A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models
Abstract
:1. Introduction
2. Results and Discussion
2.1. Abies sachalinensis
2.2. Acantholippia deserticola
2.3. Achillea umbelata
2.4. Achillea wilhemsii
Essential Oils | Administration | Specie | Anxiety Model | Observed Effect | Motor Activity | Mechanism of Action | Observation | Reference | |
---|---|---|---|---|---|---|---|---|---|
Abies sachalinensis | Inhalation (acute) i.p. (acute) | Mouse | Elevated plus-maze | Anxiolytic-like No effect | Not evaluated | 10-min session DR+ | [12] | ||
Acantholippia deserticola | i.p. | Rat | Elevated plus-maze | Anxiolytic-like? | Decrease | Female only Toxicity? DR+ | [13] | ||
Achillea umbelata | Oral (acute) | Mice | Light/Dark | Anxiolytic-like? | Decrease | Toxicity? DR+ | [14] | ||
Achillea wilhemsii | i.p. (acute) | Rat | Elevated plus-maze | Anxiolytic-like | Decrease? | Not mediated by BDZ Not mediated by opioid receptors | DR+ | [15] | |
Alpinia zerumbet | i.p. (acute) | Mouse | Elevated plus-maze | No effect | Decrease | DR+ | [16] | ||
Inhalation (acute) | Mouse | Elevated plus-maze | Anxiolytic-like | No change | Decrease 5-HTP and fluoxetine induced jumping (5-HT action) | Motor activity evaluated trough rearing DR+ | [17] | ||
Inhalation (3 days) Inhalation (1 day) | Mouse | Elevated plus-maze Light/Dark | Anxiolytic-like No effect | No change No change | DR− | [18] | |||
Inhalation (5–150 min) | Mouse | Elevated plus-maze | Anxiolytic-like | No change | Anxiolytic-like effect is dependent of duration of inhalation (30–120 min) DR+ | [12] | |||
Angelica sinensis | Oral (acute) | Mouse | Elevated plus-maze Light/Dark Stress-induced hyperthermia | Anxiolytic-like Anxiolytic-like Anxiolytic-like | No change | Inverted U curve DR+ | [19] | ||
Oral (acute) | Rat | Social Interaction | Putative Anxiolytic-like | Increase | Inverted U curve DR+ | [19] | |||
Casimiroa pringlei | Oral (acute) | Rat | Elevated plus-maze Holeboard | No effect (compared to control) | No change | Positive effect when compared to caffeine only DR+ | [20] | ||
Celastarus paniculatus | Oral (repeated) | Rat | Elevated plus-maze Vogel | Anxiolytic-like Anxiolytic-like | No change | [21] | |||
Chamaecyparis obtusa | Inhaled (acute) | Mouse | Elevated plus-maze | Anxiolytic-like | Not evaluated | 10-min session DR+ | [22] | ||
Inhaled (repeated) | Rat | Elevated plus-maze | Reversed anxiogenic-like effect of mother separation | Not evaluated | Associated with IL-6 and Ccl2 cytokines reductions | DR− | [23] | ||
Citrus aurantium L. | Oral | Mouse | Elevated plus-maze Open Field | Anxiolytic-like | No change | DR+ | [24] | ||
Oral | Mouse | Marble-burying Light/Dark | Anxiolytic-like | No change | DR+ | [25] | |||
Inhalation | rats | Social interaction Open Field Elevated plus-maze | Anxiolytic-like | No change | DR+ | [26] | |||
Oral | Mouse | Light/Dark | Anxiolytic-like | No change | 5-HT1A-receptors | DR+ | [27] | ||
i.p. (acute) | Mouse | Elevated plus-maze | Anxiolytic-like | Not evaluated | DR+ | [28] | |||
i.p. (acute) | Mouse | Elevated plus-maze | Anxiolytic-like | Not evaluated | GABA partial agonist? | Reduced diazepam anxiolytic-effect DR+ | [29] | ||
Citrus aurantium subsp. bergamia | Rat | Elevated plus-maze | Anxiolytic-like? | Increase? | inverted U-shaped curve DR+ decrease increase corticosterone induced by behavioral test | [30] | |||
Citrus junos | Inhalation | Mouse | Elevated plus-maze Light/Dark | Anxiolytic-like Anxiolytic-like | No change | DR+ | [31] | ||
