“Recent advances in cannabinoid-based therapies identified the natural CB2 receptor agonist β-caryophyllene (BCP) as a promising anti-inflammatory and neuroprotective agent. To further explore its therapeutic potential on the management of neurodegenerative disorders, in the present study we investigated the ability of BCP to prevent neuroinflammation and promote neuroprotection by using both in vitro and ex vivo models of β-amyloid induced neurotoxicity.
Our data showed that BCP significantly protected human microglial HMC3 cells from Aβ25-35-induced cytotoxicity, reducing the release of pro-inflammatory cytokines (TNF-α, IL-6) while enhancing IL-10 secretion. These effects were associated with a reduced activation of the NF-κB pathway, which emerged as a central mediator of BCP action.
Notably, the use of CB2R- or PPARγ-selective antagonists revealed that the observed NF-κB inhibition by BCP may involve the coordinated activation of both canonical (e.g., CB2R) and non-canonical (e.g., PPARγ) receptors. Moreover, BCP restored the expression of SIRT1, PGC-1α, and BDNF, indicating the involvement of neurotrophic pathways.
Clear neuroprotective properties for BCP have been highlighted in Aβ1-42-treated brain slice preparations, where BCP demonstrated the rescue of both the amyloid-dependent depression of BDNF expression and long-term synaptic potentiation (LTP) impairment.
Overall, our results suggest that BCP constitutes an attractive natural molecule for the treatment of Aβ-induced neuroinflammation and synaptic dysfunction, warranting further exploration for its clinical application.”
https://pubmed.ncbi.nlm.nih.gov/40649806/
“In conclusion, the results of our study suggest a pleiotropic mechanism of action for the development of BCP neuroprotective effects in relation to amyloid-induced neuroinflammation and synaptic impairment, encouraging further investigations into an in vivo model of amyloid-dependent cognitive damage to clarify the exact mechanism of action of BCP and confirm whether this natural molecule may represent a novel option for the treatment of NDDs.
Furthermore, the potent anti-inflammatory effects exerted by BCP through the interaction of CB2 and PPARγ receptors support the therapeutic potential of BCP in a broad range of conditions, including neurodegenerative and metabolic diseases, neuropathic pain, and cancer. Taking into consideration the safety of BCP in humans, dietary use, and its efficacy in various experimental models of disease, BCP may be further explored as co-supplementary drug in experimental studies.”
https://www.mdpi.com/1422-0067/26/13/6027
“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934
“Beta-caryophyllene is a dietary cannabinoid.” https://www.ncbi.nlm.nih.gov/pubmed/18574142