Angiotensinergic effect of β-Caryophyllene on Lipopolysaccharide- induced systemic inflammation

• Published in: Biochemical and biophysical research communications Vol. 719; p. 150081
• Main Authors: Espinoza-Gutiérrez, Hugo Alejandro, López-Salido, Sofía Cecilia, Flores-Soto, Mario Eduardo, Tejeda-Martínez, Aldo Rafael, Chaparro-Huerta, Veronica, Viveros-Paredes, Juan Manuel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.07.2024
• Subjects: Angiotensin I - metabolism; Animals; Anti-Inflammatory Agents - pharmacology; blood pressure; blood serum; Chronic stress; Corticosterone; cytokines; Endocannabinoid system; inflammation; Inflammation - drug therapy; Inflammation - metabolism; Lipopolysaccharides; Male; Mice; oral administration; Peptide Fragments - metabolism; peptidyl-dipeptidase A; phytochemicals; Polycyclic Sesquiterpenes - pharmacology; Pro/anti-inflammatory cytokines; renin; Renin-angiotensin system; Renin-Angiotensin System - drug effects; Sesquiterpenes - pharmacology; sesquiterpenoids; β-Caryophyllene; β-Caryophyllene; Chronic stress; Endocannabinoid system; Pro/anti-inflammatory cytokines; Renin-angiotensin system; Corticosterone
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.150081

Renin-Angiotensin System (RAS) is a peptidergic system, canonically known for its role in blood pressure regulation. Furthermore, a non-canonical RAS regulates pathophysiological phenomena, such as inflammation since it consists of two main axes: the pro-inflammatory renin/(pro)renin receptor ((P)RR) axis, and the anti-inflammatory angiotensin-converting enzyme 2 (ACE2)/Angiotensin-(1–7) (Ang-(1–7))/Mas Receptor (MasR) axis. Few phytochemicals have shown to exert angiotensinergic and anti-inflammatory effects through some of these axes; nevertheless, anti-inflammatory drugs, such as phytocannabinoids have not been studied regarding this subject. Among phytocannabinoids, β-Caryophyllene stands out as a dietary phytocannabinoid with antiphlogistic activity that possess a unique sesquiterpenoid structure. Although its cannabinergic effect has been studied, its angiotensinergic effect reminds underexplored. This study aims to explore the angiotensinergic effect of β-Caryophyllene on inflammation and stress at a systemic level. After intranasal Lipopolysaccharide (LPS) installation and oral treatment with β-Caryophyllene, the concentration and activity of key RAS elements in the serum, such as Renin, ACE2 and Ang-(1–7), along with the stress hormone corticosterone and pro/anti-inflammatory cytokines, were measured in mice serum. The results show that β-Caryophyllene treatment modified RAS levels by increasing Renin and Ang-(1–7), alongside the reduction of pro-inflammatory cytokines and corticosterone levels. These results indicate that β-Caryophyllene exhibits angiotensinergic activity in favor of anti-inflammation. [Display omitted] •Angiotensinergic effect of β-Caryophyllene is characterized by the increase of serum Renin and Angiotensin-(1–7).•β-Caryophyllene reduces serum pro-inflammatory cytokines as well as the stress hormone corticosterone.•The increase of Angiotensin-(1–7) is positively associated with the increase of IL-10.•β-Caryophyllene does not modify the enzymatic activity of soluble Angiotensin-Converting Enzyme 2.