Antioxidant, Antimicrobial, and Membrane‐Modulating Effects of Inula helenium L. Root Extract: Protection Against Doxorubicin‐Induced Hepatic Oxidative Stress

ABSTRACT Inula helenium L. root extract has been investigated for antioxidant and antimicrobial activity; however, its phytochemical profile, antimicrobial effects, membrane interactions, and in vivo protection against oxidative injury have not previously been evaluated within a single framework. This study investigated the phytochemical composition, antioxidant and antimicrobial activities, membrane interactions, and protective effect of ethanolic I. helenium L. root extract against doxorubicin (DOX)‐induced hepatic oxidative stress. Tannins were the predominant phytochemical class (247.72 ± 10.00 µg/g DW), followed by phenolic acids (7.99 ± 0.06 µg/g DW) and sesquiterpene lactones (0.711 ± 0.05 µg/g DW). LC‐MS tentatively identified alantolactone/isoalantolactone (C 15 H 20 O 2 ). The extract showed moderate antioxidant activity and selective antimicrobial effects, with the strongest activity against Candida krusei and Yersinia enterocolitica . Differential scanning calorimetry demonstrated concentration‐dependent fluidization of DPPC lipid bilayers, indicating direct membrane interaction. In vivo, extract administration (200 and 400 mg/kg, p.o.) significantly reduced DOX‐induced hepatic malondialdehyde levels, restoring them to intact‐control values ( p < 0.001), despite moderate in vitro radical‐scavenging activity. Acute toxicity testing showed no mortality at 5000 mg/kg. Overall, I. helenium L. root extract protects against DOX‐induced hepatic oxidative stress through complementary biochemical and membrane‐level mechanisms, supporting its potential for nutraceutical and pharmaceutical applications.