Inhaled volatile β-caryophyllene is incorporated into the aortic wall and attenuates nicotine-induced aorta degeneration via a CB2 receptor-dependent pathway

β-caryophyllene (BCP) is a volatile bicyclic sesquiterpenoid found in essential oils obtained from several spices such as black pepper, oregano, basil, rosemary, cinnamon, and clove. BCP is a selective agonist of cannabinoid receptor 2 (CB2 receptor), and orally administered BCP exhibits various biological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. However, it is still unclear how volatile BCP affects living organisms. We previously reported that inhaled BCP is transferred to sera and organs in mice; additionally, metabolomic analysis revealed inhaled BCP affect the dynamics of metabolites in the livers of mice. These data suggest that inhaled BCP may affect several biological activities by stimulating biological systems. In this study, we evaluated the effects of BCP inhalation on nicotine-induced degeneration of the aortic wall. In the group of mice which inhaled volatile BCP, nicotine-induced increases in elastic fiber degradation and matrix metalloproteinase-2 (MMP-2)-positive areas were attenuated. In addition, BCP improved the nicotine-induced stiffness of aortae and vulnerability to aortic rupture. In cultured aortae, the suppressive effects of BCP were inhibited by the CB2 receptor inhibitor AM630. These results suggest that inhaled BCP is incorporated into the aortic wall and prevents nicotine-induced degeneration of the aorta via a CB2 receptor-dependent pathway.