods for gout. Inhibition of xanthine oxidase (XO) activity which can oxidize hypoxanthine to uric acid has been commonly proposed to decrease serum uric acid level. The aim of this study was to demonstrate the hypouricemic effect of ethanol extract of Aster glehni leaves (EAG) by in vitro and in vivo study in potassium oxonate (PO)-induced hyperuricemic rats. EAG possessed 132.5 ± 6.8 mg QE/g of total flavonoid and showed antioxidant activity. EAG showed in vitro and in vivo inhibitory activity against XO and significantly decreased serum uric acid level in PO-induced hyperuricemic rats without liver toxicity. These results show that EAG significantly attenuates hyperuricemia by inhibiting XO activity, which resulted in the decrease of serum uric acid level. Therefore, EAG might possess a potential therapeutic ability for improving gout.