Identification of bioactive compounds of Phyllanthus emblica L. and its role in alleviating endothelial inflammation and lipid deposition via YAP protein phosphorylation and cytoplasmic sequestration.
BACKGROUND Phyllanthus emblica L. (PE) is a traditional medicinal and edible plant with cardiovascular protective potential, but its bioactive compounds and molecular targets are unclear. This study aimed to identify the core in vivo bioactive compounds and elucidate their mechanisms in attenuating lipid deposition and endothelial inflammation via the Hippo-YAP signal pathway. METHODS UPLC-Q-Exactive-MS was utilized to profile constituents in PE extract, medicated rat serum, and zebrafish tissues. An in vitro ox-LDL-induced HUVEC model and an in vivo high-cholesterol diet induced zebrafish model were established to analyze the efficacy and mechanism of the drug and its bioactive compounds. Molecular docking, Drug Affinity Responsive Target Stability (DARTS), Cellular Thermal Shift Assay (CETSA), and Surface Plasmon Resonance (SPR) were employed to verify direct drug-target interactions. RESULTS 128 compounds were identified in extract, and 14 and 8 absorbed constituents in serum and tissues, respectively. Intersection analysis and functional screening pinpointed corilagin and ethyl gallate as primary bioactives. They directly bound YAP with high affinity, enhancing its thermal and proteolytic stability, facilitating phosphorylation and cytoplasmic sequestration, and preventing nuclear translocation and pro-inflammatory gene transcription. In vivo, PE extract and compounds significantly reduced vascular lipid plaques, TC/TG/LDL-C, and inflammatory markers CONCLUSIONS: PE protects against endothelial injury and lipid deposition through corilagin and ethyl gallate, which directly bind YAP, enforcing cytoplasmic retention and shutting down inflammation, offering a natural YAP-targeted strategy for cardiovascular protection.