Beta-Caryophyllene (BCP) Modulating the Endocannabinoid System and PPARγ to Combat Metabolic Dysregulation: A Narrative Review.

Rahmah S.; Aisyah T.; Meiliana A.; Khairinisa M.; Pratiwi A. · Therapeutics and clinical risk management · 2026

**Background & Methods** This is a narrative review synthesizing current research on beta-caryophyllene (BCP), a naturally occurring compound found in spices like black pepper and cloves, as a therapeutic agent for metabolic diseases. The review comprehensively examines BCP's molecular mechanisms in treating obesity, type 2 diabetes mellitus, metabolic syndrome, and dyslipidemia through modulation of the endocannabinoid system and PPAR-γ receptors. **Key Findings** • BCP activates the AMPK/SIRT1 signaling pathways and inhibits HMG-CoA reductase, producing lipid-lowering and insulin-sensitizing effects that address core metabolic dysfunction including impaired insulin signaling and glucose homeostasis dysregulation. • Animal studies demonstrate that BCP reduces oxidative stress and systemic inflammation by decreasing pro-inflammatory cytokines (TNF-α and IL-6) while improving expression of adiponectin and leptin, markers associated with metabolic health. • BCP acts as a dual modulator of both the endocannabinoid system and PPAR-γ receptors, either directly or indirectly, providing multiple pathways for addressing chronic low-grade inflammation and mitochondrial dysfunction characteristic of metabolic diseases. **Dosage & Administration** Not reported. The review does not specify clinical dosing regimens, routes of administration, or therapeutic doses for human use. BCP is noted as naturally available in dietary sources such as black pepper and cloves. **Safety & Adverse Effects** BCP is described as possessing a favorable safety profile with fewer side effects compared to traditional pharmaceutical agents for metabolic diseases. No specific adverse effects are detailed in the abstract, though the compound is characterized as generally well-tolerated. **Evidence Quality** This narrative review is limited to preclinical evidence, primarily from animal studies and cellular models. A significant translational limitation identified is BCP's extensive first-pass hepatic metabolism, which reduces bioavailability. The authors emphasize the need for advanced delivery systems such as self-emulsifying drug delivery systems (SEDDS) to overcome pharmacokinetic barriers. The review acknowledges the absence of clinical trials in humans and calls for further investigation before BCP can be recommended as a complementary metabolic therapy. The novelty of integrating pharmacodynamics with pharmacokinetic limitations provides balanced perspective, though human clinical evidence remains lacking.

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