Catalytic hydrogenolysis of larix bark proanthocyanidins in ionic liquids produces UV blockers with potential for use in cosmetics.

The bark of larix, a major tree species in the coniferous forests of China's Greater Khingan Mountains, is typically treated as waste. The bark is, however, rich in flavonoids, known as proanthocyanidins, although their high degree of polymerization and high molecular weight reduce their biological activity and potential applications. Ionic liquids, a new type of "green solvent", characterized by low vapor pressure and good stability, have been developed and used as new solvents for naturally occurring macromolecules. Here, we used 1-butyl-3-methylimidazole chloride ([BMIM]Cl) as the ionic solvent to reduce the degree of polymerization of larix bark proanthocyanidins by Pd/C-catalyzed hydrogenolysis. The optimal reaction conditions, determined using an orthogonal experimental design, were: reaction temperature, 90 °C; reaction time, 1.5 h; catalyst loading, 4 g L-1 (Pd/C: [BMIM]Cl); and hydrogen pressure, 2.5 MPa. Characterization of the reaction products by UV-Vis and IR spectroscopy and gel permeation chromatographys showed that they retained the proanthocyanidin structure. We showed that whilst both the native and depolymerized proanthocyanidins were able to block UV light when added to commercially available skin creams and sunscreens, the depolymerized proanthocyanidins were more effective at a given concentration. This study expands the applications of a new "green" ionic liquid solvent, provides a technical foundation for the low-cost depolymerization of larix bark proanthocyanidins, and also explores a potential high-value use for waste larix bark as the source of a UV-blocking additive for cosmetics.

A composite carbon-based solid acid-supported palladium catalyst (Pd/C-SO3H) for hydrogenolysis of plant-derived polymeric proanthocyanidins.

A composite catalyst, Pd/C-SO3H, has been prepared to depolymerize plant-derived polymeric proanthocyanidins (PPC). Different reaction conditions were explored and the catalyst was shown to have good performance and recyclability, as well as good thermal and acid-base stability. UV, FTIR and 1H NMR analyses showed that the depolymerization products (oligomeric proanthocyanidins, OPC) retained a condensed flavanol polyphenol structure and that the basic structural units of the polymers had not been destroyed. The antioxidant activity of the OPC was better than that of the PPC, and also better than that of 2,6-di-tert-butyl-4-methylphenol, which is widely used in industry, including as a food additive. OPC could, therefore, be developed as a commercially useful radical chain-breaking antioxidant. The preparation of Pd/C-SO3H provides an example of the design and development of a new composite catalyst that has high practical value. The study also provides a new technical route for the depolymerization of PPC and thus makes a useful contribution to the high-value utilization of renewable plant resources.

Antioxidant and Fluorescence Properties of Hydrogenolyzised Polymeric Proanthocyanidins Prepared Using SO42-/ZrO2 Solid Superacids Catalyst.

Larix bark oligomeric proanthocyanidins (LOPC) were prepared from larix bark polymeric proanthocyanidins (LPPC) by catalytic hydrogenolysis using SO42-/ZrO2 solid superacid as the catalyst. The catalyst to polymeric proanthocyanidins ratio was 0.2:1 (m/m). The LOPC, obtained after hydrogenolysis at 100 °C for 4 h under 3 MPa hydrogen pressure, retained the structural characteristics of proanthocyanidins. The average degree of polymerization was reduced from 9.50% to 4.76% and the depolymerization yield was 53.85%. LOPC has good antioxidant properties and, at the same concentration, the reducing ability of LOPC was much higher than that of LPPC. The IC50 values of LOPC for scavenging DPPH• and ABTS•+ radicals were 0.046 mg/mL and 0.051 mg/mL, respectively. LOPC is biocompatible and has fluorescent properties that are affected by external factors, such as solvent polarity, pH and the presence of different metal ions. These features indicate that LOPC could be developed as a new biological fluorescent marker. The depolymerization of low-value polymeric proanthocyanidins to provide high-value oligomeric proanthocyanidins and the development of new applications for proanthocyanidins represent significant advances.

