Search

Two new isoindolin-1-ones (1 and 2), were isolated from the stems of Nicotiana tabacum (a cultivar of sun-cured tobacco with high resistance to black shank diseases, which originated from Huize local sun-cured tobacco by ethyl methanesulfonate mutagenesis). Their structures were elucidated using spectroscopic methods, including extensive 1D and 2D NMR techniques. Interestingly, both compounds showed high antibacterial activity with bacteriostatic diameter within the range 18.2 ± 1.4–25.8 ± 2.2 mm against five pathogenic strains, and they have the potential values for use as an antiseptic agent for Heat Not Burning cigarette-tipping paper. [ABSTRACT FROM AUTHOR]

Rosiglitazone is an agonist of peroxisome proliferator-activated receptor- (PPAR-) γ that is principally associated with insulin action. The exact mechanisms underlying its insulin-sensitizing action are still not fully elucidated. It is well known that adiponectin mostly secreted in adipose tissue is an insulin sensitizer. Here, we found that treatment of Otsuka Long-Evans Tokushima Fatty (OLETF) rats with rosiglitazone (3 mg/kg, once daily, by oral gavage for 33 weeks) attenuated the increase in fasting plasma insulin concentrations and the index of the homeostasis model assessment of insulin resistance along with the age growth and glucose concentrations during an oral glucose tolerance test. In addition, the increase in plasma alanine aminotransferase activity, concentrations of fasting plasma nonesterified fatty acids and triglyceride, and hepatic triglyceride content was also suppressed. The hepatic protein expression profile revealed that rosiglitazone increased the downregulated total protein expression of insulin receptor substrate 1 (IRS-1) and IRS-2. Furthermore, the treatment suppressed the upregulated phosphorylation of IRS-1 at Ser307 and IRS-2 at Ser731. The results indicate that rosiglitazone ameliorates hepatic and systemic insulin resistance, hepatic inflammation, and fatty liver. Mechanistically, rosiglitazone suppressed hepatic protein overexpression of both phosphorylated nuclear factor- (NF-) κBp65 and inhibitory-κB kinase-α/β, a transcription factor that primarily regulates chronic inflammatory responses and the upstream NF-κB signal transduction cascades which are necessary for activating NF-κB, respectively. More importantly, rosiglitazone attenuated the decreases in adipose adiponectin mRNA level, plasma adiponectin concentrations, and hepatic protein expression of adiponectin receptor-1 and receptor-2. Thus, we can draw the conclusion that rosiglitazone elicits an adiponectin-mediated insulin-sensitizing action at the adipose tissue-liver axis in obese rats. Our findings may provide new insights into the mechanisms of action of rosiglitazone. [ABSTRACT FROM AUTHOR]

Abstract: Protease-activated receptor-2 (PAR2) has been shown to play a key role in the pathophysiology of itch. However, the precise mechanism of PAR2-mediated itch remains largely unknown. In the present study, we investigated the effects of several agents on the scratching behavior induced by PAR2-activating peptide (SLIGRL-NH2). Pretreatment of experimental animals with tacrolimus or the 5-lipoxygenase inhibitor zileuton significantly reduced SLIGRL-NH2-induced scratching behavior, whereas histamine H1 receptor antagonist cetirizine or the cyclooxygenase inhibitor indomethacin had little effect. Furthermore, intradermal injection of SLIGRL-NH2 increased cutaneous levels of LTB4 and PGE2. In vitro, SLIGRL-NH2 treatment enhanced LTB4 and PGE2 release from primary keratinocytes in a concentration-dependent manner. Preincubation of keratinocytes with zileuton resulted in a significant decrease of LTB4 release and treatment of indomethacin led to a significant decrease of PGE2 in response to SLIGRL-NH2 stimulation. In addition, SLIGRL-NH2-induced secretion of LTB4 and PGE2 was significantly inhibited by tacrolimus, whereas cetirizine had no effect. These results indicate that SLIGRL-NH2 stimulates LTB4 and PGE2 release from mouse keratinocytes and that enhancement of LTB4 and PGE2 secretion contributes to SLIGRL-NH2-induced scratching behavior in ICR mice. [Copyright &y& Elsevier]

Abstract: Sodium ferulate (SF) loaded nanoparticles were prepared by desolvation procedure and subsequent cross-linking of the wall material of bovine serum albumin (BSA). Several factors in the nanoencapsulation process, such as the addition rate of the desolvation agent, composition of BSA and SF solution, amount of the cross-linker glutaraldehyde, were investigated to elucidate their influences on the particle size, zeta potential, drug loading and encapsulation efficiency of the resulted nanoparticles. The obtained spherical nanoparticles were negative charged with zeta potential from −20 to −40mV, and characterized between 100 and 200nm with a narrow size distribution. In the condition of introducing 1.0mL 8% glutareldehyde per mg of BSA, the drug entrapment efficiency (EE) of 80% (w/w) and loading capacity of about 16% (w/w) could be achieved for the cross-linked BSA nanoparticles with SF encapsulated (SF-BSA-NP). And the drug EE was decreased along with the increasing amount of glutareldehyde used for cross-linking. The in vitro drug release properties of SF-BSA-NP behaved with an initial burst effect and then sustained-release stage. To some extent, the drug release rate could be adjusted by cross-linking with different amount of glutaraldehyde. Compared with SF solution, SF-BSA-NP showed a much higher drug distribution into liver and a lower drug concentration in other tissues, after intravenously injected to mice. So, BSA based nanoparticles might be a suitable controlled released carrier for the freely water-soluble drug SF and further hepatic targeted drug delivery. [Copyright &y& Elsevier]