AVALIAÇÃO DA TOXICIDADE E DA ATIVIDADE BIOLÓGICA IN VITRO E IN VIVO DO CLADÓDIO DE Cereus jamacaru DC. (MANDACARU) EM MODELOS DE INFLAMAÇÃO INTESTINAL E CÂNCER COLORRETAL
Colorectal cancer associated with colitis; Cereus; Colitis; Flavonoids; Immunomodulation;
Cereus jamacaru DC. (mandacaru) is a cactus species native to the Brazilian Caatinga
biome, traditionally used to treat inflammatory and gastrointestinal disorders, and whose
biological potential has increasingly attracted scientific interest. This study aimed to
evaluate the toxicity and biological activity, both in vitro and in vivo, of the C. jamacaru
extract in experimental models of intestinal inflammation and colitis-associated
colorectal cancer (CAC). Chemical characterization by LC-MSⁿ identified 17 flavonoids
in the extract, predominantly glycosylated derivatives of quercetin and kaempferol.
Toxicological assays demonstrated an adequate safety profile, with no relevant
behavioral, biochemical, or histopathological alterations. In dextran sulfate sodium
(DSS)-induced acute colitis and DNBS-induced relapsing chronic colitis models,
treatment with C. jamacaru exerted anti-inflammatory and antioxidant effects, as
evidenced by reduced myeloperoxidase activity and malondialdehyde levels, along with
increased reduced glutathione. In DSS-induced acute colitis, flow cytometry analyses
revealed modulation of inflammatory cell populations, with reductions in proinflammatory lymphocytes and circulating monocytes, accompanied by decreased
expression of inflammatory cytokines and restoration of genes associated with epithelial
barrier integrity, resulting in improved colonic histology. In the CAC model, the extract
reduced tumor number and volume, decreased cellular proliferation, and preserved tissue
architecture, effects associated with modulation of the Wnt/β-catenin, NF-κB, and COX-
2 signaling pathways. Collectively, these findings indicate that C. jamacaru exhibits a
favorable safety profile and attenuates chronic intestinal inflammation while modulating
key molecular mechanisms involved in carcinogenesis, supporting its potential as a
promising therapeutic candidate for chronic intestinal diseases.