Effects of hibisco (Hibiscus sabdariffa L.) intake on the development of preneoplastic lesions ando n the composition of the intestinal microbiota of Balb/c mice
Authors:   , Bernardes Andressa Ladeira 
Published: June 2023

Colorectal câncer (CRC) includes morphological and pathological changes that affect the entire colon and rectum segment, with the appearance of aberrant crypt foci (ACF). ACFs are considered the first pre-neoplastic lesions that can progress to CRC. In addition to genetic factors, the development of CRC is also influenced by modifiable factors, that is, factors related to the individual's lifestyle. Therefore, changes related to lifestyle, such as the consumption of a diet rich in bioactive compounds, fibers, among others, contribute to reducing the risk of developing pre-neoplastic lesions and, consequently, CRC. Hibiscus sabdariffa L. is a medicinal plant belonging to the Malvaceae family, a source of bioactive compounds such as phenolic compounds, anthocyanins and dietary fiber. These compounds have antioxidant, anti-inflammatory, anti-proliferative properties, in addition to being hepatoprotective. Another possible mechanism of action of phenolic compounds in the body refers to the modulation of the intestinal microbiota, being metabolized by colonic bacteria producing metabolites and serving as a substrate for bacterial growth. In view of the above, the objective of the present study was to investigate whether the supplementation of 5% and 10% of dehydrated calyces of H. sabdariffa (DHSC) have the ability to attenuate the development of pre-neoplastic lesions, in addition to acting as prebiotics modulating the composition of the intestinal microbiota of mice. An in vivo experiment was carried out for 12 weeks, the animals were randomly divided into 3 experimental groups: the control group and the groups supplemented with 5% DHSC and 10% DHSC. During the first 8 weeks, the animals were induced to pre-neoplastic lesions with injection of the drug 1,2-Dimetilhidrazine (DMH). Manuscript 1: characterization of DHSC, determination of the activities of hepatic catalase and superoxide dismutase enzymes, ACF count, quantification of short-chain fatty acids, count of inflammatory infiltrates, goblet cells and leukocytes in the colonic mucosa. There was a significant reduction in ACF and in the presence of inflammatory infiltrates in the colon of animals in the 5DHSC and 10DHSC groups. The 10DHSC group showed an increase in the activity of the catalase enzyme, in the production of butyrate and in the presence of NK cells in the colon, in addition to more hypertrophied goblet cells. Based on these findings, it is suggested that DHSC supplementation may be recommended to attenuate cellular responses in the early stage of pre-neoplastic lesions. Manuscript 2: A systematic review was performed to elucidate the interaction of flavonoids with the microbiota and hepatic alterations in obesity-induced rats/mice. Studies were searched in PubMed, ScienceDirect and LILACS databases. Experimental studies that evaluated the influence of flavonoids on the composition of the microbiota and on hepatic alterations were included. After applying all exclusion criteria, the review consists of 15 experimental studies. It was shown that obesity-induced and flavonoid-treated mice showed an increase in bacterial diversity, a reduction in the abundance of bacteria associated with the consumption of a high-fat diet, such as Firmicutes, Proteobacteria, and an increase in the abundance of bacteria such as Bacteroidetes, Verrucomibrobia, Akkermansia, and Bifidobacterium. associated with improved metabolic and pathological status. Furthermore, flavonoids are able to reduce oxidative stress and inflammation of liver tissue. Finally, an association was observed between the composition of the microbiota and hepatic cholesterol through the metabolism of bile salts. Therefore, positive effects are suggested through the administration of flavonoids. Manuscript 3: Serum AST and ALT markers, hepatic cytokine profile, intestinal microbiota composition and expression of p53, c-Myc, caspase-3 and PCNA genes were determined. There was no difference between the experimental groups for serum markers of ASL and ALT and hepatic cytokines. Supplementation with 5% and 10% DHSC altered the composition of the intestinal microbiota, increasing the abundance of the Lachnospiraceae, Ruminococcaceae and Clostridiaceae families and the Clostridum genus, important butyrate producers. Furthermore, supplementation with 5% and 10% DHSC increased caspase-3 and c-Myc expression, respectively. Therefore, phenolic compounds, anthocyanins and dietary fiber contributed to modulate the composition of the intestinal microbiota, in addition to influencing the expression of genes associated with cellular apoptosis. Keywords: Colorectal Cancer. Microbiota. Hibiscus. Flavonoids. Anthocyanins.