Natural products targeting the Nrf2 signaling pathway: potential targets and intervention strategies for the prevention and treatment of colorectal cancer

Colorectal cancer (CRC) is a highly prevalent gastrointestinal malignancy worldwide, characterised by insidious onset, rapid progression, high tendency for recurrence and metastasis, and resistance to chemotherapy. It poses significant challenges for clinical management and has become a major public health issue threatening human health. Current clinical treatments for CRC remain significantly limited. Traditional chemotherapeutic agents exhibit poor selectivity and pronounced toxic side effects, and long-term use readily induces tumour resistance, resulting in suboptimal therapeutic outcomes. Consequently, the identification of highly effective and safe core therapeutic targets and novel intervention strategies holds significant clinical value. The Nrf2 signalling axis is a core pathway regulating the body's redox homeostasis, inflammatory responses, and the biological behaviour of tumour cells. Abnormal activation of this pathway can drive the proliferation, invasion, and metastasis of CRC cells, inhibit tumour cell apoptosis, and simultaneously mediate the development of chemotherapy resistance, making it a key molecular target involved in the onset and progression of CRC. Due to their widespread sources, structural diversity, low toxicity, and unique ability to exert synergistic regulation across multiple targets and pathways, natural products represent a vital resource for the development of novel anticancer drugs. A substantial body of research has demonstrated that various bioactive natural products can modulate the mode of cell death in CRC cells, inhibit malignant progression, reverse drug-resistant phenotypes, and improve the tumour immune microenvironment by specifically regulating Nrf2 and the expression of its downstream target genes. This article elucidates the core regulatory mechanisms of the Nrf2 signalling axis in the progression of CRC and summarises the anti-CRC effects and molecular mechanisms of various natural products that target this pathway. It analyses the application advantages and translational bottlenecks of natural products, providing a theoretical basis and new research insights for the development of novel natural anti-CRC drugs and the optimisation of clinical combination therapy regimens.