Coriandrum sativum var. microcarpum | Inhalation (repeated) | Rats | Elevated plus-maze | Decrease anxiogenic-like effect of icv beta-amyloid (1–42) | Not evaluated | Not tested in naive rats DR− | [32] | ||
Lemon | Inhalation (continuous for 1 week) | Rat (male/female) | Elevated plus-maze | Anxiogenic-like | No change | DR− | [33] | ||
Inhalation | Mouse | Elevated plus-maze | Anxiolytic-like? | Decrease | 5-HTergic (5-HT1A) GABA-A/BZP and DAminergic | DR− | [34] | ||
Citrus limon | Oral (acute) | Mouse | Elevated plus-maze | Anxiolytic-like? | Decrease | inverted U-shaped curve DR+ | [35] | ||
Citrus latifolia | Oral | Mouse | Marble-burying Light/Dark | Anxiolytic-like Anxiolytic-like | No change | inverted U-shaped curve DR+ | [36] | ||
Citrus reticulata | Oral | Mouse | Marble-burying Light/Dark | Anxiolytic-like No effect | No change | DR+ | [36] | ||
Citrus sinensis | Inhalation | Rat | Light/Dark Elevated plus-maze | Anxiolytic-like Anxiolytic-like | No change | Melaleuca alternifolia essential oil used as neutral odor control DR+ | [37] | ||
Copaifera reticulata | Oral (acute) | Rat | Elevated plus-maze | Anxiolytic-like | No change | DR+ | [38] | ||
Cymbopogon citratus | Oral | Mouse | Open Field Elevated plus-maze Light/Dark | Anxiolytic-like | No change | DR+ | [39] | ||
Oral | Mouse | Marble-burying Light/Dark | Anxiolytic-like | No change | GABA-A /BDZ | DR+ | [40] | ||
Dennettia tripetala | i.p. (acute) | Mice (male/Female) | Elevated plus-maze | Anxiolytic-like * (see observation) | Not evaluated | Inconsistency in data showed in figure and text Gender not considered DR+ | [41] | ||
Ducrosia anethfolia | Oral (acute) | Mouse | Elevated plus-maze | Anxiolytic-like | No change | DR+ | [42] | ||
Foeniculum vulgare | Oral | Mouse | Elevated plus-maze Staircase test Open-field | Anxiolytic-like Anxiolytic-like Anxiolytic-like | No change | inverted U-shaped curve DR+ | [43] | ||
Lavandula officinalis | i.p. | Mouse | Geller conflict Vogel conflict | Anxiolytic-like Anxiolytic-like | No change | DR+ | [44] | ||
Lavandula angustifolia | Inhalation | Mouse | Elevated plus-maze | No effect | DR− | [34] | |||
Inhalation (24 h) Inhalation (7 days) | Gerbil (male/female) | Elevated plus-maze | Anxiolytic-like Anxiolytic-like | Anxiolytic in male and female Inclusion of ethological measures One-tailed test DR+ | [45] | ||||
Lavandula angustifolia | Inhalation | rat | Open Field | Anxiolytic-like | Not evaluated (total locomotion) | Increase immobility (sedation) Inclusion one group also exposed during the open-field DR+ | [46] | ||
Inhalation | rat | Open Field | Anxiolytic-like | No change | Reduction in c-fos increases with open field exposition DR− | [47] | |||
Inhalation | Sheep | Reaction to stress (isolation) | Mixed results | change | Nervous sheep: anxiogenic; calm sheep: anxiolytic-like effect DR− | [48] | |||
Inhalation | Mouse | Elevated plus-maze | Anxiolytic-like | No change | Anxiolytic-like effect correlated with linalool/linalyl acetate content DR− | [49] | |||
Inhalation | Mouse | Elevated plus-maze | Anxiolytic-like | Similar effect in stressed and non-stressed mice DR− | [50] | ||||
Inhalation | Mouse | Elevated plus-maze Marble-burying | Anxiolytic-like Anxiolytic-like | No change | Serotonergic system (5-HT1A) Not mediated by GABA-A/BDZ | Neutral odor control DR+ | [51] | ||
Inhalation | Mouse | Marble-burying | Anxiolytic-like | No change | Similar effects in anosmic and normal mice DR+ | [52] | |||
Lavandula angustifolia | Inhalation | Mouse | Elevated plus-maze | Anxiolytic-like | Increase hippocampal 5-HT turn-over | Similar effects in anosmic and normal mice DR− | [53] | ||
