Essential Oils and Their Constituents: An Alternative Source for Novel Antidepressants
Abstract
:1. Introduction
2. Pharmacological Management of Major Depression
3. Methodology
4. Clinical Effects of Essential Oils on Mood Depression
5. Antidepressant-Like Effects of Essential Oils: Evidence from Animal Studies
5.1. Asarum heterotropoides F. Schmidt (Aristolochiaceae)
5.2. Citrus limon L. Osbeck
5.3. Eugenia uniflora L.
5.4. Perilla frutescens L. Britton
5.5. Salvia sclarea L.
5.6. Syzygium aromaticum (L.) Merr. & L.M. Perry
5.7. Toona ciliata var. yunnanensis (C. DC.) C.Y. Wu
5.8. Valeriana wallichii DC.
6. Constituents from Essential Oils with Antidepressant-Like Activity
6.1. Isolated Constituents with Proposed Mechanisms of Antidepressant Action
6.2. Isolated Constituents without Antidepressant Mechanism of Action
7. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Essential Oils | Administration via and Duration of Treatment | Animal Specie | Dose Range Tested and Minimal Active Dose | Behavioral Test | Observed Effects | Mechanism of Action | Observations | Reference |
---|---|---|---|---|---|---|---|---|
Acorus tatarinowii Schott | Oral gavage, acute | ICR mouse | 30–240 mg/kg (60 mg/kg) | FST, TST | Reduced immobility time in both assays | DR+ | [33] | |
U-inverted curve | ||||||||
Controls: negative and positive (imipramine) | ||||||||
Asarum heterotropoides F. Schmidt | Inhalation, acute | ICR mouse | 0.25–2.0 g (0.25 g) | FST, TST | Reduced immobility time in both tests | Reversed the increase of CRF- and TH-positive cells in the paraventricular nucleus, and locus coeruleus, respectively; | DR+ Controls: negative and positive (fluoxetine) | [34] |
Reversed the decrease of 5-HT-positive cells in the dorsal raphe nucleus | ||||||||
Citrus limon (L.) Osbeck | Inhalation, acute | ICR mouse | Saturated chamber (90 min) | FST | Reduced immobility time | The treatment with flumazenil (GABAA antagonist), buspirone (5-HT1A partial agonist), DOI (5-HT2A receptor agonist), miaserin (5-HT2A/C receptor agonist), apomorphin (D receptor agonist) and haloperidol (D receptor antagonist) blocked the antidepressant effect. Increased hippocampal DA and prefrontal cortex and hippocampal 5-HT | DR− | [35] |
Controls: negative and positive (fluoxetine and imipramine) | ||||||||
Reduced spontaneous locomotor activity | ||||||||
Citrus limon (L.) Osbeck | Inhalation, acute | SD rats | Saturated chamber (60 min) | FST | Reduced immobility time | DR− | [36] | |
Controls: negative and positive (imipramine) | ||||||||
Reduced spontaneous locomotor activity | ||||||||
Citrus limon (L.) Osbeck | Oral gavage, 30 days | Swiss mouse | 50–150 mg/kg (50 mg/kg) | FST | Reduced immobility time | DR+ | [37] | |
Controls: negative and positive (imipramine and paroxetine) | ||||||||
The treatment decreased spontaneous locomotion increased sleeping duration | ||||||||
Eugenia uniflora L. | Oral gavage, acute | Swiss mouse | 1–50 mg/kg (10 mg/kg) | TST | Reduced immobility time | The blockade of 5-HT2A/C, α1 and α2-receptors prevented the antidepressant effects; | DR+ Controls: negative and positive (fluoxetine) | [38] |
In vitro inhibition of linoleic acid peroxidation; | ||||||||
Reduced SNP-induced lipoperoxidation in cortex, hippocampus and cerebellum | ||||||||
Lavandula angustifólia Mill. | Intraperitoneal, acute | SD rat | 5–20% (5%) | FST | Reduced immobility time | DR+ | [39] | |
