Colonic inflammation induces local glucocorticoid activation via 11betaHSD1 and impairs glucocorticoid inactivation via 11betaHSD2. The observed changes indicate a role for local metabolism of glucocorticoids in the control of colonic inflammation.
Glucocorticoids are considered to synchronize the rhythmicity of clock genes in peripheral tissues; however, the role of circadian variations of endogenous glucocorticoids is not well defined. In the present study, we examined whether peripheral circadian clocks were impaired by adrenalectomy. To achieve this, we tested the circadian rhythmicity of core clock genes (Bmal1, Per1-3, Cry1, RevErbα, Rora), clock-output genes (Dbp, E4bp4) and a glucocorticoid- and clock-controlled gene (Gilz) in liver, jejunum, kidney cortex, splenocytes and visceral adipose tissue (VAT). Adrenalectomy did not affect the phase of clock gene rhythms but distinctly modulated clock gene mRNA levels, and this effect was partially tissue-dependent. Adrenalectomy had a significant inhibitory effect on the level of Per1 mRNA in VAT, liver and jejunum, but not in kidney and splenocytes. Similarly, adrenalectomy down-regulated mRNA levels of Per2 in splenocytes and VAT, Per3 in jejunum, RevErbα in VAT and Dbp in VAT, kidney and splenocytes, whereas the mRNA amounts of Per1 and Per2 in kidney and Per3 in VAT and splenocytes were up-regulated. On the other hand, adrenalectomy had minimal effects on Rora and E4bp4 mRNAs. Adrenalectomy also resulted in decreased level of Gilz mRNA but did not alter the phase of its diurnal rhythm. Collectively, these findings suggest that adrenalectomy alters the mRNA levels of core clock genes and clock-output genes in peripheral organs and may cause tissue-specific modulations of their circadian profiles, which are reflected in changes of the amplitudes but not phases. Thus, the circulating corticosteroids are necessary for maintaining the high-amplitude rhythmicity of the peripheral clocks in a tissue-specific manner.
In recent years, interest in hop-derived constituents, especially for prenylflavonoids has grown, as they have a wide range of biological properties including antioxidant, anticarcinogenic and antimicrobial activities. Two main hop prenylflavonoids, xanthohumol and isoxanthohumol, and hop extract enriched in prenylflavonoids, were tested for their antiproliferative activities on colon cancer cell lines, HT-29 and SW620, and a noncancerous cell line, IEC-6. It was confirmed that both xanthohumol and isoxanthohumol inhibited cell proliferation, even at micromolar concentrations. For cell line HT-29, the IC 50 was 1.2 ± 0.9 and 16.9 ± 0.9 μmol dm À3 for xanthohumol and isoxanthohumol, respectively. Similar values were obtained for SW620 cells (2.5 ± 0.2 and 37.3 ± 3.2 μmol dm -3 ). None of the pure prenylflavonoids that were tested affected the proliferation of the noncancerous cell line, IEC-6. The effect of the hop extract containing xanthohumol was also tested for antiproliferative activities on the cancer cell lines, HT-29 (IC 50 = 3.1 ± 0.2 μmol dm -3 ) and SW620 (IC 50 = 1 ± 0.2 μmol dm À3 ), and on the cell line, IEC-6 (IC 50 = 65.5 ± 11.3 μmol dm À3 ). The results showed a similar trend to that for pure compounds, suggesting a possible future application of hop extracts in the pharmaceutical industry.
Conjugated linoleic acids (CLA) are distinctive polyunsaturated fatty acids. They are present in food produced by ruminant animals and they are accumulated in seeds of certain plants. These naturally occurring substances have demonstrated to have anti-carcinogenic activity. Their potential effect to inhibit cancer has been shown in vivo and in vitro studies. In this review, we present the multiple effects of CLA isomers on cancer development such as anti-tumor efficiency, anti-mutagenic and anti-oxidant activity. Although the majority of the studies in vivo and in vitro summarized in this review have demonstrated beneficial effects of CLA on the proliferation and apoptosis of tumor cells, further experimental work is needed to estimate the true value of CLA as a real anti-cancer agent.
Colitis induces local glucocorticoid activation from 11-oxo steroids and decreases glucocorticoid inactivation; i.e. inflammation increases local tissue ratio of active and inactive glucocorticoids. The results indicate that the changes in local metabolism of glucocorticoids could contribute to the control of an overshoot of inflammation processes in the colon.
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