Title:Beta-Caryophyllene, a CB2R Selective Agonist, Protects Against Cognitive Impairment Caused by Neuro-inflammation and Not in Dementia Due to Ageing Induced by Mitochondrial Dysfunction
Volume: 20
Issue: 10
Author(s): Urja Kanojia, Shrikant Gyaneshwar Chaturbhuj, Runali Sankhe, Maushami Das, Raviteja Surubhotla, Nandakumar Krishnadas, Karthik Gourishetti, Pawan Ganesh Nayak and Anoop Kishore*
Affiliation:
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka,India
Keywords:
β-caryophyllene, cognitive impairment, D-galactose, doxorubicin, chemobrain, aluminium chloride, cannabinoid 2
receptor.
Abstract:
Background: Dementia is a neurodegenerative disorder majorly evidenced by cognitive
impairment. Although there are many types of dementia, the common underlying etiological factors
in all the types are neuro-inflammation or aging induced apoptosis. β-caryophyllene, a cannabinoid
type-2 receptor agonist, has been reported to have promising neuroprotective effects in cerebral
ischemia and neuro-inflammation.
Objective: In the present study, we evaluated the effects of β-caryophyllene against animal models
of dementia whose etiology mimicked neuro-inflammation and aging.
Methods: Two doses (50 and 100 mg/kg of body weight) of β-caryophyllene given orally were tested
against AlCl3-induced dementia in male Sprague Dawley (SD) rats using the Morris water maze
test. Subsequently, the effect of the drug was assessed for episodic memory in female SD rats using
novel object recognition task in doxorubicin-induced neuro-inflammation and chemobrain model.
Moreover, its effects were evaluated in D-galactose-induced mitochondrial dysfunction leading to
dementia.
Results: β-caryophyllene, at both doses, showed significant improvement in memory when assessed
using parameters like target quadrant entries, escape latency and path efficiency in the Morris
water maze test for spatial memory. In the doxorubicin-induced chemobrain model, β-caryophyllene
at 100 mg/kg significantly elevated acetylcholinesterase and catalase levels and lowered lipid
peroxidation compared to the disease control. In the novel object recognition task, β-caryophyllene
at 100 mg/kg significantly improved recognition index and discrimination index in the treated animals
compared to the disease control, with a significant increase in catalase and a decrease in lipid
peroxidation in both hippocampus and frontal cortex. However, in the D-galactose-induced mitochondrial
dysfunction model, β-caryophyllene failed to show positive effects when spatial memory
was assessed. It also failed to improve D-galactose-induced diminished mitochondrial complex I
and II activities.
Conclusion: Hence, we conclude that β-caryophyllene at 100 mg/kg protects against dementia induced
by neuro-inflammation with no effect on neuronal aging induced by mitochondrial dysfunction.