Controls: negative and positive (fluoxetine and imipramine) | ||||||||
Lavandula angustifólia Mill. | Inhalation, acute | ICR mouse | Saturated chamber (90 min) | FST | No effects were observed | DR− | [35] | |
Controls: negative and positive (fluoxetine and imipramine) | ||||||||
Litsea glaucescens Kunth | Intraperitoneal, three times within 24 h | ICR mouse | 54.8–300 mg/kg (100 mg/kg) | FST | Reduced immobility time | DR+ | [40] | |
Controls: negative and positive (imipramine) | ||||||||
Mentha × piperita L. | Inhalation, acute | ICR mouse (female) | Saturated chamber (10 min) | FST | Reduced immobility time | DR− | [41] | |
Controls: negative | ||||||||
Perilla frutescens L. Britton | Oral gavage, 3 weeks | ICR mouse | 3–9 mg/kg (3 mg/kg) | CUMS, FST, TST, OFT | Restored sucrose preference in CUMS mice; | Reversed the 5-HT and 5-HIAA reduced concentrations in CUMS mice; Restored the serum IL-6, IL-1β, and TNF-α levels in CUMS mice | DR+ | [42] |
Reverted the reduced spontaneous locomotion in CUMS mice; | U-inverted curve | |||||||
Restored increased immobility time in CUMS mice | Controls: negative and positive (fluoxetine) | |||||||
Perilla frutescens L. Britton | Oral gavage, 3 and 4 weeks | ICR mouse | 3–6 mg/kg (3 mg/kg) | CUMS, FST, sucrose preference | Restored the CUMS-induced decreased sucrose preference and increased immobility time | Restored the CUMS-induced reduction of hippocampal protein and mRNA BDNF | DR+ | [43] |
Controls: negative and positive (fluoxetine) | ||||||||
Rosmarinus officinalis L. | Oral gavage, acute | Swiss mouse | 0.1–100 mg/kg (0.1 mg/kg) | TST | Reduced immobility time | DR+ | [44,45] | |
Controls: negative and positive (fluoxetine) | ||||||||
Rosmarinus officinalis L. | Intraperitoneal, acute | SD rat | 5–20% (5%) | FST | Reduced immobility time | DR+ | [39] | |
U-inverted curve | ||||||||
Controls: negative and positive (fluoxetine and imipramine) | ||||||||
Salvia sclarea L. | Intraperitoneal and inhalation, acute | SD rat | 5–20% (5%); satured chamber (1, 2, 4 and 6 h) | FST | Reduced immobility time when injected and inhaled | The pretreatment with haloperidol (Dopamine receptor antagonist), SCH-23390 (D1 receptor antagonist) and buspirone (5-HT1A partial agonist) blocked the antidepressant effect | DR+ | [39] |
Controls: negative and positive (fluoxetine and imipramine) | ||||||||
Schinus terebinthifolius Raddi | Oral gavage, 15 days | Wistar rats | 100 mg/kg | FST | Restored increased immobility time in rats subjected to a model of neuropathic pain | DR− | [46] | |
Controls: negative and positive (ketamine) | ||||||||
Syzygium aromaticum (L.) Merr, & L.M.Perry | Oral gavage, acute | ICR mouse | 50–200 mg/kg (100 mg/kg) | FST, TST | Reduced immobility time in both tests | DR+ | [47] | |
Controls: negative and positive (imipramine) LD50 = 45564.556 g/kg (po) | ||||||||
Syzygium aromaticum (L.) Merr, & L.M.Perry | Oral gavage, 5 weeks | SD rat | 50–200 mg/kg (50 mg/kg) | CUMS, novelty-suppressed feeding behavior | Restored sucrose preference in CUMS rats; Reverted the increased latency to feed in a unfamiliar environment in CUMS rats | Restored hippocampal BDNF protein, p-ERK and p-CREB expression | DR+ | [47] |
Controls: negative and positive (imipramine) | ||||||||
Thymus vulgaris L. (Lamiaceae) | Inhalation, acute | ICR mouse (female) | Saturated chamber (10 min) | FST | Reduced immobility time | DR− | [41] | |
