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

Kanojia, Urja and Chaturbhuj, Shrikant Gyaneshwar and Sankhe, Runali and Das, Maushami and Surubhotla, Raviteja and Krishnadas, Nandakumar and Gourishetti, Karthik and Nayak, Pawan G and Kishore, Anoop (2021) 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. CNS and Neurological Disorders - Drug Targets, 20 (10). pp. 963-974. ISSN 18715273

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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.

Item Type: Article
Uncontrolled Keywords: β-caryophyllene; cognitive impairment; D-galactose; doxorubicin; chemobrain; aluminium chloride; cannabinoid 2 receptor
Subjects: Medicine > KMC Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 15 Feb 2022 05:48
Last Modified: 15 Feb 2022 05:48
URI: http://eprints.manipal.edu/id/eprint/158292

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