Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation

Abstract

(E)-β-caryophyllene (BCP) is a bicyclic sesquiterpene widely distributed in the plant kingdom, where it contributes a unique aroma to essential oils and has a pivotal role in the survival and evolution of higher plants. Recent studies provided evidence for protective roles of BCP in animal cells, highlighting its possible use as a novel therapeutic tool. Experimental results show the ability of BCP to reduce pro-inflammatory mediators such as tumor necrosis factor-alfa (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thus ameliorating chronic pathologies characterized by inflammation and oxidative stress, in particular metabolic and neurological diseases. Through the binding to CB2 cannabinoid receptors and the interaction with members of the family of peroxisome proliferator-activated receptors (PPARs), BCP shows beneficial effects on obesity, non-alcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) liver diseases, diabetes, cardiovascular diseases, pain and other nervous system disorders. This review describes the current knowledge on the biosynthesis and natural sources of BCP, and reviews its role and mechanisms of action in different inflammation-related metabolic and neurologic disorders.

Keywords: (E)-β-caryophyllene; biosynthesis and distribution; cardiovascular disorders; inflammation; metabolic disorders; neurodegenerative diseases; obesity; pain; steatosis; type II diabetes.

Figure 1

Simplified mechanism of the formation of (E)-β-caryophyllene (BCP) from DMAPP and IPP. Abbreviations: DMAPP, dimethylallyl diphosphate; IPP, isopentenyl diphosphate; TPS, terpene synthase. Modified from [36].

Figure 2

Positive effects of BCP on metabolic and neurological disorders. Scheme created with BioRender.com. ↓: reduction; ↑: increase; LDL: Low density lipoproteins; HMG-CoA: Hydroxy methylglutaryl-Coenzyme A; FAS: fatty acid synthase; ATGL: adipose triglyceride lipase; GLUT4: glucose transporter 4.