Controls: negative | ||||||||
Toona ciliata Roem. var. yunnanensis (C. DC.) C.Y. WU | Oral gavage, acute | ICR mouse | 10–80 mg/kg (10 mg/kg) | FST, TST | Reduced immobility time in both tests | DR+ | [48] | |
Controls: negative and positive (imipramine) | ||||||||
Toona ciliata Roem var. yunnanensis (C. DC.) C.Y. WU | Oral gavage, acute | SD rat | 10–80 mg/kg (10 mg/kg) | CUMS | No behavioral effects were evaluated | Increased hippocampal monoamines (5-HT, NE and DA) and BDNF contents in CUMS rats; | DR+ Controls: negative and positive (imipramine) | [48] |
Reduced serum corticosterone in CUMS rats | ||||||||
Valeriana wallichii DC. | Oral gavage, acute and 14 days | Albino Laca mouse (male and female) | 10–40 mg/kg (10 mg/kg) | FST | Reduced immobility time | Increased noradrenaline and 5-HT levels after repeated administration; The acute antidepressant effect was prevented by pretreatment with L-arginine (NO precursor) and sildenafil (phosphodiesterase 5 inhibitor), while it was potentiated with L-NAME (NOS inhibitor) and methylene blue (inhibitor of soluble guanylate cyclase) | DR+ | [49] |
Controls: negative and positive (imipramine) | ||||||||
Zingiber officinale Roscoe | Inhalation, acute | ICR mouse (female) | Saturated chamber (10 min) | FST | Reduced immobility time | DR− | [41] | |
Controls: negative |
Constituents | Via of Administration and Duration of Treatment | Animal Specie | Dose Range Tested and Minimal Active Dose | Behavioral Test | Observed Effects | Mechanism of Action | Observations | Reference |
---|---|---|---|---|---|---|---|---|
Intraperitoneal, acute | ICR mouse | 5–20 mg/kg (10 mg/kg) | FST, TST | Reduced immobility time in both assays | DR+ | [33] | ||
Asarone | Controls: negative and positive (imipramine) | |||||||
Intraperitoneal, acute | C57BL/6 mouse | 50 mg/kg | FST, TST, novelty-suppressed feeding behavior | Reduced immobility time in the TST and the FST; decreased feeding latency in the novelty-suppressed feeding test | The pretreatment with AM630 (CB2 antagonist) prevented the anti-immobility effects | DR− | [52] | |
β-Caryophyllene | Controls: negative | |||||||
Oral gavage, acute | Swiss mouse | 12.5–50 mg/kg (12.5 mg/kg) | FST, TST | Reduced immobility time in both tests | The pretreatment with SCH23390 (D1 antagonist) and sulpiride (D2 antagonist) prevented the anti-immobility effects | DR+ | [68] | |
Carvacrol | Controls: negative and positive (imipramine) | |||||||
Oral gavage, 21 days | SD rat, 18 months old | 22.5–90 mg/kg (45 mg/kg) | CUMS | Reversed decreased sucrose preference and spontaneous locomotion in CUMS rats | Reversed the increased hippocampal COX-2 protein and activity; Reversed the elevated PGE2 concentration in frontal cortex and hippocampus in CUMS rats | DR+ | [69] | |
Cinnamic aldehyde | Controls: negative and positive (fluoxetine) | |||||||
Inhalation, acute | SD rats | Saturated chamber (60 min) | FST | Reduced immobility time | DR− | [36] | ||
Controls: negative and positive (imipramine) | ||||||||
Citral | Hypolocomotion | |||||||
Intraperitoneal, acute | Wistar rat | 0.1–0.3 g/kg | FST | No effects | DR+ | [45,70] | ||
γ-Decanolactone | Controls: negative Hypolocomotion at higher doses | |||||||
Intraperitoneal, three times within 24 h | ICR mouse | 100 mg/kg | FST | No effects | DR− | [40] | ||
Eucalyptol | Controls: negative and positive (imipramine) | |||||||
