Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum

Song, Yunjeong; Seo, Sowoon; Lamichhane, Santosh; Seo, Jooyeok; Hong, Jin Tae; Jin, Hongzhe; Yun, Jaesuk

doi:10.1016/j.phymed.2021.153474

Cited by 45 publications

(17 citation statements)

References 40 publications

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“…Limonene, a common monoterpene found as major component of the active complex of the genus Citrus [15], has been shown to exert anxiolytic, antinociceptive, antioxidant, and anti-inflammatory activity [16][17][18][19][20], as well as to display a protective effect against metabolic syndromes and gastrointestinal and respiratory tract diseases [21,22]. Interestingly, limonene has been suggested to act on the central nervous system, affecting the expression of adenylate cyclase 1 [15], which has been demonstrated to regulate cAMP levels.…”

Section: Introductionmentioning

confidence: 99%

The Antioxidant Activity of Limonene Counteracts Neurotoxicity Triggered byAβ1-42 Oligomers in Primary Cortical Neurons

et al. 2021

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Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer’s disease (AD). In the present study, we tested the neuroprotective effect of limonene, one of the main components of the genus Citrus, against the neurotoxicity elicited by Aβ1-42 oligomers, currently considered a triggering factor in AD. To this aim, we assessed the acetylcholinesterase activity by Ellman’s colorimetric method, the mitochondrial dehydrogenase activity by MTT assay, the nuclear morphology by Hoechst 33258, the generation of reactive oxygen species (ROS) by DCFH-DA fluorescent dye, and the electrophysiological activity of KV3.4 potassium channel subunits by patch-clamp electrophysiology. Interestingly, the monoterpene limonene showed a specific activity against acetylcholinesterase with an IC50 almost comparable to that of galantamine, used as positive control. Moreover, at the concentration of 10 µg/mL, limonene counteracted the increase of ROS production triggered by Aβ1-42 oligomers, thus preventing the upregulation of KV3.4 activity. This, in turn, prevented cell death in primary cortical neurons, showing an interesting neuroprotective profile against Aβ1-42-induced toxicity. Collectively, the present results showed that the antioxidant properties of the main component of the genus Citrus, limonene, may be useful to prevent neuronal suffering induced by Aβ1-42 oligomers preventing the hyperactivity of KV3.4.

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Section: Introductionmentioning

confidence: 99%

The Antioxidant Activity of Limonene Counteracts Neurotoxicity Triggered byAβ1-42 Oligomers in Primary Cortical Neurons

et al. 2021

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“…Limonene is another component present in both EOs, in this case, a study demonstrate that this component can inhibit anxiety-related behavior through A2A receptor-mediated regulation of DAergic and GABAergic neuronal activity 37 . Besides it is possible that terpenes such as geranial and neral present in L. citriodora, also exert anxiolytic action 38 .…”

Section: Discussionmentioning

confidence: 88%

Anxiolytic-like Effect of Essential Oils Extracted from Lippia alba and Lippia citriodora

Alvarado-García¹,

Soto-Vásquez²,

Rosales-Cerquin³

et al. 2021

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“…Nevertheless, other components present in the L. chequen EOs, such as limonene and linalool may exert an anxiolytic effect similar to that seen with diazepam. In the case of limonene, this monoterpene enhances A2A receptor activation and, consequently, induces GABA release and anti-anxiety activity 25 . Meanwhile linalool, one of the most investigated odorant molecules, has an antagonistic action on glutamatergic receptors such as N-methyl-D-aspartate receptors (NMDARs) which may explain its sedative effect 47,48 .…”

Section: Discussionmentioning

confidence: 99%

“…Its leaves and twigs are traditionally used for the treatment of gastrointestinal and respiratory disorders, post-parturition infections, insomnia and anxiety 22 . Luma chequen essential oil is marketed and use in Peru for calming and balancing emotions due to their components such as linalool, limonene among others with anxiolytic properties [23][24][25] . Thus, the present investigation was conducted to evaluate whether aromatherapy based on Luma chequen essential oil can reduce anxiety levels.…”

Section: Introductionmentioning

confidence: 99%

Anxiolytic-like Effect of Luma chequen Essential Oil: A Pilot Study

Alvarado-García¹,

Soto-Vásquez²,

Rosales-Cerquin³

et al. 2021

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Introduction: Essential oils are complex substances used widely extended in the form of aromatherapy or phytotherapy, some of them as agents to relieve anxiety and stress. In this sense this study was conducted to examine the anxiolytic-like effect of Luma chequen essential oil. Methods: The essential oil was extracted by steam distillation and the chemical composition was investigated by Gas chromatography with flame-ionization detection (GC-FID) and Gas chromatography-mass spectrometry (GC-MS). Moreover, a randomized, double blind, placebo-controlled trial was conducted, where 48 participants were divided into two groups, comprising a control group (CG) treated with placebo, and an experimental group (EG) treated with aromatherapy based on Luma chequen essential oil. The anxiety index was evaluated by State-Trait Anxiety Inventory (STAI). Measures were taken at two times: pretest and posttest. Results: The chemical analysis showed that α-pinene was the main component (56.5%). State and Trait anxiety scores showed a decrease in posttest study phase in comparison with pretest in experimental group compared to placebo (p<0.005 for state anxiety and p<0.05 for trait anxiety). Cohen`s d score was 0.84 in State anxiety, while it was 0.52 for Trait anxiety. Percentages of change showed reductions of anxiety variable ranging between 14.94% for State anxiety and 13.60% for Trait anxiety. Conclusions: These results suggest that aromatherapy based on essential oil of Luma chequen was moderately effective in improving anxiety.

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Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum

Cited by 45 publications

References 40 publications

The Antioxidant Activity of Limonene Counteracts Neurotoxicity Triggered byAβ1-42 Oligomers in Primary Cortical Neurons

The Antioxidant Activity of Limonene Counteracts Neurotoxicity Triggered byAβ1-42 Oligomers in Primary Cortical Neurons

Anxiolytic-like Effect of Essential Oils Extracted from Lippia alba and Lippia citriodora

Anxiolytic-like Effect of Luma chequen Essential Oil: A Pilot Study

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