CB2 agonist shows promise as immune-modulating feed supplement for cattle

Cannabinoid receptor-2 ligand beta-caryophyllene modulates inflammatory responses of bovine peripheral blood mononuclear cells in vitro.

Scientific reports • • Moderately Relevant
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AI Summary

This study marks the first investigation of beta-caryophyllene (BCP), a CB2 receptor agonist found in cannabis and many other plants, in cattle immune cells. Researchers isolated peripheral blood mononuclear cells from dairy cows and exposed them to BCP at two different concentrations while simulating normal and heat-stress conditions. The results revealed that BCP modulated immune function, though the effects were complex and dose-dependent. At the higher concentration (1 mM), BCP reduced CB2 gene expression and altered inflammatory signaling pathways, including effects on immune-related proteins and genes like NFKB1, TNF-α, and IL-10.

The findings suggest that BCP acts as an immune modulator rather than simply suppressing inflammation. At the higher dose, BCP increased certain inflammatory markers like monocyte-chemoattractant-protein-1 while affecting others, and showed a trend toward lower cAMP levels—an indicator of CB2 activation. Heat stress independently affected immune responses, but BCP's effects remained relatively consistent regardless of temperature conditions. These results are preliminary but encouraging for exploring BCP as a potential feed supplement in livestock to support immune function during stressful conditions.

While this research focuses on cattle rather than humans, it provides important evidence that CB2-targeting compounds can modulate immune responses in practical agricultural settings. The study suggests that BCP's immunomodulatory effects could potentially help livestock cope with environmental stress, which has broader implications for understanding how CB2 agonists work in mammalian immune systems. However, researchers emphasize that further in-vivo studies are needed before BCP can be recommended as a livestock supplement, and the results cannot yet be extrapolated to human cannabis use.

📄 Original Abstract

Beta-caryophyllene (BCP) is an agonist of cannabinoid receptor 2 (CNR2/CB2), exerting mostly anti-inflammatory effects in rodents, but not explored in cattle. Herein we conducted the first reductionist step to examine the effects of in-vitro supplementation of BCP in bovine peripheral blood mononuclear cells (PBMCs) on the inflammatory response under thermoneutral (TN) or heat stress (HS) conditions. We performed this work in two cohorts: in Study 1, PBMC were supplemented with BCP at 1 µM (n = 8), and in Study 2 PBMC from other cows were supplemented with BCP at 1 mM (n = 7). In each study, PBMC from each cow were assigned to controls (CTL) or BCP-supplemented and incubated in TN (38.5 °C) or HS (41.0 °C) conditions. Then, half of the cells from each cow were treated with lipopolysaccharide (LPS), and media were collected for analysis of cytokines/chemokines and cyclic adenosine monophosphate (cAMP) concentrations as indicator of CB2 activation. In addition, RNA and proteins were extracted from plate-adhered monocyte-enriched-PBMCs (MEPs), for gene-expression and proteomics analyses. In each study, the effects of BCP, LPS, HS, and interactions were analyzed. We found in both studies that LPS and BCP (at 1 µM or at 1 mM) lowered CNR2 gene expression in MEPs. At 1 mM, BCP inhibited gene expression of LPS-induced NFKB1, amplified TNFA, and suppressed IL10, and tended to reduce cAMP in medium, possibly indicating CB2 activation. Post-LPS, BCP (1 mM) increased monocyte-chemoattractant-protein-1 and tended to enhance interleukin-1-alpha, beta, and macrophage-inflammatory-protein-1-alpha in medium; while HS increased macrophage-inflammatory-protein-1-beta. Proteomics of LPS-activated MEPs revealed immune-related proteins and canonical pathways enriched by BCP. Overall, BCP supplementation in vitro modulated immune function in PBMC from dairy cows, with similar effects in TN and HS conditions; thus, BCP could be studied as a potential feed supplement in cattle that may induce moderate immune-modulating effects. Further studies should investigate the in vivo effects of BCP on immune function in cattle.

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