Inhibitory Effect of Dietary Defatted Rice Bran in an AOM/DSS-Induced Colitis-Associated Colorectal Cancer Experimental Animal Model

Abstract

Defatted rice bran (DRB) is gaining immense popularity worldwide because of its nutritional and functional aspects. Emerging evidence suggests that DRB is a potential source of dietary fiber and phenolic compounds with numerous purported health benefits. However, less is known about its chemoprotective efficacy. In the present study, we determined and examined the nutrient composition of DRB and its chemopreventive effect on azoxymethane and dextran sulphate sodium (AOM/DSS)-induced colitis-associated colorectal cancer (CRC) in rats. The results showed the presence of several bioactive compounds, such as dietary fiber, phytic acid, and phenolic acids, in DRB. In addition, DRB supplementation reduced the progression of CRC symptoms, such as colonic shortening, disease activity index (DAI), and histopathological changes. Interestingly, a significant decrease was observed in total numbers of aberrant crypt foci (ACFs) and tumors with DRB supplementation. Furthermore, DRB supplementation suppressed the expression of pro-inflammatory cytokines (IL-6) and inflammatory mediators (NF-κB and COX-2) through the inactivation of the NF-κB signaling pathway. The administration of DRB revealed a negative effect on cancer cell proliferation by repressing the expression of nuclear β-catenin, cyclin D1, and c-Myc. These findings suggest that DRB supplementation mitigates chronic inflammation and cancer cell proliferation and delays tumorigenesis in rat AOM/DSS-induced colitis-associated CRC. Therefore, the establishment of DRB as a natural dietary food-derived chemopreventive agent has the potential to have a significant impact on cancer prevention in the global population.

Role of Dietary Defatted Rice Bran in the Modulation of Gut Microbiota in AOM/DSS-Induced Colitis-Associated Colorectal Cancer Rat Model

“…The increased production of SCFAs in the cecum of the induction + DRBL and induction + DRBH groups was correlated with the increase in the SCFAs-producing bacteria, including Ruminococcus , Butyricicoccus , and Roseburia , respectively. Furthermore, the increased SCFA production in the induction + DRBL and induction + DRBH groups was related to the decrease in pro-inflammatory markers, including TNF-α, IL-6, NF-κB, and COX-2, together with the reduction in the number of aberrant crypt foci (ACFs), and tumor formation in the colon in our previous study [ 26 ]. This is in line with the previous study that showed enzyme-treated rice fiber increased SCFAs (acetate, propionate, and butyrate) contents in the cecum and reduced inflammatory cytokines (TNF-α, IL-4, IFN-γ, IL-1β, IL-6, and IL-12p70) in serum and mucosal in DSS-induced rat [ 52 ].…”

“…Our previous investigations demonstrated that DRB have a substantial amount of dietary fiber [ 26 ]. The degradation and fermentation of these dietary fibers by bacterial enzymes produce short-chain fatty acids (SCFAs), which serve as an energy source for colonocytes and maintain intestinal homeostasis [ 27 ].…”

“…In addition, in our previous study, we determined that DRB has high phenolic acids, which also contribute to intestinal bacteria [ 26 ]. These compounds have the property to promote the growth of Bidifobacteria , such as Faecalibacterium prausnitzii , Lactobacillus sp., and Akkermansia muciniphila , respectively [ 46 ].…”

Integrated Microbiota and Metabolite Changes following Rice Bran Intake during Murine Inflammatory Colitis-Associated Colon Cancer and in Colorectal Cancer Survivors

“…Rice bran CRC protective phytochemicals induce apoptosis and block cell proliferation to prevent tumor growth [ 25 , 26 , 27 ]. Numerous studies have previously documented the CRC prevention properties associated with brown rice and rice bran [ 13 , 14 , 16 , 17 , 28 , 29 , 30 ]. The bioactive metabolites from rice bran reduce inflammation by scavenging free radicals [ 31 ] and triggering anti-tumor immune responses in the colonic microenvironment [ 32 , 33 , 34 ].…”

“…Though there are well-established studies in the literature documenting rice bran’s role in CRC control and prevention [ 13 , 14 , 16 , 17 , 28 , 29 , 30 ], a gap in knowledge exists for the time-dependent, weekly changes to fecal microbial communities and metabolites associated with the host digestion of rice bran, which are directly and indirectly contributing to reducing CRC formation. In this regard, we recently reported how rice bran intake results in less local and systemic inflammation in the colon tissue and plasma in an AOM-DSS pre-clinical murine model [ 17 ].…”