Pulsatilla chinensis Saponins as Multitargeted Anticancer Agents: A Mini-Review of Molecular Mechanisms and Therapeutic Potential
Jizhuo Sun, Fangfang Nie, Xue Sun, Yuanhe WangIntroduction:
This review comprehensively summarizes the multi-target antitumor molecular mechanisms and therapeutic potential of key triterpenoid saponins Anemoside B4 (AB4), Pulsatilla Saponin D (PSD), Pulsatilla Saponin A (PSA), PC saponin (PC), and Anemoside A3 (AA3) derived from Pulsatilla chinensis.
Methods:
Relevant literature across major databases up to early 2025 was systematically reviewed, categorizing findings by saponin type to analyze structure-activity relationships. Additionally, a Pan-Assay Interference Compounds (PAINS) analysis was conducted using the SwissADME platform to verify the target specificity of their core structures.
Results:
These saponins exhibit highly structure-dependent, specific anticancer mechanisms. Specifically, AB4 induces apoptosis and autophagy; PSD inhibits angiogenesis and blocks autophagic flux; PSA triggers DNA damage responses and cell cycle arrest; PC saponins disrupt tumor glycolytic energy metabolism; AA3 remodels the tumor immune microenvironment by promoting anti-tumor M1 macrophage polarization. The PAINS analysis confirmed that these effects originate from specific target modulation rather than non-specific membrane disruption.
Discussion:
The precise mechanisms observed demonstrate that subtle structural variations in the saponin backbone dictate specific signaling outcomes. Crucially, the exclusion of pan assay interference compounds (PAINS) confirms that these biological effects stem from specific target modulation rather than non-specific membrane disruption. These findings highlight the pleiotropic advantage of Pulsatilla saponins, allowing them to simultaneously intervene in multiple oncogenic signaling pathways and overcome potential drug resistance.
Conclusion:
Pulsatilla saponins represent promising multi-target anticancer candidates. Future studies should focus on improving their pharmacokinetic properties and delivery systems to facilitate clinical translation.