Lavandula angustifolia (silexan) | i.p. (repeated) | rat | Elevated plus-maze Open Field Elevated zero-maze Social interaction test Novelty-induced suppressed feeding latency test | Anxiolytic-like Anxiolytic-like Anxiolytic-like Anxiolytic-like Anxiolytic-like | Mixed results | Some results could be influenced by motor activity changes DR+ | [54] | ||
Oral (repeated) | Mouse | Elevated plus-maze | Anxiolytic-like | No change | Non selective inhibition of voltage operated calcium channels | DR+ | [55] | ||
Lippia alba | i.p. | Mouse | Elevated-plus-maze | Anxiolytic-like | No change | DR+ | [56] | ||
i.p. (acute) | Rat | Elevated T-maze | Anxiolytic-like | No change | DR+ | [57] | |||
Litsea cubeba | Oral (7 days) | Mouse | Elevated plus-maze | Anxiolytic-like? | Decrease | DR+ | [58] | ||
Ocimum gratissimum L. | Inhalation (acute) | Mouse | Light/Dark | Anxiolytic-like? | Decrease | inverted U-shaped curve DR+ | [59] | ||
Ocimun sanctum L. | Inhalation (repeated) | Rat | elevated plus-maze | Decrease anxiogenic-like effect of icv beta-amyloid (1–42) | No change | Not tested in naive rats DR+ | [60] | ||
Ocimum basilicum L. | Inhalation (repeated) | Rat | elevated plus-maze | Decrease anxiogenic-like effect of icv beta-amyloid (1–42) | No change | Not tested in naive rats DR+ | [60] | ||
Piper guineense | Inhalation (acute) | Mouse | Light/Dark | Anxiolytic-like? | Mixed results | DR+ | [61] | ||
Propolis | Oral (14 days) | Mouse | Elevated plus-maze | Anxiolytic-like | No change | Effect in stressed mice DR+ | [62] | ||
Rat | Elevated plus-maze Open-field | Anxiolytic-like? | Increase | Female (estrous phase not specified) DR+ | [63] | ||||
Rose centifolia | i.p. | Mouse | Geller conflict Vogel | Anxiolytic-like Anxiolytic-like | No change | DR+ | [64] | ||
Rose | Inhaled | Rat | Elevated plus-maze | Anxiolytic-like | Not evaluated | DR+ | [65] | ||
Inhalation (acute) | Mouse | Elevated plus-maze | No effect | No change | Ethanol as control DR− | [34] | |||
Rose damascena | Prolonged Inhalation (24 h) Repeated Inhalation (14 days) | Gerbil | Elevated plus-maze Light/Dark | No effect Anxiolytic-like? | Mixed | DR− | [66] | ||
Santalum album L. | Inhalation (acute) | Mouse | Elevated plus-maze | Anxiolytic-like in stressed mice | Not evaluated | No effect in non-stressed mice DR− | [67] | ||
Spiranthera odoratissima A. St. Hil. | Oral (acute) | Mouse | Elevated plus-maze Light/Dark Open-field | Anxiolytic-like Anxiolytic-like Anxiolytic-like | No change | 5-HTergic (5-HT1A) Not mediated by GABA-A/BDZ | DR+ | [68] | |
Stachys tibetica | Oral (3 days) Oral (7 days) | Rat | Elevated plus-maze Social Interaction Light/Dark Holeboard Elevated plus-maze | Anxiolytic-like Anxiolytic-like Anxiolytic-like Anxiolytic-like Anxiolytic-like | No change | DR+ | [69] | ||
Thujopsis dolabrata | Elevated plus-maze | Anxiolytic-like | Decrease | 10 min session DR+ | [70] |
Compound | Experimental Protocol | Anxiolytic-Like Effect and/or Mechanism | Animal Tested | Reference |
---|---|---|---|---|
1,4-Cineole | Elevated plus-maze test Holeboard test | Increased exploration of the open arms Increased head dipping | Mice | [71] |
α-Asarone | Elevated plus-maze test Holeboard test Open field test | Decreases in open-arm exploration Increased time spent for head dips Increase in the total number of line crossings | Rats | [72] |
α-Pinene | Elevated plus-maze test | Increased open arm exploration in the elevated plus maze | Mice | [73] |
