caryophyllene and Cognitive-Dysfunction

Aspartame (ASP) is a common sweetener, but studies show it can harm the nervous system, causing learning and memory deficits. β-caryophyllene (BCP), a natural compound found in foods, including bread, coffee, alcoholic beverages, and spices, has already described as a neuroprotector agent. Remarkably, ASP and BCP are commonly consumed, including in the same meal. Therefore, considering that (a) the BCP displays plenty of beneficial effects; (b) the ASP toxicity; and (c) that they can be consumed in the same meal, this study sought to investigate if the BCP would mitigate the memory impairment induced by ASP in rats and investigate the involvement of the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrKB) signaling pathway and acetylcholinesterase (AChE) activity. Young male Wistar rats received ASP (75 mg/kg; i.g.) and/or BCP (100 mg/kg; i.p.) once daily, for 14 days. At the end of the treatment, the animals were evaluated in the open field and object recognition tests. The cerebral cortex and hippocampus samples were collected for biochemical and molecular analyses. Results showed that the BCP effectively protected against the cognitive damage caused by ASP in short and long-term memories. In addition, BCP mitigated the increase in AChE activity caused by ASP. Molecular insights revealed augmented BDNF and TrKB levels in the hippocampus of rats treated with BCP, indicating greater activation of this pathway. In conclusion, BCP protected against ASP-induced memory impairment. AChE activity and the BDNF/TrkB signaling pathway seem to be potential targets of BCP modulatory role in this study.

Topics: Acetylcholinesterase; Animals; Aspartame; Brain-Derived Neurotrophic Factor; Cognitive Dysfunction; Hippocampus; Male; Memory Disorders; Rats; Rats, Wistar; Receptor, trkB; Signal Transduction; Tropomyosin

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.. In the present study, we evaluated the effects of β-caryophyllene against animal models of dementia whose etiology mimicked neuro-inflammation and aging.. Two doses (50 and 100 mg/kg of body weight) of β-caryophyllene given orally were tested against AlCl. 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.. 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.

Topics: Aging; Aluminum Chloride; Animals; Cognitive Dysfunction; Dementia; Disease Models, Animal; Galactose; Hippocampus; Lipid Peroxidation; Male; Maze Learning; Mitochondrial Diseases; Neuroinflammatory Diseases; Neuroprotective Agents; Oxidative Stress; Polycyclic Sesquiterpenes; Rats; Rats, Sprague-Dawley

Topics: Age Factors; Animals; Cannabinoids; Cognitive Dysfunction; Cytokines; Male; Memory, Short-Term; Mice; Neuroimmunomodulation; Polycyclic Sesquiterpenes; Receptor, Cannabinoid, CB2