Liu, Y.F., et al. Anti-Colorectal Cancer Mechanisms of Natural Saponins: Advances and Therapeutic Implications. Chin J Integr Med, 2025 Oct 15.

Liu, Y.F., et al. Anti-Colorectal Cancer Mechanisms of Natural Saponins: Advances and Therapeutic Implications. Chin J Integr Med, 2025 Oct 15. PMID: 41091371

• This paper aims to systematically review the anti-colorectal cancer (CRC) effects of natural saponins, plant-derived compounds known for their low toxicity and multifaceted biological activities. Given the rising incidence and mortality of CRC and the limitations of current treatments, such as high side effects, resistance, and metastasis, the study explores the potential of saponins as novel therapeutic agents. It highlights their ability to inhibit tumor proliferation, induce apoptosis, regulate autophagy, modulate energy metabolism, and reshape the tumor microenvironment, including the gut microbiota, offering a promising, multi-target strategy for CRC prevention and treatment.
• The paper reveals that natural saponins exert potent anti-CRC effects through various mechanisms, including inhibiting tumor cell proliferation by targeting pathways like Wnt/β-catenin, STAT3/MMP, and PI3K/Akt, and inducing apoptosis via modulation of Bcl-2, caspases, and related signaling pathways. They also suppress epithelial-mesenchymal transition (EMT), regulate autophagy, and reprogram energy metabolism by disrupting lipid, glucose, and amino acid pathways, often through oxidative and ER stress responses. Additionally, saponins modulate the tumor microenvironment by enhancing immune responses, polarizing macrophages from M2 to M1, and remodeling gut microbiota to suppress inflammation. 
• Despite these promising preclinical findings, there remains a significant gap in clinical validation, safety evaluation, and understanding of bioavailability and mechanistic interactions among these pathways. Additionally, the multifaceted mechanisms of saponins underscore the complexity of fully understanding and harnessing their therapeutic potential. The discussion emphasizes the promising anti-CRC effects of natural saponins but also notes the necessity for further research, especially large-scale clinical trials, to validate efficacy and safety in humans. 

Click here to access the full scientific paper.