Natural inhibitors of digestive lipases offer promising alternatives to conventional obesity medications. This study screened nine medicinal plant extracts, identifying the ethanolic bark extract of Cinnamomum cassia as the most potent inhibitor for gastric and pancreatic lipases. Using an integrated approach combining bioactivity-guided fractionation and mass spectrometry, we isolated the highly active fraction, F3-1-1, which exhibited dose- and time-dependent inhibitory effects against human and porcine pancreatic lipases, as well as dog gastric lipase (DGL). Further mass spectrometry and peptide mass fingerprint analysis putatively annotated cinncassiol A-19 glucoside as a bioactive constituent. Notably, this compound was likely bound covalently to the catalytic peptide containing the Ser153 residue in DGL, characterized by a mass shift of +553.10 Da. Molecular docking simulations supported these suggestions, demonstrating stable interactions within the catalytic pocket of DGL through hydrogen and hydrophobic bond interactions. These findings highlight C. cassia as a promising source of natural anti-obesity agents.

Natural inhibitors of digestive lipases offer promising alternatives to conventional obesity medications. This study screened nine medicinal plant extracts identifying the ethanolic bark extract of Cinnamomum cassia as the most potent inhibitor for gastric and pancreatic lipases. Using an integrated approach combining bioactivity-guided fractionation and mass spectrometry, we isolated the highly active fraction, F3-1-1, which exhibited dose- and time-dependent inhibitory effects against human and porcine pancreatic lipases, as well as dog gastric lipase (DGL). Further mass spectrometry and peptide mass fingerprint analysis identified cinncassiol A-19 glucoside as the main bioactive constituent. Notably, this compound forms covalent complexes with the catalytic peptide containing the Ser153 residue in DGL, characterized by a mass shift of +553.10 Da. Molecular docking simulations supported these results, demonstrating stable interactions within the catalytic pocket of DGL through hydrogen and hydrophobic bond interactions. These findings highlight C. cassia as a promising source of natural anti-obesity agents.