The transcriptional factors nuclear factor-κB (NF-κB) and NF-E2-related factor 2 (Nrf2) have been recently reported to have critical roles in protecting various tissues against inflammation and colitis-associated colorectal cancer (aberrant crypt foci). Our previous studies showed that wogonin (5,7-dihydroxy-8-methoxyflavone) possessed anti-neoplastic and anti-inflammatory activities. The present study extended these important earlier findings by exploring the effect of wogonin on the initiation and development of colitis-associated cancer. Wogonin lowered tumor incidence and inhibited the development of colorectal adenomas in azoxymethane- or dextran sulfate sodium-induced mice. We found that wogonin significantly decreased the secretion and expression of IL-6 and IL-1β, reduced cell proliferation and nuclear expression of NF-κB in adenomas and surrounding tissues and promoted Nrf2 nuclear translocation in surrounding tissues, although overexpressed Nrf2 in tumor tissues was independent of wogonin administration. Furthermore, wogonin inhibited the interaction between human monocytic THP-1 cells and human colon cancer HCT116 cells, and significantly downregulated lipopolysaccharide-induced secretion of prototypical pro-inflammatory cytokines IL-6 and IL-1β in THP-1 cells. Further mechanism research revealed that wogonin inhibited the nuclear translocation of NF-κB and phosphorylation of IκB and IKKα/β, and promoted Nrf2 signaling pathway in HCT116 cells and THP-1 cells. Taken together, the present results indicated that wogonin effectively suppressed inflammation-associated colon carcinogenesis and cancer development, suggesting its potential as a chemopreventive agent against colitis-associated colon cancer.

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Background : Cerebral ischemia-reperfusion (I/R) injury as a serious threat to human health is characterized by cerebral endothelial leakage, as a result of the damage of blood-brain barrier (BBB). It is thus quite attractive to realize real-time monitoring of BBB damage for therapeutic surveillance.Methods : In this study, a radioactive probe is constructed by conjugating ruscogenin (Rus), a neuroprotectants, to technetium-99m (Tc 99m ) to assess the damage of cerebral endothelial in BBB.Results : In vitro study proves that the probe can penetrate more efficiently in damaged BBB. Then, longitudinal nuclear imaging distinguishes mice with BBB leakage from normal ones, which is validated by evans blue staining of brain tissue. Higher nuclear signal also correlates with poorer blood circulation in brain. Further, by visualizing brain signal during drug treatment, the probe finds that the most obvious protective efficacy of Rus occurs at 12 h post administration, which is superior than edaravone (Edara).Conclusion : Altogether, the probe is promising to monitor I/R injury real-time by radioactive-imaging of BBB integrity. Importantly, Rus as a neuroprotectants may serve as a potential theranostic agent for I/R treatment.

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