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Colorectal cancer (CRC) is one of the most common cancers that threaten people in many countries. It is a multifactorial chronic disease caused by a combination of genetic and environmental factors, but it is mainly related to lifestyle, including diet. Plant-based foods and beverages are rich in polyphenols, which have antioxidant, anti-atherogenic, anti-inflammatory, and anti-cancer properties. These compounds are involved in host nutrition and disease pathogenesis in different ways. Polyphenolic compounds are used to prevent or inhibit cancer development and prognosis, examples include the green tea polyphenol (–) epigallocatechin-3-O-gallate (EGCG), curcumin, and resveratrol. Of course, there are more known and unknown polyphenolic compounds that need to be investigated for their anticancer properties. This article focuses on the role of polyphenols in the development, prevention, treatment, and prognosis of CRC by controlling gut inflammation, epigenetics, and gut microbiota.

Key words: polyphenols, colon cancer, intestinal inflammation, epigenetics, microbes
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Colorectal cancer (CRC) is one of the most common malignancies worldwide (1, 2). As with many diseases, CRC is caused by a variety of genetic and environmental factors (3). Globally, in 2018, CRC ranked third for all new cancer cases with more than 1.8 million new cases and second for deaths with more than 860,000 deaths (4). Although CRC has a genetic susceptibility syndrome, this disorder accounts for a small proportion of CRC cases (5). Based on analyzes of twin and family studies, the heritability of CRC is only 12-35%. The relatively low heritability of CRC reflects the importance of the environment, i.e., the environment plays a greater role in causing CRC from time to time (6). Cancer prevention is one of the public health priorities (7). Epidemiological studies of the relationship between diet and disease risk have shown that diet directly affects public health (8). In recent decades, considerable efforts have been made to evaluate the preventive chemical effects of natural products. Polyphenols have attracted much attention due to their advantages such as low side effects, wide availability, and low toxicity (9). Polyphenols are widely distributed in the plant world. They are believed to be useful in anti-inflammatory and anti-tumor drugs, which may be one of the good drugs for the prevention and treatment of cancer, and it affects the cancer disease process in many ways (10, 11). Therefore, polyphenols are considered as a potential source of molecules for the treatment of various cancers.

Health-related properties of polyphenols
Polyphenols are plant-derived phytochemicals that are abundant in tea, vegetables, soft fruits, and wine, and they regulate the stability of the gut microenvironment and reduce the risk of cancer (12-14). Although not explainable in the absence of symptoms, in vitro and animal model studies have shown polyphenols to have a wide range of pharmacological and therapeutic properties, including anticancer (13), anti-inflammatory (15), antioxidant (16), and vascular protection. properties (17). Epigallocatechin-3-gallate (EGCG) has been shown to inhibit melanoma cell growth by activating the 67 kDa laminin receptor (67LR) signaling pathway. Alternatively, 67LR is involved in the upregulation of EGCG-induced miRNA let-7b expression via cAMP/protein kinase A (PKA)/protein phosphatase 2A (PP2A) signaling, whereas let-7b downregulation leads to high-level downregulation. Mobility group A2 (HMGA2), a target gene associated with tumorigenesis (18). Olive oil polyphenols exhibit antioxidant and anti-inflammatory effects through a representative mixture of oxysterols, while Caco-2 is fully differentiated in intestinal epithelial-like cells. In addition, olive oil polyphenols can directly regulate the activation of NF-κB after the phosphorylation of p38 and JNK1/2, IκB phosphorylation, and inhibit the induction of iNOS, which can maintain the level of NO compared to the control group (19). Rich in polyphenols, plums prevent weight gain and increase serum high-density lipoprotein cholesterol and total cholesterol. In addition, it can reduce the levels of angiotensin II in blood plasma and its receptor Agtr1 in heart tissue, which suggests that polyphenols may be peroxisome proliferator-activated receptor-γ-agonists, and these results suggest that plums rich in polyphenols have the characteristic shows that myocardial protection (20). Studies have shown that chlorogenic acid activates IFN-γ mRNA expression and increases the number of IFN-γ+ CD4+ cells in mouse lymphoid aggregates, while decreasing the number of cells (IFN-γ+ CD4+, IFN-γ+ CD49b+, and IL-12+ in mouse spleen A significant increase in CD11b+ indicates that polyphenols have a specific stimulatory effect on the immune system of mice cells (21). Table 1 shows the health properties of various polyphenols from different sources. Diet and habits are closely related to the development of cancer. Studies have shown that green tea polyphenols have a protective effect in women with CRC, and there is a significant negative association between drinking 1 cup of tea per day and CRC risk (30). In addition, a study of the F344 rat model treated with n-azoxymethane showed that polyphenon E reduced tumor type and tumor size, decreased β-catenin nuclear expression, induced apoptosis, and increased RXRα, β, and γ expression levels in adenocarcinomas (26). ). Because of the low adverse effects and low toxicity of polyphenols, the biological activity of polyphenols has been a hot topic in many fields of research over the years (31).

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