Immunomodulatory Effects of Dioscoreae Rhizome Against Inflammation through Suppressed Production of Cytokines Via Inhibition of the NF-kappaB Pathway

Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, and PGE2, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-kappaB, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-kappaB-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.

Dietary Aloe QDM Complex Reduces Obesity-Induced Insulin Resistance and Adipogenesis in Obese Mice Fed a High-Fat Diet

Obesity-induced disorders contribute to the development of metabolic diseases such as insulin resistance, fatty liver diseases, and type 2 diabetes (T2D). In this study, we evaluated whether the Aloe QDM complex could improve metabolic disorders related to blood glucose levels and insulin resistance. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of Aloe QDM complex or pioglitazone (PGZ) or metformin (Met) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Dietary Aloe QDM complex lowered body weight, fasting blood glucose, plasma insulin, and leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Also, Aloe QDM complex significantly enhanced plasma adiponectin levels and insulin sensitivity via AMPK activity in muscles. At the same time, Aloe QDM decreased the mRNA and protein of PPARgamma/LXRalpha and scavenger receptors in white adipose tissue (WAT). Dietary Aloe QDM complex reduces obesity-induced glucose tolerance not only by suppressing PPARgamma/LXRalpha but also by enhancing AMPK activity in the WAT and muscles, both of which are important peripheral tissues affecting insulin resistance. The Aloe QDM complex could be used as a nutritional intervention against T2D.

Role of Salvia miltiorrhiza for Modulation of Th2-derived Cytokines in the Resolution of Inflammation

BACKGROUND: Salvia miltiorrhiza (SM) has been used to treat inflammatory diseases including edema and arthritis; however, the anti-inflammatory mechanism of SM action remains unresolved. METHODS: The effects of an ethanol extract of SM (ESM) on pro-inflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, and NO, on anti-inflammatory cytokines including IL-4, IL-10, TGF-beta, and IL-1Ra have been studied in an attempt to elucidate the anti-inflammatory mechanism in murine macrophages. RESULTS: ESM inhibited the production of pro-inflammatory cytokines via down-regulation of gene and protein expression whereas it increased the anti-inflammatory cytokines. Furthermore, ESM inhibited the expression of the chemokines, RANTES and CX3CL1, as well as of inflammatory mediators such as TLR-4 and 11beta-HSD1. CONCLUSION: These results indicated that the regulatory effects of ESM may be mediated though the suppression of pro-inflammatory cytokines as well as the induction of anti-inflammatory cytokines. Consequently, we speculate that ESM has therapeutic potential for inflammation-associated disorders.

Role of Salvia miltiorrhiza for Modulation of Th2-derived Cytokines in the Resolution of Inflammation

BACKGROUND: Salvia miltiorrhiza (SM) has been used to treat inflammatory diseases including edema and arthritis; however, the anti-inflammatory mechanism of SM action remains unresolved. METHODS: The effects of an ethanol extract of SM (ESM) on pro-inflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, and NO, on anti-inflammatory cytokines including IL-4, IL-10, TGF-beta, and IL-1Ra have been studied in an attempt to elucidate the anti-inflammatory mechanism in murine macrophages. RESULTS: ESM inhibited the production of pro-inflammatory cytokines via down-regulation of gene and protein expression whereas it increased the anti-inflammatory cytokines. Furthermore, ESM inhibited the expression of the chemokines, RANTES and CX3CL1, as well as of inflammatory mediators such as TLR-4 and 11beta-HSD1. CONCLUSION: These results indicated that the regulatory effects of ESM may be mediated though the suppression of pro-inflammatory cytokines as well as the induction of anti-inflammatory cytokines. Consequently, we speculate that ESM has therapeutic potential for inflammation-associated disorders.

Cordyceps militaris Enhances MHC-restricted Antigen Presentation via the Induced Expression of MHC Molecules and Production of Cytokines

BACKGROUND: Cordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs). METHODS: Dendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis. RESULTS: CME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot. CONCLUSION: These results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs.