Effects And Mechanisms Of Propolis On Inflammatory Diseases And Inflammatory Microenvironment

Inflammation is an integral physiological host response to tissue injury and infection, which is vital for our body when facing invading microbes/pathogens. Inflammation influences the microenvironments of the body and interacts with various kinds of cells and mediators. It also participated in various physiological and pathological processes. Despite the fact that inflammation itself did not caused serious complicated diseases (like cancer), it plays important roles during the disease development and the disease progression. Propolis is a resinous substance collected by honeybees, Apis mellifera, from various plant sources. It has been used in folk medicines and complementary therapies since ancient times with various pharmacological and biological activities. The anti-inflammatory activity of propolis has been well documented. Based on our previous studies, this study using in vitro and in vivo inflammatory modes and investigated the effects of propolis on inflammatory diseases (LPS induced mice acute lung injury model and DSS induced rats colitis model) and on inflammatory microenvironment (intestinal microenvironment and immune microenvironment). The main research findings are summarized as follows:1. Effects of Chinese poplar type propolis extracts and its botanic origin poplar buds extracts on LPS induced mice acute lung injuryThe main botanic phytochemical constitutes of Chinese poplar propolis and poplar buds are quite similar but quantity analysis results showed that Chinese poplar propolis has more abundant polyphenolic compounds than poplar buds, together with stronger in vitro free radical scavenging activities. In LPS challenged mice, we noticed that both Chinese poplar propolis and poplar buds administration to the mice (100mg/kg) inhibited serum inflammatory cytokines production (IL-6, MCP-1, TNF-a and IL-12p70), and alleviated inflammatory responses in the lungs.2. Effects of Chinese propolis on DSS induced colitis in ratsDSS solutions (3%) were made in the drinking water to induce ulcerative colitis model using SD rats. We found that dietary supplement of propolis (0.1%,0.2% and 0.3%) showed distinct protective effects against DSS induced colitis. Dietary supplement of 0.3% propolis showed best effects by decreasing disease activities index, alleviated pathological changes in rats’colon and decreasing cecum SCFA.3. Effects and mechanisms of Chinese propolis on the barrier function of Caco-2 intestinal epithelial cellsChinese propolis significantly increased TER of Caco-2 monolayers and decreased lucifer yellow permeability. Propolis treatment significantly increased TJ protein ZO-1 and occludin mRNA expressions. Western blot results showed that Chinese propolis activated AMPK-α, AKT, ERK1/2 and p38. Using selective inhibitors we found that the regulating effects by Chinese propolis was dependent on the activation of AMPK-a and ERK1/2 but negatively regulated by the activation of p38.4. Effects and mechanisms of Chinese propolis and Brazilian propolis on the immune regulation of macrophagesIn vitro macrophage inflammation models were used to explore the regulating effects and mechanisms of propolis in the inflammatory microenvironment. Despite of the chemical differences between Chinese and Brazilian propolis, they showed distinct anti-inflammatory effects by inhibiting LPS stimulated inflammatory cytokines production and alleviated cellular ROS accumulation. Reporter assays showed that propolis significant demolished NF-κB activation, but their modulating mechanisms are different. Brazilian propolis inhibited IκB-α phosphorylation and degradation in LPS stimulated macrophages. Chinese propolis inhibited IκB-α phosphorylation but showed no results on its degradation. We further established a HeLa-T6RZC cell line and demonstrated that propolis suppressed NF-κB activities by inhibiting the E3 activity of TRAF6 and controlling its auto-ubiquitination.Taken together, this study used models of inflammatory diseases in animals and inflammatory microenvironment in cells to explore the anti-inflammatory effects/mechanisms of propolis. These data suggest that propolis extracts may be useful as an alternative/additive therapeutic strategy against inflammation diseases and for complex diseases like cancer, cardiovascular diseases and diabetes.