β-Caryophyllene | Elevated plus-maze test Light/dark test Marble-burying test Open-field test | Increased open arm exploration Increased time spent in light side, and number of transitions Decreased number of marbles buried Increased time spent in the center | Mice | [68,74] |
Citral | Elevated plus-maze test | No effect was observed | Mice | [75] |
Myrcene | ||||
Carvacrol | Elevated plus-maze test | Increased % time spent and % entries in the open arms | Mice | [76] |
Carvacryl acetate | Elevated plus-maze test Light-dark box test Marble-burying test | Increased mouse motor activity Anxiolytic-like effect | Mice | [77] |
(R)-(-)-Carvone | Elevated-T maze test | Reduced avoidance latency without any effect in escape time | Rats | [57] |
Citronellol | Geller conflict test | Increased punished behavior at dose that did not change unpunished behavior | Mice | [64] |
2-Phenethyl alcohol | Vogel conflict tests | Increased punished licking | ||
(E)-Methyl isoeugenol | Elevated plus-maze test Light/dark test Open field test | Increased time spent and % entries in the open arms Increased number of transitions and time spent in light side Increased crossing of the center | Mice | [78] |
Nerol | Elevated plus-maze test Open field test Light/dark test Rota rod test | Increased number of entries and time of permanence in the open arms Decrease in motor activity Increased time of permanence in the room clear No modification in time spent or number of falls in the revolving bar | Mice | [79] |
Isopropyl N-methylanthranilate | Light/dark test Open field test | Increased time spent in the light side without effect on the number of crossing | Mice | [80] |
Methyl N-methylanthranilate | ||||
Isopulegol | Elevated plus-maze test Holeboard test Open field test | Increased number of entries and time spent in the open arms Increase number of head dips Did not change the number of crossing | Mice | [81] |
(R)-(+)-Limonene | Elevated plus-maze test Light/dark test | Increase in time spent and in the number of entries in the open arms Increased time spent in the light side of the light/dark apparatus | Mice | [31,82] |
(+)-Limonene epoxide | Marble burying test | Reduction in number of buried marbles | Mice | [83] |
Linalool | Light/dark test Elevated plus-maze test | Increased time spent in the light side and increased social interaction Increased number of visits to the open arms | Mice | [84] |
Linalool oxide | Light/dark test | Increased number of crossings and time spent in the light side | Mice | [85] |
Myrtenol | Elevated plus-maze test Light/dark test | Increase in open arm exploration Elevated time spent in the light side of light/dark apparatus | Rats | [86] |
Phytol | Elevated plus-maze test | Increased social interaction and decreased number of marbles buried | Mice | [87] |
Pulegone | Elevated plus-maze test Open field test Rota rod test Grasping test Conditioning place preference (CPP) test | Increased mouse motor activity Increased ambulatory activity of mice in a dose-dependent and bell-shaped manner Decreased performance on the Rota rod apparatus Decreased grasping strength Decreased percentage of time spent in the least preferred compartment | Mice | [88] |
Thymol | Brief mechanical restraint Open-field test | Reduced struggle latency and increased struggle bouts, which would be indicative of fear reduction No effect on motor activity | Quail | [89] |
Vanillin | Elevated plus-maze test Bright and dark arena | Increase in the percentile ratio of open arm to total arm entries and reduction in the time spent in the closed arms Increased number of bright chamber entries, time spent, and rears in bright arena | Rats | [90] |
