Antidepressant-Like Effect of Essential Oils From <i>Citrus reticulata</i> in Reserpine-Induced Depressive Mouse

Tang, Minghui; Ai, Yong; Zhu, Shiqiang; Song, Ning; Xu, Xiaodong; Liang, Leyi; Rong, Baoshan; Zheng, Xiao; Zhang, Lanyue; He, Tinggang

doi:10.1177/1934578x221093916

Cited by 6 publications

(6 citation statements)

References 36 publications

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“…The duration of immobility markedly decreased in animals administered a single dose of CBEO (25 mg/kg), indicating a rapid antidepressant effect. These results align with those of previous studies ( Tang et al, 2022 ; Tsai et al, 2023 ), although those studies required a longer treatment duration (one to six weeks) and higher doses (100–500 mg/kg for oral administration), suggesting an outstanding advantage of intranasal administration. Compared with other routes, intranasal delivery has been prominent in drug development in recent years owing to its rapid effects and high bioavailability by crossing the blood–brain barrier directly and avoiding the first-pass effect ( Shringarpure et al, 2021 ).…”

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

“…Pharmaceutical studies have shown that CBEO and its components have antioxidant, anti-inflammatory, anticancer, antibacterial, and antifungal properties ( Dosoky and Setzer, 2018 ). According to a previous study, CBEO improves reserpine-induced depressive behavior, possibly by regulating the expression of brain-derived neurotrophic factors, glucocorticoid receptors, and 5-hydroxytryptamine-1A receptors ( Tang et al, 2022 ). Another study revealed that CBEO possessed antidepressant activity by modulating the gut microbiota ( Tsai et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

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Antidepressant and anxiolytic potential of Citrus reticulata Blanco essential oil: a network pharmacology and animal model study

Khanh Nguyen,

Kwon,

Kim

et al. 2024

Front. Pharmacol.

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Background:Citrus reticulata Blanco essential oil (CBEO) has attracted increasing attention as a potential treatment for depression and anxiety in recent years. However, there is limited evidence regarding the active compounds responsible for its therapeutic effects. In addition, substantial amounts of CBEO and prolonged therapy are often required. This study aims to investigate the rapid acting antidepressant and anxiolytic effects of CBEO, identify the underlying composition as well as optimize its dosage and duration.Methods:CBEO composition was determined using gas chromatography–mass spectrometry (GC–MS), and the corresponding targets were obtained from the SwissTargetPrediction database. Depression-related targets were collected from DisGeNET, GeneCards, Therapeutic Target Database, and Online Mendelian Inheritance in Man. Subsequently, the overlap between CBEO and depression targets was utilized to build a network diagram depicting the relationship between the active ingredients and targets using Cytoscape software. The STRING database facilitated the construction of a protein–protein interaction network, and the Ma’ayan Laboratory Enrichment tool was employed for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Wiki pathway analyses. Molecular docking was conducted using AutoDock Vina and Discovery Studio Visualizer. Topological analysis predicted the main antidepressant active ingredients in CBEO. A mixture of these compounds was prepared based on their relative GC–MS ratios. Tail suspension test, elevated plus maze, corticosterone-induced PC12 cells, and lipopolysaccharide (LPS)-induced BV2 cells were used to validate the antidepressant and anxiolytic potential of CBEO and CBEO’s main bioactive constituents.Results:CBEO contains 18 components that target 121 proteins. We identified 595 targets associated with depression; among them, 29 targets were located between essential oils and depression. Topological results revealed that linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol were the major active compounds of CBEO in the management of depression. GO analysis identified G protein-coupled opioid receptor activity, phospholipase C-activating G protein-coupled receptor, and neuron projections that were mostly related to molecular functions, cellular components, and biological processes. Neuroactive ligand-receptor interactions, chemical carcinogenesis, and calcium signaling pathways were the major pathways identified in KEGG analysis. Molecular docking showed that the main bioactive ingredients of CBEO had favorable binding affinities for Protein-Protein Interaction’s hub proteins, including OPRM1, PTGS2, ESR1, SLC6A4, DRD2, and NR3C1. These five compounds were then mixed at 0.8:5:0.6:2:1 (w/w) ratio to form a CBEO antidepressant active compound mixture. An acute intranasal treatment of CBEO (25 mg/kg) only demonstrated an antidepressant effect, whereas the main bioactive compounds combination (12.5 mg/kg) illustrated both antidepressant and anxiolytic effects in mice. Linalool, p-cymene, and terpinene-4-ol exhibited neuroprotective and anti-neuroinflammation in the in vitro study, while these effects were not observed for α-terpinene and α-terpineol.Conclusion:Linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol cymene might be mainly contributing to CBEO’s antidepressant effect by regulating neuroactive ligand-receptor interaction, neuron projection, and receptor signaling pathway. A mixture of these compounds showed rapid antidepressant potential via intranasal administration, which was comparable to that of CBEO. The mixture also exhibited an anxiolytic effect while not seen in CBEO.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Antidepressant and anxiolytic potential of Citrus reticulata Blanco essential oil: a network pharmacology and animal model study

Khanh Nguyen,

Kwon,

Kim

et al. 2024

Front. Pharmacol.

