Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders.

The pathogenesis of sepsis is characterized by overwhelming inflammatory responses that lead to tissue damage and organ failure. Toll-like receptor (TLR) signaling is crucial for induction of hyperinflammatory responses and tissue injury during sepsis. Genipin, an aglycon of geniposide, has antiinflammatory and antimicrobial activities. The purpose of this study was to test the hypothesis that genipin reduces multiple organ dysfunction and mortality during sepsis through inhibition of TLR signaling. Male ICR were subjected to sepsis by cecal ligation and puncture (CLP) or endotoxemia by lipopolysaccharide (LPS). Various doses of genipin (1, 2.5 and 5 mg/kg) or a vehicle were administered intravenously immediately after CLP or intraperitoneally after LPS treatment. In another set of survival tests, mice were treated with 2.5 mg/kg of genipin 0 and 24 h after CLP. Genipin was found to improve survival and to attenuate multiple organ dysfunction. Genipin attenuated production of proinflammatory cytokines and release of high-mobility group box 1 (HMGB1). Genipin prevented TLR2 and TLR4, myeloid differentiation factor 88 and the Toll/interleukin-1 receptor domain-containing adaptor protein, inducing interferon-β overexpression. Phosphorylation of mitogen-activated protein kinases and interferon regulatory factor 3 and translocation of nuclear factor (NF)-κB were prevented by genipin. Moreover, genipin attenuated increases in serum tumor necrosis factor-α and HMGB1 in LPS-induced endotoxemia. Pam3CSK4- and LPS-mediated production of nitrites and proinflammatory cytokines was suppressed by genipin in RAW264.7 cells. Genipin attenuated mortality and organ injuries during sepsis through interference with TLR signaling. Therefore, genipin might be useful as a potential therapeutic agent for treatment of sepsis.

This study was conducted to develop a construct model regarding the daily activities, emotional security provided by food, enjoyment of food, level of satisfaction with delivered food, and the quality of life of homebound seniors who benefitted from meal delivery programs. The data were analyzed by SAS 9.2 and the Structural Equation Model (SEM), which was created by Analysis of Moment Structure (AMOS) 5.0 packages. The reliability of the data was confirmed by an exploratory factor analysis and through a Cronbach's alpha coefficient, and the measurement model proved to be appropriate by a confirmatory factor analysis of the measurement model in conjunction with AMOS. The results of the correlations between all the variables showed significant positive correlations (P < 0.05). The path analysis demonstrated that the daily activities (P < 0.01) and the emotional security created by food (P < 0.05) had positive correlations with the foodservice satisfaction (P < 0.05), while the daily activities (P < 0.05), the sense of emotional security made by food (P < 0.05), and food enjoyment (P < 0.05) also presented significant positive correlations with the quality of life. However, the food service satisfaction was shown to directly, but not significantly, affect the quality of life. This revealed that the current meal delivery programs needed to be improved in several directions.

This study evaluated the potential beneficial effect of Moutan Cortex Radicis (MCR) in a murine model of carbon tetrachloride (CCl4)-, D-galactosamine (GalN)- and α-naphthylisothiocyanate (ANIT)-induced liver injury. Acute hepatotoxicity was induced by intraperitoneal injection of CCl4 (10 µL/kg), GalN (700 mg/kg), and ANIT (40 mg/kg). Animals received MCR (30, 100, and 300 mg/kg ) orally at 48, 24, and 2 h before and 6 h after administration of CCl4, GalN, and ANIT. Serum activities of aminotransferase were significantly higher at 24 h after CCl4 or GalN treatment. These changes were attenuated by MCR. Histopathological analysis revealed multiple and extensive areas of portal inflammation, hepatocellular necrosis, and an increase in inflammatory cell infiltration. These changes were inhibited by MCR. Serum total bilirubin concentration increased and bile flow decreased significantly 48 h after ANIT treatment, which was attenuated by MCR. Our results suggest that MCR has a protective effect on acute liver injury.

Therapeutic effects of GCSB-5 on osteoarthritis were measured by the amount of glycosaminoglycan in rabbit articular cartilage explants in vitro, in experimental osteoarthritis induced by intra-articular injection of monoiodoacetate in rats in vivo. GCSB-5 was orally administered for 28 days. In vitro, GCSB-5 inhibited proteoglycan degradation. GCSB-5 significantly suppressed the histological changes in monoiodoacetate-induced osteoarthritis. Matrix metalloproteinase (MMP) activity, as well as, the levels of serum tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase protein, and mRNA expressions were attenuated by GCSB-5, whereas the level of interleukin-10 was potentiated. By GCSB-5, the level of nuclear factor-κB p65 protein expression was significantly attenuated but, on the other hand, the level of inhibitor of κB-α protein expression was increased. These results indicate that GCSB-5 is a potential therapeutic agent for the protection of articular cartilage against progression of osteoarthritis through inhibition of MMPs activity, inflammatory mediators, and NF-κB activation.

We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) has immunostimulatory effects including macrophage activation. Analysis of infiltration of inflammatory cells into peritoneal cavity showed GDB treatment significantly increased the recruitment of macrophages, lymphocytes, neutrophils, and monocytes into the peritoneal cavity. Treatment of spleen cells isolated from C57BL/6 mice with GDB significantly increased the proliferation of B cells and T cells induced by LPS and ConA, respectively. Treatment with GDB significantly increased the cytolytic capacity of NK cells and macrophages against YAC-1 and B16 cells, respectively. In order to further confirm and investigate the mechanism of GDB on macrophage activation, we analyzed the effects of GDB on the cytokine expression including iNOS, IL-1β, and TNF-α in mouse macrophage cell line, RAW 264.7 cells. RT-PCR and ELISA showed that GDB increased the expression of IL-1β, and TNF-α, whereas iNOS was not induced by GDB. Collectively, this series of experiments indicates that GDB stimulates immune system including macrophage activation.