2.5. Alpinia zerumbet
2.6. Angelica sinensis
2.7. Chamaecyparis obtusa
2.8. Casimiroa pringlei
2.9. Celastarus paniculatus
2.10. Citrus Genus
2.10.1. Citrus sp.
2.10.2. Citrus aurantium (Sour/Bitter Orange)
2.10.3. Citrus aurantium subsp. bergamia (Bergamot)
2.10.4. Citrus latifolia and C. reticulata
2.10.5. Citrus junos
2.10.6. Citrus limon
2.10.7. Citrus sinensis (Sweet Orange)
2.11. Copaifera reticulata Ducke
2.12. Coriandrum sativum Var. microcarpum
2.13. Cymbopogon citratus
2.14. Dennettia tripetala
2.15. Ducrosia anethifolia
2.16. Foeniculum vulgare
2.17. Lavendula angustifolia
2.18. Lippia alba
2.19. Litsea cubeba
2.20. Ocimum basilicum L. and Ocimun sanctum L. Essential Oil
2.21. Ocimum gratissimum L.
2.22. Piper guineense
2.23. Propolis
2.24. Rose
2.25. Santalum album L.
2.26. Spiranthera odoratissima A. St. Hil.
2.27. Stachys tibetica
2.28. Thujopsis dolabrata
2.29. Constituents from Essential Oils with Anxiolytic-Like Activity
2.29.1. 1,4-Cineole
2.29.2. α-Asarone
2.29.3. α-Pinene
2.29.4. β-Caryophyllene
2.29.5. Citral and Myrcene
2.29.6. Carvacrol
2.29.7. Carvacryl Acetate
2.29.8. (R)-(−)-Carvone
2.29.9. Citronellol and 2-Phenethyl Alcohol
2.29.10. (E)-Methyl Isoeugenol
2.29.11. Nerol
2.29.12. Isopropyl N-Methylanthranilate and Methyl N-Methylanthranilate
2.29.13. Isopulegol
2.29.14. (R)-(+)-Limonene and (+)-Limonene Epoxide
2.29.15. Linalool and Linalool Oxide
2.29.16. Myrtenol
2.29.17. Phytol
2.29.18. Pulegone
2.29.19. Thymol
2.29.20. Vanillin
2.30. General Discussion
3. Methodology
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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De Sousa, D.P.; Hocayen, P.D.A.S.; Andrade, L.N.; Andreatini, R. A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models. Molecules 2015, 20, 18620-18660. https://doi.org/10.3390/molecules201018620
De Sousa DP, Hocayen PDAS, Andrade LN, Andreatini R. A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models. Molecules. 2015; 20(10):18620-18660. https://doi.org/10.3390/molecules201018620
Chicago/Turabian StyleDe Sousa, Damião Pergentino, Palloma De Almeida Soares Hocayen, Luciana Nalone Andrade, and Roberto Andreatini. 2015. "A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models" Molecules 20, no. 10: 18620-18660. https://doi.org/10.3390/molecules201018620
APA StyleDe Sousa, D. P., Hocayen, P. D. A. S., Andrade, L. N., & Andreatini, R. (2015). A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models. Molecules, 20(10), 18620-18660. https://doi.org/10.3390/molecules201018620