Beta-Caryophyllene Attenuates the In Vitro Oxidation of LDL.

Background/Objectives: The oxidation of low-density lipoprotein (LDL) is a crucial step in atherogenesis. Beta-Caryophyllene (BCP) is a natural compound with established anti-oxidative and anti-inflammatory properties as shown in animal and cell culture studies. We examined whether BCP can impede LDL oxidation in an in vitro model. Methods: The anti-oxidative effect of BCP was evaluated in different concentrations (0, 25, 50, 100, and 150 µg/mL) with regard to scavenging reactive oxygen species (ROS) during LDL oxidation, which was initiated by the addition of copper chloride (CuCl2) in a concentration of 10 µmol/L. Lipid hydroperoxides (LPO), malondialdehyde (MDA), dienes, cell viability, and reactions of BCP with ROS according to Gibbs free energies were applied to determine the oxidation state of LDL. Results: Our findings indicated that BCP is highly efficient in inhibiting LDL oxidation in a dose-dependent manner in this in vitro model. The lipid hydroperoxide content in oxLDL was significantly lower in the presence of 100 µg/mL BCP compared to oxLDL without BCP (p < 0.0001). This corresponds to the MDA levels, which were significantly lower in the presence of 100 µg/mL BCP compared to oxLDL without BCP (p = 0.0393). Furthermore, a dose-dependent inhibition of diene formation in the LDL particle was observed in the presence of ascending BCP concentrations which corresponds to a decrease in the cytotoxicity of oxLDL in EA.hy926 cells in the presence of increasing concentrations of BCP. Moreover, BCP's anti-oxidant effectiveness exceeds that of the widely recognized anti-oxidant spermidine at equivalent concentrations. Our quantum chemical calculations showed that the reactions between BCP and hydroxyl radicals, hydroperoxyl radicals, or hydrogen peroxide are exergonic. We therefore conclude that BCP impedes the oxidation of LDL by its capability to scavenge (at least) these three reactive oxygen species. Conclusions: Our results indicate that BCP impedes the oxidation of LDL in vitro and therefore presumably has the potential to serve as an appropriate therapeutic agent to prevent atherogenesis and related (cardio)vascular diseases by balancing vascular oxidative stress. For this purpose, more prospective clinical studies in humans are required to assess the potential atheroprotective and health-promoting effects of BCP.