Protective effects of Butia capitata extract against colitis-driven colorectal tumorigenesis: Insights into its anti-inflammatory and antinociceptive activities

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BACKGROUND Colorectal cancer (CRC) remains among the most common causes of cancer-related deaths worldwide. Ulcerative colitis and Crohn’s disease are inflammatory bowel diseases characterized by recurrent episodes of inflammation in the gastrointestinal tract, which increase the risk of developing CRC. One of the main pathways activated during the inflammatory process is sphingosine-1-phosphate (S1P). S1P activates the signal transducer and activator of transcription 3 (STAT3). Phosphorylated STAT3 inhibits apoptotic pathways, promoting tumorigenesis and, consequently, the development of CRC. Compounds with antioxidant potential, such as the hydroalcoholic extract of Butia capitata fruit pulp (HAEBC), may act to reduce oxidative stress, thereby decreasing inflammatory events. AIM To evaluate the anti-inflammatory and antinociceptive effects of HAEBC in an experimental colitis model and to investigate, in silico , the interaction of its phenolic compounds with molecular targets. METHODS HAEBC was prepared using a modified protocol and administered in 10% dimethyl sulfoxide in saline. Male and female Swiss mice were used for pain tests induced by acetic acid, formalin, and carrageenan. Acute colitis was induced by intracolonic administration of acetic acid after pretreatment with HAEBC, mesalazine, or saline. Macroscopic lesions, histological changes, and visceral hyperalgesia (von Frey test) were evaluated. Statistical analysis was performed using one-way analysis of variance followed by Tukey’s test. In silico analyses explored potential anti-inflammatory targets of HAEBC compounds, including sphingosine kinase 1 (SPHK1), indoleamine 2,3-dioxygenase 1 (IDO1), and cyclooxygenase-2 (COX-2). RESULTS Pre-treatment with HAEBC at doses of 30 and 100 mg/kg significantly reduced contortions in mice (58% and 49%, respectively), with time-dependent effects. The extract inhibited both the neurogenic and inflammatory phases of the formalin test, decreasing paw flinching and licking time, indicating action on nociceptors and inflammatory mediators such as prostaglandins and cytokines. HAEBC at 100 mg/kg also reduced carrageenan-induced paw edema by 63%. In acute colitis, treated mice showed more than 75% inhibition of macroscopic lesions and preserved colon architecture, unlike mesalazine-treated animals. In the von Frey test, HAEBC at 300 mg/kg outperformed both the 10 mg/kg dose and mesalazine. Docking analyses indicated that gallic acid, p-hydroxybenzoic acid, and chlorogenic acid interact with SPHK1, IDO1, COX-2, and sphingosine 1-phosphate receptor 1, with chlorogenic acid forming the most stable complexes. CONCLUSION HAEBC exhibited anti-inflammatory and antinociceptive effects, preserving tissue integrity and reducing hyperalgesia. The proposed molecular interactions remain hypothetical. Implications for tumorigenesis are indirect and require validation using chronic models and molecular analyses.

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