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Colorectal cancer (CRC) is one of the most common cancer worldwide. Chronic inflammation contributes to CRC development and progression. Emodin, is a natural anthraquinone derivative with anti-oxidant, anti-inflammatory, and anti-tumor activities. We used the AOM/DSS model of colitis-associated intestinal tumorigenesis to characterize the effect of Emodin on inflammation and tumorigenesis at weeks 3, 5, and 14 after initiation with AOM. At all three time points, Emodin (50 mg/kg) reduced inflammatory cell (i.e. CD11b+ and F4/80+) recruitment, cytokine (i.e. TNFα, IL1α/β, IL6, CCL2, CXCL5) and pro-inflammatory enzymes (i.e. COX-2, NOS2) expression in the tumor microenvironment, while promoting recruitment of CD3+ T lymphocytes at 14 weeks. Emodin decreased the incidence of premalignant lesions (adenoma) at week 3, the incidence of dysplastic lesions and carcinomas at week 5, and the incidence, size and the invasiveness of carcinomas at week 14. Emodin also reduced the acute clinical intestinal symptoms (i.e. bleeding and diarrhea) during DSS treatment. In vitro, Emodin inhibited the expression of pro-inflammatory mediators by LPS-stimulated RAW 264.7 macrophages, and reduced viability, adhesion, migration, and fibroblasts-induced invasion of SW620 and HCT116 colon cancer cells. In conclusion, this work demonstrates that Emodin suppresses carcinogenesis-associated intestinal inflammation and prevents AOM/DSS-induced intestinal tumorigenesis and progression. These results instigate further studies on Emodin as a natural agent for the prevention or treatment of colorectal cancer.

The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic triterpenes of glycine structure according to 1H-NMR and 13C-NMR spectra, which is β-elemonic acid (β-EA). We determined the content of six different localities of frankincense; the average content of β-EA was 41.96 mg/g. The toxic effects of β-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the β-EA groups showed no systematic variations. The anti-inflammatory effects of β-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. β-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with β-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with β-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (p < 0.01). In conclusion, our study indicates that β-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.

Cyclooxygenase (COX)-2 is increased in human chronic pancreatitis. We recently demonstrated in a model of chronic pancreatitis (WBN/Kob rat) that inhibition of COX-2 activity reduces and delays pancreatic inflammation and fibrosis. Monocyte chemoattractant protein (MCP)-1 mRNA and PGE2 were significantly reduced, correlating with a decreased infiltration of macrophages. MCP-l plays an important role in the recruitment of macrophages to the site of tissue injury. The aim of our study is to identify mechanisms by which macrophages and acinar cells maintain an inflammatory reaction. The expression profile of E prostanoid receptors EP1-4 and MCP-1 was analyzed by RT-PCR from pancreatic specimens and AR42J cells. MCP-l secretion was detected by ELISA from rat pancreatic lobuli. We determined EP1-4 mRNA levels in WBN/Kob rats with chronic pancreatic inflammation. Individual isoforms were highly increased in rat pancreas, concurrent with MCP-1 mRNA expression. In supernatants of pancreatic lobuli and AR42J cells, MCP-1 was detectable by ELISA. In the presence of TNF-α, MCP-1 was upregulated. Coincubation with PGE2 enhanced the TNF-α-induced MCP-1 synthesis significantly. Similarly, TNF-α mRNA was synergistically upregulated by TNF-α and PGE2. Furthermore, the synergistic effect of TNF-α and PGE2 was abolished by inhibition of PKA but not of PKC. We conclude that EP receptors are upregulated during chronic pancreatic inflammation. PGE2 modulates the TNF-α-induced MCP-1 synthesis and secretion from acinar cells. This synergistic effect is controlled by PKA. This mechanism might explain the COX-2- dependent propagation of pancreatic inflammation. [ABSTRACT FROM AUTHOR]