Chrysin Inhibitis Metabolic Inflammation Via Regulating Macrophage Polarization

Partâ…  Chrysin Inhibits Inflammation via Regulating Macrophage PolarizationMacrophages play a central role in inflammation and resisting the invasion of foreign microbes. Macrophages have high plasticity. They can exhibit different activation when accepting various stimulis in different environments. In inflammatory response, macrophages have three functions:antigen presentation, phagocytosis and immunomodulatory function via secretion of various cytokines and growth factors. Active molecules secreted by macrophage can participate in a beneficial inflammatory response and also participate in a harmful inflammatory response. Therefore, interfering macrophages and their secretion product can open a new way to control inflammatory diseases.Extensive literature studies have shown that flavonoids in the diet have anti-inflammatory and antioxidant role. Moreover, in recent years, many studies have shown that these flavonoids had a strong killing effect on tumor cells, indicating that the flavonoids can inhibit the tumor cells. In our study, we selected chrysin to study the macrophage activation regulation, and thus have a better understanding of the medicinal value of chrysin.Chrysin (5,7-di-OH-flavone), a widely distributed natural flavonoid, has been well documented for involving in various biological activities, especially in regulation of peroxisome proliferator activated receptor y (PPARy) activity as a modest modulator. However, the exact molecular mechanism is still unrevealed. In the current study, for the first time, we discovered that, chrysin not only significantly attenuated inflammation in high-fat feeding mice, but also alleviated high fat diet-induced hepatic, muscular steatosis in obese mice without altering the body weight. Chrysin decreases the infiltration of macrophages into adipose tissue in obese mice. In addition, chrysin was also found to induce an anti-inflammatory M2 phenotype and decreases M1 phenotype, both in peritoneal macrophages of obese mice and cultured macrophages in vitro, and thereby, chrysin changed the M1/M2 status. Our data further showed that chrysin regulated the phenotype of macrophages through enhancing the transcriptional activation of PPARy and the expression of its target genes. Taken together, we conclude that chrysin may serve as an effective modulator of PPARy during the pathogenesis of inflammation, thereby our findings shed light on the potential therapeutic feature of chrysin in recovering inflammatory diseases via regulating M1/M2 status.Partâ…¡ Breeding and Genotyping of Spontaneous Breast Cancer MiceThe MMTV-PyVT transgenic mouse is an animal model of spontaneous breast cancer. To lay foundation for studying the molecular mechanism of TAMs, we investigated the biological features of the transgenic mouse model and the pathological changes during its life span. All the breeders were raised in SPF conditions, and the results of mice breeding were recorded. Mast adenomas of MMTV-PyVT mice were observed by counting and measuring the tumors, and H&E staining for pathological development was conducted. MMTV-PyVT mice were well bred in our lab for that totally 128 offspring were obtained. The tumor biological features were obvious in MMTV-PyVT mice. Palpable mast adenoma occurred in about 8 weeks old and pulmonary metastasis occurred in the 3th week after the tumor occurred. Number and size of tumors increased as the mice grew up. The MMTV-PyVT transgenic mouse model was well kept and bred, and the occurring of breast tumors can be observed stably. This can be a typical animal model for breast carcinoma and TAM research.