Eduardo E. Valdez-Morales

Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide and a leading cause of cancer-related mortality. Despite advances in surgery, chemotherapy, and targeted therapies, many CRC patients experience limited efficacy, toxicity, or drug resistance. Thus, complementary therapeutic strategies with an improved safety profile are needed. Plant-derived polyphenols emerge as promising candidates for CRC treatment. Methods: This review compiles in vitro, in vivo, and clinical evidence on the anticancer activity of polyphenols in CRC. Polyphenols, such as curcumin, resveratrol, quercetin, and flavonoids, are analyzed, with emphasis on molecular mechanisms and chemopreventive potential. Results: In vitro studies consistently demonstrate that these compounds exert anticancer effects by modulating multiple pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, STAT3, and MAPK/ERK, promoting apoptosis and regulating oxidative stress and inflammation. In vivo studies indicate that curcumin, resveratrol, quercetin, epigallocatechin gallate (EGCG), genistein, luteolin, and fisetin significantly reduce tumor volume, polyp formation, and aberrant crypt foci (ACF). Curcumin has been extensively evaluated in trials, with some studies demonstrating reductions in ACF and improvements in inflammatory markers and quality of life, while others have demonstrated no significant clinical benefit. Discussion: Preclinical evidence supports the chemopreventive role of polyphenols. Preliminary clinical trials also suggest therapeutic potential for CRC prevention and treatment; however, large-scale, well-controlled clinical trials are required to confirm their safety and efficacy. Conclusion: Plant-derived polyphenols represent promising complementary strategies for CRC prevention and therapy. Future research should prioritize compounds with strong preclinical evidence, standardized formulations, optimized delivery strategies, and rigorously designed randomized trials to facilitate integration into clinical oncology practice.

Background: Diabetic gastrointestinal dysfunction is a common complication of long‐standing diabetes and poorly controlled hyperglycemia, often associated with considerable morbidity. However, the cellular mechanisms that underlie the diabetic impairment of the intestine remain poorly understood. In the present study, we examined whether alterations in myenteric neuron excitability contribute to diabetic intestinal dysfunction. Methods: Type 2 diabetic mice were generated by administering a cafeteria diet for 21 weeks and an intraperitoneal injection of streptozotocin. Fasting blood glucose assessment and glucose and insulin tolerance tests confirmed the development of diabetes. The effect of diabetes on gut contractility was tested in an isolated organ bath, and patch‐clamp recordings were conducted to measure neuronal biophysical properties. Key Results: Type 2 diabetic mouse colons had a decreased twitch force amplitude and a decrease in the frequency of rhythmic spontaneous contractions. Moreover, S‐myenteric neurons of type 2 diabetic mice exhibited reduced excitability with a significant increase of 41% in rheobase. Incubation of naïve myenteric neurons with colonic supernatants from type 2 diabetic mice recapitulated the effects on rheobase. Finally, the total voltage‐gated sodium currents were significantly decreased in myenteric neurons incubated with diabetic colonic supernatants. Conclusion and Inferences: The decreased excitability and downregulation of total voltage‐gated sodium currents in the myenteric neurons of type 2 diabetic mice could partially explain the cellular mechanisms underlying the colonic dysmotility observed in patients with diabetes. Targeting voltage‐gated sodium channels may represent a novel therapeutic approach for modulating diabetic intestinal dysfunction.

The role of P2X ionotropic receptors in the behavior of purinergic signaling on pathophysiological processes has been widely studied. In recent years, the important participation of P2X receptors in physiological and pathological processes, such as energy metabolism, characteristic inflammatory responses of the immune system, and nociceptive activity in response to pain stimuli, has been noted. Here, we explore the molecular characteristics of the P2X receptors and the use of the different agonist and antagonist agents recently described, focusing on their potential as new therapeutic targets in the treatment of diseases with emphasis on obesity, diabetes, and some of the complications derived from these pathologies.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Its treatment options have had a limited impact on cancer remission prognosis. Therefore, there is an ongoing need to discover novel anti-cancer agents. Medicinal plants have gained recognition as a source of anti-cancer bioactive compounds. Recently, ethanolic extract of L. virginicum stems ameliorated dinitrobenzene sulfonic acid (DNBS)-induced colitis by modulating the intestinal immune response. However, no scientific study has demonstrated this potential cytotoxic impact on colon cancer cells. The objective of this study was to evaluate the cytotoxic effect of the methanolic extract of L. virginicum (ELv) on a human colorectal adenocarcinoma cell line (Caco-2) and to identify and quantify the phenolic compounds present in ELv extracts by liquid chromatography-mass spectrometry analysis. The cytotoxic activity was assessed using cell viability assays by reduction in the compound 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH). MTT and LDH assays revealed that the ELv decreases cell viability in the Caco-2 cell line in a concentration-dependent manner. Cell death was a result of DNA fragmentation and p53-mediated apoptosis. Eight phenolic acids and five flavonoids were identified and quantified in the stems. In conclusion, our findings demonstrate that the extract of L. virginicum possesses cytotoxic properties on Caco-2 cell line, suggesting that it could be a potential source of new drugs against CRC.