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“…Improvements in the neuroendocrine, neurotrophic, and monoaminergic systems are related to the antidepressant effects of limonene in mice [ 131 ]. A recent study demonstrated that C. reticulata essential oils (CREOs), which contain d -limonene as the main component, can serve as a potential therapeutic drug and food supplement against depression [ 132 ].…”

Section: Resultsmentioning

confidence: 99%

Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut–Brain Axis

Liaqat

Parveen

Kim

2022

IJMS

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Modern neurological approaches enable detailed studies on the pathophysiology and treatment of depression. An imbalance in the microbiota–gut–brain axis contributes to the pathogenesis of depression. This extensive review aimed to elucidate the antidepressive effects of brain-derived neurotrophic factor (BDNF)-targeting therapeutic natural products and their derivatives on the gut–brain axis. This information could facilitate the development of novel antidepressant drugs. BDNF is crucial for neuronal genesis, growth, differentiation, survival, plasticity, and synaptic transmission. Signaling via BDNF and its receptor tropomyosin receptor kinase B (TrkB) plays a vital role in the etiopathogenesis of depression and the therapeutic mechanism of antidepressants. This comprehensive review provides information to researchers and scientists for the identification of novel therapeutic approaches for neuropsychiatric disorders, especially depression and stress. Future research should aim to determine the possible causative role of BDNF-TrkB in the gut–brain axis in depression, which will require further animal and clinical research as well as the development of analytical approaches.

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“…Value of p threshold = 0.05, k > 20 (number of voxels per cluster). Frontiers Nutrition 09 frontiersin.org models (14, 16,17,36,37). We can hypothesize that under acute stress our formulation and/or dosing may have not been sufficient to reduce significantly the emotional reactivity of FS animals.…”

Section: Behavioral Outcomes Of Chronic Exposure To the Functional In...mentioning

confidence: 99%

Exposure to a sensory functional ingredient in the pig model modulates the blood-oxygen-level dependent brain responses to food odor and acute stress during pharmacological MRI in the frontostriatal and limbic circuits

Briard¹,

Serrand²,

Dahirel³

et al. 2023

Front. Nutr.

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IntroductionIn the present study, we examined the effects of a supplementation with a sensory functional ingredient (FI, D16729, Phodé, France) containing vanillin, furaneol, diacetyl and a mixture of aromatic fatty acids on the behavioural and brain responses of juvenile pigs to acute stress.MethodsTwenty-four pigs were fed from weaning with a standard granulated feed supplemented with the functional ingredient D16729 (FS animals, N = 12) or a control formulation (CT animals, N = 12). After a feed transition (10 days after weaning), the effects of FI were investigated on eating behaviour during two-choice feed preference tests. Emotional reactivity to acute stress was then investigated during openfield (OF), novel suddenly moving object (NSO), and contention tests. Brain responses to the FI and the two different feeds’ odour, as well as to an acute pharmacological stressor (injection of Synacthen®) were finally investigated with functional magnetic resonance imaging (fMRI).ResultsFS animals tended to spend more time above the functional feed (p = 0.06) and spent significantly more time at the periphery of the arena during NSO (p < 0.05). Their latency to contact the novel object was longer and they spent less time exploring the object compared to CT animals (p < 0.05 for both). Frontostriatal and limbic responses to the FI were influenced by previous exposure to FI, with higher activation in FS animals exposed to the FI feed odor compared to CT animals exposed to a similarly familiar feed odor without FI. The pharmacological acute stress provoked significant brain activations in the prefrontal and thalamic areas, which were alleviated in FS animals that also showed more activity in the nucleus accumbens. Finally, the acute exposure to FI in naive animals modulated their brain responses to acute pharmacological stress.DiscussionOverall, these results showed how previous habituation to the FI can modulate the brain areas involved in food pleasure and motivation while alleviating the brain responses to acute stress.

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Antidepressant-Like Effect of Essential Oils From Citrus reticulata in Reserpine-Induced Depressive Mouse

Cited by 6 publications

References 36 publications

Antidepressant and anxiolytic potential of Citrus reticulata Blanco essential oil: a network pharmacology and animal model study

Antidepressant and anxiolytic potential of Citrus reticulata Blanco essential oil: a network pharmacology and animal model study

Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut–Brain Axis

Exposure to a sensory functional ingredient in the pig model modulates the blood-oxygen-level dependent brain responses to food odor and acute stress during pharmacological MRI in the frontostriatal and limbic circuits

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