An SPR-based active ingredient recognition strategy for identifying PLK1-targeting withanolides as natural...

The research on bioactive components of natural products (NPs) is confronted with cumbersome separation processes and poor targeting specificity. How to efficiently and precisely identify active components remains a critical challenge in NPs research. Our previous research has confirmed that Tubocapsenolide A (TA), a major withanolide isolated from Tubocapsicum anomalum, induces ferroptosis in colorectal cancer (CRC) by targeting PLK1. In order to efficiently and accurately identify PLK1-targeting constituents from Solanaceae plants, we developed a surface plasmon resonance biosensor-based active ingredient recognition system targeting PLK1 (PLK1-SPR-AIRS). Through systematic application of PLK1-SPR-AIRS, we identified multiple withanolides targeting PLK1 from extracts of different Solanaceae plants. Notably, these withanolides also demonstrate potent ferroptotic induction in CRC cells, where their efficacy correlates directly with PLK1-binding affinity. Our findings demonstrate that withanolides represent a novel class of natural PLK1-targeting ferroptosis inducers. Collectively, we successfully established the PLK1-SPR-AIRS for the efficient and precise identification of target-specific bioactive components from Solanaceae medicinal plants. This study not only accelerates the exploitation of Solanaceae medicinal resources, but also establishes a strategic framework for precise and efficient identification of bioactive natural product constituents, while providing promising candidate compounds for treatment of CRC.