Pharmacological, Molecular Mechanisms, and Therapeutic Potential of β-Caryophyllene and β-Caryophyllene-Rich Plants in Liver Diseases

FASEB J. 2026 Jan 15;40(1):e71344. doi: 10.1096/fj.202502436R.

Abstract

β-caryophyllene, a bicyclic sesquiterpene widely abundant in various plant essential oils, has garnered growing attention for its potential biological effects and therapeutic benefits in liver diseases. This review systematically evaluates preclinical evidence on the pharmacological properties of BCP with emphasis on its hepatoprotective effects primarily through its anti-inflammatory, antioxidant, antifibrotic, and immunomodulatory actions. BCP is classified as a dietary cannabinoid due to its ability to activate cannabinoid type 2 receptors in the endocannabinoid system and thereby influence key cellular signaling pathways involved in lipid metabolism and tissue remodeling. Emerging studies also highlight BCP interaction with PPAR nuclear receptor and AMPK signaling, further corroborating its role in regulating lipid homeostasis. In the present review, we compile, summarize, and critically analyze findings from in vitro and in vivo studies on nonalcoholic fatty liver disease, recently termed as metabolic dysfunction-associated fatty liver disease (MAFLD), alcoholic liver disease, and liver fibrosis, highlighting the pharmacological and molecular mechanisms underlying therapeutic effects. These studies consistently demonstrate a reduction in hepatic steatosis, collagen deposition, and hepatocellular markers reflecting a broad spectrum of hepatoprotective effects. Taken together, the pharmacological properties and mechanistic insights place BCP as a promising natural compound with nutraceutical, phytopharmaceutical, or dietary supplement applications for liver diseases. Despite the robust preclinical evidence, clinical validation remains scarce. Therefore, regulatory toxicology and efficacy studies are needed to establish the therapeutic potential of BCP in liver diseases and its integration as a nutraceutical or phytopharmaceutical in the clinical usage.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Lipid Metabolism / drug effects
  • Liver Diseases* / drug therapy
  • Liver Diseases* / metabolism
  • Polycyclic Sesquiterpenes* / pharmacology
  • Polycyclic Sesquiterpenes* / therapeutic use
  • Sesquiterpenes* / pharmacology
  • Sesquiterpenes* / therapeutic use

Substances

  • Polycyclic Sesquiterpenes
  • caryophyllene
  • Sesquiterpenes