Beta-caryophyllene alleviates diet-induced neurobehavioral changes in rats: The role of CB2 and PPAR-γ receptors.
Animals
Anti-Inflammatory Agents, Non-Steroidal
/ pharmacology
Diet, High-Fat
/ adverse effects
Fructose
/ toxicity
Male
Maze Learning
/ drug effects
Memory Disorders
/ drug therapy
Obesity
/ drug therapy
Oxidative Stress
/ drug effects
PPAR gamma
/ metabolism
Polycyclic Sesquiterpenes
Rats
Rats, Wistar
Receptor, Cannabinoid, CB2
/ metabolism
Sesquiterpenes
/ pharmacology
Beta-caryophyllene
Cannabinoid receptor 2
High fat/fructose diet
Insulin resistance
PGC-1α
PPAR-γ
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
01
10
2018
revised:
30
10
2018
accepted:
10
11
2018
pubmed:
24
11
2018
medline:
19
4
2019
entrez:
24
11
2018
Statut:
ppublish
Résumé
Insulin resistance (IR) and obesity predispose diseases such as diabetes, cardiovascular and neurodegenerative disorders. Beta-caryophyllene (BCP), a natural sesquiterpene, exerts neuroprotective, anxiolytic and antidepressant effects via its selective agonism to cannabinoid receptor 2 (CB2R). BCP was shown to have an anti-diabetic effect, however, the implication of CB2R is yet to be elucidated. A link between CB2R agonism and PPAR-γ activation has been discussed, but the exact mechanism is not well-defined. This study was designed to examine the role of BCP in improving diet-induced metabolic (insulin resistance), neurobehavioral (anxiety, depression and memory deficit), and neurochemical (oxidative, inflammatory and neurotrophic factor) alterations in the prefrontal cortex of obese rats' brain. The involvement of CB2R and/or PPAR-γ dependent activity was also investigated. Male Wistar rats were fed a high fat/fructose diet (HFFD) for 12 weeks to induce IR and obesity. Rats were treated with BCP for the last 4 weeks. Either CB2R antagonist AM630 or PPAR-γ antagonist BADGE was administered before BCP treatment to study the mechanism of BCP actions. Beta-caryophyllene alleviated HFFD-induced IR, oxidative-stress, neuroinflammation and behavioral changes. The anxiolytic, anti-oxidant and anti-inflammatory effects of BCP were mediated by both PPAR-γ and CB2R. The effects of BCP on glycemic parameters seem to be CB2R-dependent with the non-significant role of PPAR-γ. Furthermore, BCP-evoked antidepressant and memory improvement are likely mediated only via CB2R, mainly by upregulation of PGC-1α and BDNF. This study suggests the potential effect of BCP in treating HFFD-induced metabolic and neurobehavioral alterations. BCP seems to activate PPAR-γ in a ligand-independent manner, via upregulation and activation of PGC-1α. The BCP activation of PPAR--γ seems to be CB2R-dependent.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
Insulin resistance (IR) and obesity predispose diseases such as diabetes, cardiovascular and neurodegenerative disorders. Beta-caryophyllene (BCP), a natural sesquiterpene, exerts neuroprotective, anxiolytic and antidepressant effects via its selective agonism to cannabinoid receptor 2 (CB2R). BCP was shown to have an anti-diabetic effect, however, the implication of CB2R is yet to be elucidated. A link between CB2R agonism and PPAR-γ activation has been discussed, but the exact mechanism is not well-defined. This study was designed to examine the role of BCP in improving diet-induced metabolic (insulin resistance), neurobehavioral (anxiety, depression and memory deficit), and neurochemical (oxidative, inflammatory and neurotrophic factor) alterations in the prefrontal cortex of obese rats' brain. The involvement of CB2R and/or PPAR-γ dependent activity was also investigated.
EXPERIMENTAL APPROACH
METHODS
Male Wistar rats were fed a high fat/fructose diet (HFFD) for 12 weeks to induce IR and obesity. Rats were treated with BCP for the last 4 weeks. Either CB2R antagonist AM630 or PPAR-γ antagonist BADGE was administered before BCP treatment to study the mechanism of BCP actions.
KEY RESULTS
RESULTS
Beta-caryophyllene alleviated HFFD-induced IR, oxidative-stress, neuroinflammation and behavioral changes. The anxiolytic, anti-oxidant and anti-inflammatory effects of BCP were mediated by both PPAR-γ and CB2R. The effects of BCP on glycemic parameters seem to be CB2R-dependent with the non-significant role of PPAR-γ. Furthermore, BCP-evoked antidepressant and memory improvement are likely mediated only via CB2R, mainly by upregulation of PGC-1α and BDNF.
CONCLUSION
CONCLUSIONS
This study suggests the potential effect of BCP in treating HFFD-induced metabolic and neurobehavioral alterations. BCP seems to activate PPAR-γ in a ligand-independent manner, via upregulation and activation of PGC-1α. The BCP activation of PPAR--γ seems to be CB2R-dependent.
Identifiants
pubmed: 30469079
pii: S0753-3322(18)37003-3
doi: 10.1016/j.biopha.2018.11.039
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
PPAR gamma
0
Polycyclic Sesquiterpenes
0
Receptor, Cannabinoid, CB2
0
Sesquiterpenes
0
Fructose
30237-26-4
caryophyllene
BHW853AU9H
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
145-154Informations de copyright
Copyright © 2018. Published by Elsevier Masson SAS.