Inhibitory effects of black tea theaflavin derivatives on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and arachidonic acid metabolism in mouse ears

Tea has been shown to possess several health beneficial properties primarily due to its polyphenolic content. The major polyphenolic compounds in black tea leaves are theaflavins (TFs) formed by oxidative coupling of catechins in tea leaves during its processing. In this paper, we report the characterization of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear inflammatory model and the inhibitory effects of major black tea TFs derivatives on this inflammation. In addition, the effect on inflammatory biomarkers, such as proinflammatory cytokines and arachidonic acid metabolites, are reported as well. A single topical application of TPA to ears of CD-1 mice induced a time- and dose-dependent increase in edema as well as formation of proinflammatory cytokine proteins interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in mouse ears. A single topical application of equimolar of black tea constituents (TF, theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate) strongly inhibited TPA-induced edema of mouse ears. Application of TFs mixture to mouse ears 20 min prior to each TPA application once a day for 4 days inhibited TPA-induced persistent inflammation, as well as TPA-induced increase in IL-1beta and IL-6 protein levels. TFs also inhibited arachidonic acid (AA) metabolism via both cyclooxygenase (COX) and lipoxygenase pathways. This observation was substantiated by decreased amounts of AA metabolites prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. Combined application of TF and sulindac, a nonsteroidal anti-inflammatory drug resulted a significant synergetic anti-inflammatory effect. Oral administration of TFs or the hot water extract of black tea leaves also significantly inhibited TPA-induced edema in mouse ears. In conclusion, proinflammatory cytokines, IL-1beta and IL-6, as well as the intermediated metabolites of AA, PGE2, and LTB4 are good biomarkers for inflammation. Black tea constituents, TF and its derivatives, had strongly anti-inflammatory activity in vivo which may be due to their ability to inhibit AA metabolism via lipoxygenase and COX pathways.     

Chemopreventive effect of dietary curcumin on inflammation‐induced colorectal carcinogenesis in mice

Scope: Curcumin is a polyphenol with a variety of pharmacologic effects. We evaluate the effect of dietary curcumin on the severity of repeated colitis‐associated colorectal cancer. Methods and results: Six‐week‐old C57BL/6 mice were randomized into two dietary groups: standard diet and curcumin at 0.6% diet. The mice were exposed to 15 cycles of 0.7% dextran sodium sulphate for 1 week followed by distilled water for 10 days. After curcumin diet, the disease activity index presented a statistical reduction in the last cycles, macroscopic tumors were not seen and the microscopic study showed minor neoplasic lesions with respect to standard diet‐group. β‐Catenin translocation to the cytoplasm and/or nucleus was observed in the tumor tissue, but this translocation and its intensity were significantly minor in the curcumin diet‐DSS animals. Cytokines as tumor necrosis factor‐α and IFN‐γ were significantly diminished in DSS‐animals fed with curcumin. Conversely, non‐modification of p53 expression was observed and cyclo‐oxygenase‐2 and inducible nitric oxide synthase were significantly reduced in the curcumin diet‐DSS group. Conclusion: We demonstrate the protective/preventive effect of curcumin in the progression of colorectal cancer associated to colitis, which was correlated with a lowered immunoreactivity of ß‐catenin, a non‐modification of p53 expression, a reduction of proinflammatory cytokine levels and a decrease of inflammatory protein overexpression.