Protective effect of germacrane-type sesquiterpenoids from Chrysanthemum morifolium (Jinsi Huangju) against acetaminophen induced liver injury via inhibition of apoptosis.

Fifteen previously undescribed germacrane-type sesquiterpenoids (1-15) along with seven known analogues (16-22) were isolated from the flowers of Chrysanthemum morifolium Ramat. (Jinsi Huangju). Their structures were identified by analysis of the HRESIMS, NMR, ECD, IR spectra, and single-crystal X-ray diffraction. Among these, thirteen compounds (1, 3, 4, 6, and 13-21) exhibited protective effects against aminophenol (APAP)-induced toxicity in L-02 cells. The results were further validated by molecular docking studies and PI/Annexin V double staining assay. Mechanistic studies revealed that the hepatocyte apoptosis was suppressed through the inhibition of Bax and Caspase-3, and improved expression of Bcl-2 in APAP-exposed hepatic tissue and L-02 cells. This is the first ever report on the hepatoprotective activity of germacrane-type sesquiterpenoids of Jinsi Huangju flowers, supporting its nutraceutical value in liver disease management.