Conclusions
The provided scientific evidence to support that SGI combination from SND could be used as a prebiotic agent for DCM. Importantly, the proposed two-dimensional CMMC-TOFMS analytical system provides a high-throughput screening strategy for mitochondria-targeted compounds from natural products, which could be applied to other subcellular organelle models for drug discovery.
Methods
The AIC were screened by a novel comprehensive two-dimensional cardiac mitochondrial membrane chromatography (CMMC)-TOFMS analysis system and further validated by cell viability, reactive oxygen species (ROS) generation, ATP level, and mitochondrial membrane potential in DOX-induced H9c2 cell injury model. Then, an integrated model of cardiac mitochondrial metabolomics and proteomics were applied to clarify the underlying mechanism in vitro.
Results
The CMMC column lifespan was significantly improved to more than 10 days. Songorine (S), neoline, talatizamine, 8-gingerol (G) and isoliquiritigenin (I), exhibiting stronger retention on the first-dimension CMMC column, were screened to have protective effects against DOX cardiotoxicity in the H9c2 cell model. S, G and I were selected as an AIC from SND according to the bioactivity evaluation and the compatibility theory of SND. The combined in vitro use of S, G and I produced more profound therapeutic effects than any component used individually on increasing ATP levels and mitochondrial membrane potential and suppressing intracellular ROS production. Moreover, SGI attenuated DCM might via regulating mitochondrial energy metabolism and mitochondrial dysfunction. Conclusions: The provided scientific evidence to support that SGI combination from SND could be used as a prebiotic agent for DCM. Importantly, the proposed two-dimensional CMMC-TOFMS analytical system provides a high-throughput screening strategy for mitochondria-targeted compounds from natural products, which could be applied to other subcellular organelle models for drug discovery.