Interaction of β-Caryophyllene with a Simplified Membrane Model and Its Growth-Inhibitory Effect Against Escherichia coli ATCC 25922

The increasing prevalence of antimicrobial resistance in bacteria highlights the need for alternative membrane-active compounds with favorable safety profiles. β-Caryophyllene (BCP), a bicyclic sesquiterpene, has demonstrated antimicrobial effects; however, its biological responses in Gram-negative bacteria and associated membrane interactions remain insufficiently characterized. In this study, the growth inhibitory effect of BCP against E. coli ATCC 25922 was evaluated through OD595 growth kinetics, while hemocompatibility was assessed using sheep erythrocytes, and cannabidiol (CBD) was included as a comparative control. To investigate membrane-associated effects, differential scanning calorimetry (DSC) was performed using DPPE/DPPG (8:2) bilayers as a simplified phospholipid membrane model. BCP inhibited bacterial growth with an IC50 of 0.83 mg/mL and exhibited low hemolytic activity (2.92% at 1 mg/mL). DSC analyses revealed concentration-dependent shifts in phase transition temperature and reductions in transition enthalpy (ΔH kJ/mol) 36% and 82% for BCP-5 and CBD-10 according to the control, indicating alterations in lipid organization and membrane thermotropic behavior. In contrast, CBD showed greater growth inhibitory potency (IC50 of 0.042 mg/mL) but more pronounced disruption of membrane organization. Overall, these findings suggest that BCP exhibits moderate growth inhibition associated with membrane related effects and low hemolytic activity, providing insights into the relationship between physicochemical properties, membrane interactions, and biological responses.