Intraperitoneal, 14 days | ddY mice | 10–100 mg/kg (30 mg/kg) | FST, TST | Reduced immobility time in the TST and increased number of wheel rotations in the FST | Increased Hippocampal BDNF and metallothionein-III (brain-predominant protein that alleviates various neurotoxic events) mRNA | DR+ | [61] | |
Controls: negative and positive (imipramine) | ||||||||
Eugenol | Oral, mixed with drinking water, 14 days | ICR mouse | 0.17 mmol/kg | FST | Increased number of wheel rotations in the FST | Inhibits human MAOA (IC50 34.4 µM) preferencially than MAOB (IC50 288 µM) activity | DR− | [62] |
Controls: negative | ||||||||
Oral gavage, 4 weeks | ICR mouse | 20–40 mg/kg (20 mg/kg) | CUMS, FST, TST | Restored decreased sucrose preference and increased immobility time in the TST and FST in mice subjected to CUMS | Reversed the IL-1β-related CNS inflammation by markedly inhibiting CUMS-induced PFC NF-κB pathway and modulating NLRP3 inflammasome activation (activated caspase 1) in CUMS mice | DR+ | [60] | |
Geraniol | Controls: negative and positive (fluoxetine) | |||||||
Intraperitoneal, acute | Swiss mouse | 25–50 mg/kg (25 mg/kg) | FST, TST | Increased immobility time | DR+ | [71] | ||
Isopulegol | Controls: negative and positive (imipramine) | |||||||
Oral gavage, 15 days | Wistar rat | 10 mg/kg | FST | Restored increased immobility time in rats subjected to a model of neuropathic pain | DR− | [46] | ||
Controls: negative and positive (ketamine) | ||||||||
Limonene | Intraperitoneal, three times within 24 h | ICR mouse | 100 mg/kg | FST | No effects | DR− | [40] | |
Controls: negative and positive (imipramine) | ||||||||
Linalool | Intraperitoneal, three times within 24 h | ICR mouse | 54.8–173.2 mg/kg (100 mg/kg) | FST | Reduced immobility time | DR+ | [40] | |
U-inverted curve | ||||||||
Controls: negative and positive (imipramine) | ||||||||
The treatment reduced spontaneous locomotion | ||||||||
Intraperitoneal, three times within 24 h | ICR mouse | 100 mg/kg | FST | Reduced immobility time | The pretreatment with WAY100,635 (5-HT1A antagonist) and yohimbine (α2-antagonist) prevented the antidepressant-like effects | DR− | [58] | |
Controls: negative and positive (imipramine) | ||||||||
Intraperitoneal, acute | Swiss mouse | 10–200 mg/kg (100 mg/kg) | TST | Reduced immobility time | DR+ | [59] | ||
Controls: negative and positive (imipramine) | ||||||||
Oral gavage, 3 weeks | ICR mouse | 15–30 mg/kg (15 mg/kg) | CUMS, FST, TST | Reversed the decrease of sucrose consumption, the hypolocomotion and the increased immobile time in the TST and FST in CUMS mice | Restored the CUMS-induced reductions in hippocampal NE and 5-HT levels; Reverted the increased hippocampal pro-inflammatory cytokines levels (IL-1β, IL-6, and TNFα) in CUMS mice; Inhibited the increased hippocampal nod-like receptor protein 3 (NLRP3) inflammasome, and caspase-1 protein expression in CUMS mice | DR+ | [72] | |
Menthone | Controls: negative and positive (fluoxetine) | |||||||
Oral gavage, acute | Wistar rats | 1.0–10.0 µl/mL/kg (1.0 µl/mL/kg) | FST | Reduced immobility time | DR+ | [50] | ||
Methyl-eugenol | Controls: negative | |||||||
Intraperitoneal, three times within 24 h | ICR mouse | 100 mg/kg | FST | No effects | DR− | [40] | ||
α-Pinene | Controls: negative and positive (imipramine) | |||||||
