Lu, X., et al. Natural products targeting tumour angiogenesis.

Lu, X., et al. Natural products targeting tumour angiogenesis.

Br J Pharmacol, 2025 May, 182(10):2094-2136. PMID: 37680009

• This comprehensive review highlights the potential of natural products derived from plants, animals, and microorganisms to target tumor angiogenesis, a critical process for tumor growth and metastasis. It discusses the mechanisms by which pro- and anti-angiogenic factors regulate blood vessel formation in tumors and reviews existing anti-angiogenic therapies, including monoclonal antibodies, VEGFR inhibitors, and fusion proteins. The review emphasizes various natural agents, such as polyphenols, alkaloids, terpenoids, saponins, and polysaccharides, detailing their mechanisms of action, primarily through modulating VEGF pathways and other angiogenic signals. It also addresses the challenges of bioavailability, dosage, side effects, and resistance, proposing future strategies for clinical translation, such as combination therapies and discovery of novel natural compounds, to enhance their efficacy in cancer treatment.
• The review indicates that natural products containing a combination of saponins, polyphenols, and polysaccharides may have synergistic or complementary anti-angiogenic effects. For instance, saponins can exhibit anti-angiogenic activity by modulating key signaling pathways such as VEGFR, PI3K/AKT/mTOR, and JAK2-STAT3, while polyphenols can inhibit MMP activity and VEGF production, and polysaccharides can suppress angiogenesis through modulation of HIF-1α and VEGFR expression. Combining these bioactive components could potentially enhance the overall anti-angiogenic efficacy by targeting multiple pathways involved in tumor vascularization. However, the review also emphasizes that the mechanisms underlying such combined effects require further investigation, and the formulation challenges must be considered. Therefore, such multi-component natural products hold promising therapeutic potential, but thorough in vivo and clinical studies are necessary to evaluate their safety, efficacy, and optimal dosing strategies.
• Comments from DK: In crude saponin extracts of Quillaja saponaria (such as aqueous or partially purified bark extracts), the following classes of molecules are typically present: saponins, polyphenols (flavonoids, tannins), polysaccharides (pectins, arabinogalactans, hemicelluloses), and terpenoids.

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