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

**Authors:** Sofía Cecilia López-Salido, Hugo Alejandro Espinoza-Gutiérrez, Mario Eduardo Flores-Soto, Alma Hortensia Martínez-Preciado, Juan Manuel Viveros-Paredes

PMC · DOI: 10.3390/biomedicines13102514 · Biomedicines · 2025-10-15

## TL;DR

This study shows that β-Caryophyllene may help reduce inflammation and restore taste function in mice with dysgeusia.

## Contribution

The study introduces β-Caryophyllene as a novel modulator of the Renin–Angiotensin System for treating dysgeusia.

## Key findings

- β-Caryophyllene reduced systemic inflammation by decreasing IL-1β and IL-6 levels.
- It increased ACE2 activity in lingual tissue and improved sucrose preference in mice.
- The compound reduced taste cell apoptosis and showed angiotensinergic effects.

## Abstract

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.

## Linked entities

- **Proteins:** CNR2 (cannabinoid receptor 2), ACE2 (angiotensin converting enzyme 2)
- **Chemicals:** β-Caryophyllene (PubChem CID 5281515), IL-6 (PubChem CID 165368475)

## Full-text entities

- **Genes:** Cnr2 (cannabinoid receptor 2) [NCBI Gene 12802] {aka CB-2, CB2, CB2-R}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Ace2 (angiotensin converting enzyme 2) [NCBI Gene 70008] {aka 2010305L05Rik}
- **Diseases:** taste disorder (MESH:D013651), Inflammation (MESH:D007249), Dysgeusia (MESH:D004408), diseases (MESH:D004194)
- **Chemicals:** lipopolysaccharide (MESH:D008070), sesquiterpene (MESH:D012717), sucrose (MESH:D013395), beta-Caryophyllene (MESH:C024714)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** /c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12561559/full.md

## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12561559/full.md

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Source: https://tomesphere.com/paper/PMC12561559