Herpes simplex virus 1 protein kinase US3 hyperphosphorylates p65/RelA and dampens NF-κB activation.

Nuclear factor κB (NF-κB) plays important roles in innate immune responses by regulating the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation, and survival. To survive in the host cells, viruses have evolved multiple strategies to evade and subvert the host immune response. Herpes simplex virus 1 (HSV-1) bears a large DNA genome, with the capacity to encode many different viral proteins to counteract the host immune responses. In the present study, we demonstrated that HSV-1 protein kinase US3 significantly inhibited NF-κB activation and decreased the expression of inflammatory chemokine interleukin-8 (IL-8). US3 was also shown to hyperphosphorylate p65 at serine 75 and block its nuclear translocation. Two US3 mutants, K220M and D305A, still interacted with p65; however, they could not hyperphosphorylate p65, indicating that the kinase activity of US3 was indispensable for the function. The attenuation of NF-κB activation by HSV-1 US3 protein kinase may represent a critical adaptation to enable virus persistence within the host. Importance: This study demonstrated that HSV-1 protein kinase US3 significantly inhibited NF-κB activation and decreased the expression of inflammatory chemokine interleukin-8 (IL-8). US3 hyperphosphorylated p65 at serine 75 to inhibit NF-κB activation. The kinase activity of US3 was indispensable for its hyperphosphorylation of p65 and abrogation of the nuclear translocation of p65. The present study elaborated a novel mechanism of HSV-1 US3 to evade the host innate immunity.

Herpes simplex virus 1-encoded tegument protein VP16 abrogates the production of beta interferon (IFN) by inhibiting NF-κB activation and blocking IFN regulatory factor 3 to recruit its coactivator CBP.

Host cells activate innate immune signaling pathways to defend against invading pathogens. To survive within an infected host, viruses have evolved intricate strategies to counteract host immune responses. Herpesviruses, including herpes simplex virus type 1 (HSV-1), have large genomes and therefore have the capacity to encode numerous proteins that modulate host innate immune responses. Here we define the contribution of HSV-1 tegument protein VP16 in the inhibition of beta interferon (IFN-ß) production. VP16 was demonstrated to significantly inhibit Sendai virus (SeV)-induced IFN-ß production, and its transcriptional activation domain was not responsible for this inhibition activity. Additionally, VP16 blocked the activation of the NF-κB promoter induced by SeV or tumor necrosis factor alpha treatment and expression of NF-κB-dependent genes through interaction with p65. Coexpression analysis revealed that VP16 selectively blocked IFN regulatory factor 3 (IRF-3)-mediated but not IRF-7-mediated transactivation. VP16 was able to bind to IRF-3 but not IRF-7 in vivo, based on coimmunoprecipitation analysis, but it did not affect IRF-3 dimerization, nuclear translocation, or DNA binding activity. Rather, VP16 interacted with the CREB binding protein (CBP) coactivator and efficiently inhibited the formation of the transcriptional complexes IRF-3-CBP in the context of HSV-1 infection. These results illustrate that VP16 is able to block the production of IFN-ß by inhibiting NF-κB activation and interfering with IRF-3 to recruit its coactivator CBP, which may be important to the early events leading to HSV-1 infection.

The nucleolus and herpesviral usurpation.

The nucleolus is a distinct subnuclear compartment known as the site for ribosome biogenesis in eukaryotes. Consequently, the nucleolus is also proposed to function in cell-cycle control, stress sensing and senescence, as well as in viral infection. An increasing number of viral proteins have been found to localize to the nucleolus. In this article, we review the current understanding of the functions of the nucleolus, the molecular mechanism of cellular and viral protein targeting to the nucleolus and the functional roles of the nucleolus during viral infection with a specific focus on the herpesvirus family.