Mechanisms of Traditional Chinese Medicine-Derived Alkaloids in Colorectal Cancer Therapy: Molecular Targets, Preclinical Evidence, and Translational Prospects.

Alkaloids are nitrogen-containing basic compounds derived from plants, characterized by complex cyclic structures. They serve as key active components in most traditional Chinese medicines (TCM) and demonstrate significant clinical value in colorectal cancer therapy. In recent years, TCM-derived alkaloids represented by berberine, matrine, and camptothecin have attracted widespread attention due to their remarkable anti-tumor activity. Research indicates that these compounds exert synergistic effects across multiple pathways and targets by modulating key signaling pathways, including Wnt/β-catenin, PI3K/Akt, etc. They play important roles in regulating tumor cell proliferation, apoptosis, invasion, and reversal of drug resistance. However, despite the significant multi-pathway and multi-target effects demonstrated by alkaloid compounds, current research has yet to provide a comprehensive and systematic review of their intervention effects on colorectal cancer. To address this gap, this review systematically examines the mechanisms of action of TCM-derived alkaloids and their nano-formulations in colorectal cancer treatment. It summarizes the molecular pathway networks regulated by these representative alkaloids and discusses their potential clinical benefits and current limitations.Building on this foundation, this paper further outlines future research directions, including structure optimization based on molecular structure considerations, targeted drug design strategies, and the prospects of alkaloid nanodelivery systems in clinical translation. The aim is to establish a systematic research framework for alkaloid-based colorectal cancer therapy and provide a theoretical basis for developing novel high-efficiency, low-toxicity treatment strategies.