β-Caryophyllene as a Novel Modulator of the Renin-Angiotensin System: A Path to Reduce Inflammation and Restore Taste Function.

Background/Objectives: Dysgeusia is a taste disorder commonly associated with chronic inflammation, reducing the quality of life, particularly in ageing populations or individuals with non-communicable chronic diseases. This study aimed to evaluate the effect of β-Caryophyllene, a natural sesquiterpene and agonist of the cannabinoid receptor 2 (CB2), on dysgeusia through an analysis of inflammation, Renin-Angiotensin System (RAS) and taste perception. Methods: Male BALB/c mice were subjected to a dysgeusia model induced by molecular mimicry with lipopolysaccharide. Animals received intraperitoneal injections of lipopolysaccharide in a chronic-persistent regimen, starting at a dose of 35 μg/100 g body weight for 7 days until reaching a final concentration of 250 μg/100 g and a daily oral administration of β-Caryophyllene at a dose of 10 mg/kg. The effect of β-Caryophyllene on taste perception, inflammatory biomarkers, RAS key-elements, CB2 expression and physiological parameters was evaluated. Results: Data indicate that β-Caryophyllene attenuates systemic inflammation by decreasing IL-1β and IL-6 and increasing ACE2 enzymatic activity in lingual tissue. Also, it was shown that the sesquiterpene reduced taste cell apoptosis and improved sucrose preference, suggesting a feasible restoration of taste dysfunction. Conclusions: These findings demonstrate that β-Caryophyllene could be a potential candidate for treating dysgeusia due to its putative anti-inflammatory and angiotensinergic effects.