Rosa Iris Godínez-Santillán

Bioactive compounds in food contribute to reducing the risk of developing colon cancer by modulating the gut microbiota. We have recently demonstrated that garambullo (Myrtillocactus geometrizans), an endemic fruit of Mexico rich in bioactive compounds, attenuates aberrant crypt foci in an animal model. However, its potential to modulate the gut microbiota is unknown. The main objective of this study was to evaluate whether its consumption modulates colon carcinogenesis by altering the microbiota in an in vivo model induced by azoxymethane and dextran sulfate sodium (AOM/DSS). Fecal samples were collected from twelve male Sprague-Dawley rats and analyzed for microbiota composition after 0, 8, and 16 weeks of treatment with saline (control), AOM/DSS, garambullo (G), or residue of garambullo (RG) with AOM/DSS (G+AOM/DSS and RG+AOM/DSS, respectively). Characterization of the microbiome was based on the conserved region of the 16S rRNA V3-V4 gene, and analyzed by the ZymoBIOMICS’ Targeted Metagenomics Sequencing (Zymo Research) service. In an animal model induced with AOM/DSS for 8 weeks, consumption of G and its residue increased the bacterial genera Shuttleworthiia, Subdoligranulum, Lactobacillus, Faecalibacterium, and Alloprevotella (p < 0.05). Consumption of G and its residue allowed the proliferation of bacteria that produce short-chain fatty acids and are associated with protective mechanisms of the colon.

This research identified the bioactive compounds and antioxidant capacity of the extractable (EP) and non-extractable (NEP) polyphenol fractions of berrycactus (BC). Additionally, the effects of BC and its residue (BCR) on preventing AOM/DSS-induced early colon carcinogenesis were evaluated in vivo. Male Sprague Dawley rats were randomly assigned to six groups (n = 12/group): healthy control (C), AOM/DSS, BC, BCR, BC+AOM/DSS, and BCR+AOM/DSS. NEP was obtained through acid hydrolysis using H₂SO₄ and HCl (1 M or 4 M). The HCl-NEP fraction exhibited the highest total phenolic and flavonoid content, while condensed tannins were more abundant in the H₂SO₄-NEP fraction. A total of 33 polyphenols were identified by UPLC-QTOF-MSE in both EP and NEP, some of which were novel to BC. Both NEP hydrolysates demonstrated significant total antioxidant capacity (TEAC), with HCl-NEP exhibiting the highest ORAC values. The BC+AOM/DSS and BCR+AOM/DSS groups exhibited fewer aberrant crypt foci (p < 0.05), reduced colonic epithelial injury, and presented lower fecal β-glucuronidase activity, when compared to AOM/DSS group. No differences in butyric acid concentrations were observed between groups. This study presents novel bioactive compounds in EP and NEP from BC that contribute to chemopreventive effects in early colon carcinogenesis, while reducing fecal β-glucuronidase activity and preserving colonic mucosal integrity.

Aberrant crypt foci (ACF) is the precursor lesion of colorectal carcinogenesis (CRC), one of the most common malignancies in the world. Many studies have reported that people with higher phytochemical intake are at a reduced risk of developing ACF. One example of the botanical potential of preventive plant products is Cnidoscolus aconitifolius (CA), commonly known as Chaya. This study evaluated the phenolic profile of CA and the effects of the daily consumption of CA leaf infusion on the formation of ACF, histopathological lesions, and molecular biomarkers after azoxymethane (AOM) and dextran sulfate sodium (DSS) induced premalignant colon lesions in rats treated with for 16 and 32 weeks. The phenolic composition of the CA infusion was identified by reversed phase-high performance liquid chromatography-diode array detection (RP-HPCC-DAD). After sacrifice, a 4 cm segment was collected from the distal part of the colon and stained with methylene blue to look for ACF. Furthermore, 4 μm of colon, liver, and kidney was collected and stained with hematoxylin and eosin for histopathological analysis, along with 7 μm of colon for immunohistochemistry analysis. Eleven phenolic compounds were identified in the infusions, and ACF formation was reduced by 29.5% at the subchronic and by 64.6% at chronic stages. Lesions on kidney, liver, and colon tissue were also reduced. Our data suggest that CA treatment has preventive effects against AOM-/DSS-induced premalignant colon lesions in colon rats at the promotion level, inhibiting the cell proliferation of early neoplastic lesions and colonic inflammation through the decrease of β-catenin by 41.8% at the subchronic stage and 29% at the chronic stage, along with a 46.2% reduction of cyclooxygenase 2 (COX-2) at long term, despite a high expression of NF-κB (30.3% at the subchronic stage and 22.8% at the chronic stage).

Antecedentes y Objetivos: Cnidoscolus aconitifolius es una especie arbustiva que se utiliza como planta ornamental, medicinal y alimentaria en varias partes del mundo, conocida en México como chaya. Existe poca investigación científica publicada sobre su composición fenólica y su capacidad antioxidante. El objetivo de este estudio es determinar la caracterización fenólica y la capacidad antioxidante de extractos hidroalcohólicos (metanol-agua y etanol-agua) en diferentes proporciones de hojas de C. aconitifolius crudas y hervidas.Métodos: Se realizó un cultivo de C. aconitifolius en el campus de la Universidad de Querétaro (México; 2014) utilizando estacas leñosas. Durante el verano de 2016 se realizaron muestreos de hojas de todas las plantas cultivadas. El contenido de compuestos fenólicos totales (CFT), el contenido total de flavonoides (CTF) y la capacidad antioxidante se determinaron en extractos de metanol-agua (50:50 y 80:20) y de etanol-agua (50:50 y 80:20) provenientes de hojas crudas y hervidas. Además, se identificaron y cuantificaron compuestos fenólicos de cada uno de los extractos mediante el método RP-HPLC-DAD.Resultados clave: Se identificaron y cuantificaron 11 compuestos fenólicos en la especie C. aconitifolius: ácido gálico, ácido vanílico, vainillina, ácido clorogénico, ácido cafeico, ácido ferúlico, ácido rosmarínico, ácido p-cumárico, resveratrol, luteolina y apigenina. En general, las hojas hervidas mostraron una mayor capacidad antioxidante que las hojas crudas. Se observaron diferencias en el contenido de compuestos fenólicos debido al tipo de solvente y mezcla utilizada, siendo el extracto etanólico 80:20 proveniente de las hojas hervidas de chaya el que mostró mayor contenido de polifenoles.Conclusiones: Hervir las hojas incrementó el contenido de compuestos fenólicos en los extractos analizados. Los resultados de este estudio indican que las hojas de chaya son una fuente rica de antioxidantes naturales.