Decoding the anti-glioma potential of saponins: structure-activity relationships, mechanism and development strategy

Glioma remains a critical challenge in neuro-oncology due to highly invasive behavior and limited treatment options. Saponins, a structurally diverse class of natural glycosides, have shown great potential as anti-glioma agents owing to their significant bioactivity and multi-target pharmacological properties. This review systematically summarizes the cytotoxicity of saponin compounds with anti-glioma activity, focuses on the analysis of their structure-activity relationships (SARs), elaborates in detail on the anti-glioma mechanisms of action exerted by different saponins, and corresponding solutions faced by saponins in clinical application. Saponins with anti-glioma activity are categorized into steroidal and triterpenoid types, and the key structural features and functional groups responsible for their efficacy are elucidated. Furthermore, we comprehensively summarize the core mechanisms by which saponins exert anti-glioma effects, including cell cycle arrest, apoptosis induction, suppression of invasion and migration, anti-angiogenesis, autophagy regulation, and reversal of drug resistance. Combined with the structural characteristics of saponins, we further discussed the bottleneck problems faced by this class of compounds in the process of drug development, as well as the targeted coping strategies. This study not only strengthens the theoretical foundation of saponins as anti-glioma lead compounds but also establishes a rational framework for their structural optimization and development into novel therapeutics.