β-Caryophyllene (BCP) is a naturally occurring sesquiterpene found in numerous plant species, including Cannabis sativa. BCP has shown a high safety profile and a wide range of biological functions, including beneficial effects in neurodegenerative and inflammatory diseases. Here, we used behavioral, pharmacological, and in-silico docking analyses to investigate the effects and mechanism of action of BCP in Fragile X Syndrome (FXS), the most common inherited cause of Autism Spectrum Disorder (ASD) and intellectual disability. To this aim, we used the recently validated Fmr1-Δexon 8 rat model of FXS, that is also a genetic rat model of ASD. Acute and repeated oral administration of BCP rescued the cognitive deficits displayed by Fmr1-Δexon 8 rats, without inducing tolerance after repeated administration. These beneficial effects were mediated by activation of hippocampal peroxisome proliferator-activated receptors (PPARs) α and γ, and were mimicked by the PPARα agonist Fenofibrate and the PPARγ agonist Pioglitazone. Conversely, CB2 cannabinoid receptors were not involved. Docking analyses further confirmed the ability of BCP to bind rat PPARs. Together, our findings demonstrate that hippocampal PPARs α and γ play a role in the cognitive deficits observed in a rat model of FXS, and provide first preclinical evidence about the efficacy and mechanism of action of BCP in neurodevelopmental disorders.

Role of peroxisome proliferator-activated receptors α and γ in mediating the beneficial effects of β-caryophyllene in a rat model of fragile X syndrome / Rava, Alessandro; Buzzelli, Valeria; Feo, Alessandro; Ascone, Fabrizio; Di Trapano, Melania; Schiavi, Sara; Carbone, Emilia; Pasquadibisceglie, Andrea; Polticelli, Fabio; Manduca, Antonia; Trezza, Viviana. - In: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY. - ISSN 0278-5846. - 136:(2024). [10.1016/j.pnpbp.2024.111234]

Role of peroxisome proliferator-activated receptors α and γ in mediating the beneficial effects of β-caryophyllene in a rat model of fragile X syndrome

Rava, Alessandro;Buzzelli, Valeria;Manduca, Antonia;Trezza, Viviana
2024

Abstract

β-Caryophyllene (BCP) is a naturally occurring sesquiterpene found in numerous plant species, including Cannabis sativa. BCP has shown a high safety profile and a wide range of biological functions, including beneficial effects in neurodegenerative and inflammatory diseases. Here, we used behavioral, pharmacological, and in-silico docking analyses to investigate the effects and mechanism of action of BCP in Fragile X Syndrome (FXS), the most common inherited cause of Autism Spectrum Disorder (ASD) and intellectual disability. To this aim, we used the recently validated Fmr1-Δexon 8 rat model of FXS, that is also a genetic rat model of ASD. Acute and repeated oral administration of BCP rescued the cognitive deficits displayed by Fmr1-Δexon 8 rats, without inducing tolerance after repeated administration. These beneficial effects were mediated by activation of hippocampal peroxisome proliferator-activated receptors (PPARs) α and γ, and were mimicked by the PPARα agonist Fenofibrate and the PPARγ agonist Pioglitazone. Conversely, CB2 cannabinoid receptors were not involved. Docking analyses further confirmed the ability of BCP to bind rat PPARs. Together, our findings demonstrate that hippocampal PPARs α and γ play a role in the cognitive deficits observed in a rat model of FXS, and provide first preclinical evidence about the efficacy and mechanism of action of BCP in neurodevelopmental disorders.
2024
Cognitive performance; Fragile X syndrome; Peroxisome proliferator-activated receptors; Rat model; β-Caryophyllene
01 Pubblicazione su rivista::01a Articolo in rivista
Role of peroxisome proliferator-activated receptors α and γ in mediating the beneficial effects of β-caryophyllene in a rat model of fragile X syndrome / Rava, Alessandro; Buzzelli, Valeria; Feo, Alessandro; Ascone, Fabrizio; Di Trapano, Melania; Schiavi, Sara; Carbone, Emilia; Pasquadibisceglie, Andrea; Polticelli, Fabio; Manduca, Antonia; Trezza, Viviana. - In: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY. - ISSN 0278-5846. - 136:(2024). [10.1016/j.pnpbp.2024.111234]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1730808
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? ND
social impact