β-Pinene | Intraperitoneal, three times within 24 h | ICR mouse | 54.8–173.2 mg/kg (100 mg/kg) | FST | Reduced immobility time | DR+ | [40] | |
Controls: negative and positive (imipramine) | ||||||||
The treatment reduced the spontaneous locomotion | ||||||||
Intraperitoneal, three times within 24 h | ICR mouse | 100 mg/kg | FST | Reduced immobility time | The pretreatment with WAY100,635 (5-HT1A antagonist), propranolol (β-antagonist), DSP-4 (NE neurotoxin), SCH23390 (D1 antagonist) prevented the anti-immobility effect | DR− | [58] | |
Controls: negative and positive (imipramine) | ||||||||
Oral gavage, 7 days | ICR mouse | 60–120 mg/kg (60 mg/kg) | LPS-induced depressant-like behavior, FST and TST | Reversed increased in immobility time in the FST and TST in LPS-treated mice | Reversed the reduced concentrations of 5-HT and NE, and attenuated LPS-induced increases of serum protein levels and prefrontal cortex mRNA of TNF-α and IL-6 | DR+ | [70] | |
Controls: negative and positive (fluoxetine) | ||||||||
Perillaldehyde | Inhalation, 9 days | ddY mouse | 0.1–10% dropped on the area between eyes and nose (1%) | CUMS, FST | Reduced immobility time in naïve mouse and reversed increased immobility time in CUMS mice | DR+ | [57] | |
Controls: negative and positive (minalcipran) | ||||||||
Oral gavage, once daily, 15 days | Wistar rat | 10 mg/kg | FST | Restored increased immobility time in rats subjected to a model of neuropathic pain | DR− | [46] | ||
α-Phellandrene | Controls: negative and positive (ketamine) | |||||||
Oral gavage, 3 weeks | ICR mouse | 15–30 mg/kg (15 mg/kg) | CUMS, TST, FST | Reversed the decrease of sucrose consumption, the loss of body weight, and the increased immobile time in the TST and FST in CUMS mice | Restored the CUMS-induced reductions in hippocampal NE and 5-HT; Reverted the increased hippocampal mRNA of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) in CUMS mice; Inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor, and subsequently decreased the expression of caspase-1 | DR+ | [73] | |
Thymol | Controls: negative and positive (fluoxetine) | |||||||
Intraperitoneal, acute | Swiss mouse | 20 mg/kg | FST, TST | Reduced immobility time in both tests | A significant elevation of 5-HT whole brain levels was observed; Increased glutathione levels and decreased TBARS levels in the whole brain | DR− | [74] | |
Thymoquinone | Controls: negative and positive (fluoxetine) | |||||||
Oral gavage, acute and 10 days | Swiss mouse (male and female) | 10–100 mg/kg (10 mg/kg) | FST, TST | Reduced immobility time under acute and chronic treatments | DR+ | [75] | ||
Vanillin | Controls: negative and positive (fluoxetine and imipramine) |
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De Sousa, D.P.; Silva, R.H.N.; Silva, E.F.d.; Gavioli, E.C. Essential Oils and Their Constituents: An Alternative Source for Novel Antidepressants. Molecules 2017, 22, 1290. https://doi.org/10.3390/molecules22081290
De Sousa DP, Silva RHN, Silva EFd, Gavioli EC. Essential Oils and Their Constituents: An Alternative Source for Novel Antidepressants. Molecules. 2017; 22(8):1290. https://doi.org/10.3390/molecules22081290
Chicago/Turabian StyleDe Sousa, Damião P., Rayanne H. N. Silva, Epifanio F. da Silva, and Elaine C. Gavioli. 2017. "Essential Oils and Their Constituents: An Alternative Source for Novel Antidepressants" Molecules 22, no. 8: 1290. https://doi.org/10.3390/molecules22081290