5-Demethylnobiletin is more effective than nobiletin in preventing AOM/DSS-induced colorectal carcinogenesis in ICR mice

Abstract

Nobiletin and 5-demethylnobiletin as polymethoxyflavone and hydroxy polymethoxyflavone, especially, have been reported to exhibit various beneficial biological activities for human health. In this study, the effects of NOB and 5-demethylnobiletin (DMNB), on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal carcinogenesis in Institute for Cancer Research (ICR) mice were compared. We found that NOB and DMNB significantly alleviated the weight loss, colon length and reduced colon tumor formation in AOM/DSS-induced colorectal carcinogenesis mice. At the molecular level, our results from western blot and polymerase chain reaction (PCR) analysis showed that 0.025% of NOB and DMNB presented an anti-inflammation property by reducing cyclooxygenase- 2 (COX-2) and interleukin 6 (IL-6) expression. Taken together, these results demonstrate that DMNB had a better chemo-preventive efficacy than NOB in AOM/DSS-induced colorectal carcinogenesis in ICR mice model.

Regulation of Xenobiotic-Metabolizing Enzymes by 5-Demethylnobiletin and Nobiletin to Mitigate Benzo[a]pyrene-Induced DNA Damage In Vitro and In Vivo

“…Control cells were treated with DMSO to yield a final concentration of 0.5%. The amounts of 5-DMNB, NBT, and B­[a]P used were based on previous studies. , The cells were seeded at a density of 2 × 10 5 cells/mL in 96-well plates and incubated for 12 h before being cotreated with B­[a]P (20 μM) with or without 5-DMNB or NBT (2.5 or 10 μM). After 72 h of incubation, cell viability was evaluated using the classical methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay.…”

“…9 Verified research has shown that 5-DMNB is more effective than NBT in preventing colorectal carcinogenesis induced by azoxymethane/DSS. 22 However, the full extent of the effects of NBT and 5-DMNB on B[a]P metabolism in the colon has not been fully elucidated. Therefore, we aimed to assess the protective effects of 5-DMNB and NBT on mediating the biotransformation of B[a]P using both in vitro and in vivo experiments.…”

“…Our previous studies have also shown that PMFs extracted from citrus peels can reduce the incidence of B­[a]­P/DSS-induced polyps . Verified research has shown that 5-DMNB is more effective than NBT in preventing colorectal carcinogenesis induced by azoxymethane/DSS . However, the full extent of the effects of NBT and 5-DMNB on B­[a]P metabolism in the colon has not been fully elucidated.…”

Anthocyanins and intestinal barrier function: a review

“…Intestinal barrier dysfunction is common in IBD and a central mechanism by which dietary bioactives may mitigate colitis. Polyphenols are promising bioactives to improve intestinal barrier function and prevent colitis (Murphy et al, 2018;Wu et al, 2018). However, berry anthocyanins are extensively metabolized by host tissue and gut microbiota.…”

“…However, berry anthocyanins are extensively metabolized by host tissue and gut microbiota. These catabolites also have variable absorption and intrinsic anti-inflammatory activity (Wang et al, 2018;Wu et al, 2018). Therefore, the objectives of this review are to describe the essential components of intestinal barrier function in the context of chronic inflammation and to elaborate the means by which berry anthocyanins and its known catabolites could inhibit IBD by improving intestinal barrier function.…”