Bioassay-guided and DeepSAT + SMART-driven identification of hepatoprotective phenolics from the fruits of Phyllanthus emblica.

To explore potential protective effects of natural products against alcohol-induced liver disease, a bioactivity-driven approach and HSQC-based DeepSAT and SMART were employed. Twelve phenolics, including four previously uncharacterized compounds (1-4), were identified from the fruits of Phyllanthus emblica. Their structures were elucidated as gallic acid analogs through comprehensive spectroscopic analysis, including HRESIMS and NMR methods. Network pharmacology predicted that compounds 1-12 may target on AKT1, TNF, and NFKB1, with potential to improve alcohol-induced liver injury, as suggested by Swiss Target Prediction. Compounds 1-4, 6, 8, and 9 exhibited significant protective effects against alcohol-induced liver damage in NCTC-1469 cells at a concentration of 20 μg/mL. Notably, compound 4 was found to exert its anti-alcoholic liver injury effect via the TLR4/NF-κB signaling pathway.