Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) through down-regulation of NF-κB translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of TNF-α and reduced the protein and mRNA expression of TNF-α in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of TNF-α and the expressions of scavenger receptors.

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-1β, IL-6, TNF-α, 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-κB, 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-κB-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.

Inflammation is increasingly regarded as a key process underlying metabolic diseases in obese individuals where obese adipose tissue shows features characteristic of active local inflammation. Metformin is a biguanide derivative used in the treatment of T2D and one of the world's most widely prescribed drugs and have been suggested that metformin has anti-inflammatory properties. Here we show that metformin efficiently attenuates the metabolic disorder in DIO mice and suppresses MHC-restricted antigen presentation in dendritic cells. This study was to investigate the therapeutic effect of metformin on diabetic symptoms in DIO mice. Metformin decreased aipogenesis related gene, FAS, SCD-1, GPAT, SREBP1a, but also suppressed gene expression of innate cytokines than control mice. Metformin decreased both class I- and class II-restricted presentation of exogenous OVA in dendritic cells. Metformin also decreased expression of the co-stimulatory molecules, ICAM-1 and B7-1/-2, and MHC class I and II molecules but not phagocytic activity of DCs. Metformin decreased MHC class II-restricted exogenous antigen presentation in peritoneal macrophages in vivo. These results show that metformin attenuates immune responses followed by decreases MHC-restricted presentation of exogenous antigen in DCs via intracellular processing events. Theses finding suggest that modulation of the antigen presentation pathway could provide a novel means for regulating T cell responses in metabolic diseases.

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