Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases
Abstract
:1. Introduction
2. The Pharmacological Activities of EOs and the Underlying Mechanism of Their Actions
2.1. EOs with Antinociceptive and Anti-Inflammatory Activities
2.2. EOs with Anxiolytic, Anti-Depressive, and Sedative Activities
3.1.1. Terpenoids with Analgesic Properties Targeting Na+ and TRP Channels
3.1.2. Terpenes with Analgesic and Anticonvulsant Properties Targeting GABAA Receptors
3.1.3. Phenylpropanoid Derivative Constituents with Analgesic Properties and the Mechanisms of Action
3.2. Anxiolytic, Sedative, and Anti-Depressive Properties
3.2.1. Terpenes with Anxiolytic and Sedative Properties Targeting the GABAergic System
3.2.2. Terpenes with Other Pharmacological Properties
3.2.3. Non-Terpene Constituents with Anticonvulsant, Anxiolytic Properties, and Their Underlying Mechanisms
3.3. Terpenes with Convulsive Activities Acting as GABAA Receptor Antagonists
4. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
References
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EO Botanical Origins | Administration | Pharmacological Effects | Mechanism of Actions | Authors/Year/Ref. |
---|---|---|---|---|
Achillea Wilhelmsii C. Koch | i.p. | anxiolytic effects | not probably mediated through GABA and opioid receptors | Majnooni et al., 2013 [19] |
Acorus gramineus Rhizoma | INH; p.o. | pentylenetetrazole-induced convulsion; sedative effect; CNS inhibitory effects | increased GABA level; decreased GABA transaminase | Koo et al., 2003 [20] |
Acorus tatarinowii Schott | analgesic effects | inhibited Na+ channels | Moreira-Lobo et al., 2010 [17] | |
Aloysia citrodora Palau | in vitro | effective antioxidant, radical-scavenging activities, and neuronal protection | inhibited [3H] nicotine binding | Abuhamdah et al., 2015 [21] |
Artemisia herba-alba | in vitro | antifungal and anti-inflammatory activities | N/A | Abu-Darwish et al., 2015 [22] |
Artemisia ludoviciana | i.p. | antinociceptive activity | partially mediated by the opioid system | Anaya-Eugenio et al., 2016 [23] |
Artemisia judaica | in vitro | antifungal and anti-inflammatory activities | N/A | Abu-Darwish et al., 2016 [24] |
Artemisia dracunculus | i.p. | peripheral and central antinociceptive activity | N/A | Maham et al., 2014 [25] |
Asarum heterotropoides | INH | decreased depression-like behaviors | N/A | Park et al., 2015 [26] |
Camellia sinensis | INH | increased slee** time | potentiated GABAA receptors | Hossain et al., 2004 [27] |
Citrus aurantium | p.o. | anxiolyticlike activity | serotonergic system (5-HT1A receptors) | Costa et al., 2013 [28] |
Citrus bergamia | decreased stress-induced anxiety | tuning synaptic plasticity | Bagetta et al., 2010 [29] | |
Citrus sinensis | INH | acute anxiolytic activity | N/A | Faturi et al., 2010 [30] |
Coriander | INH | increased anxiolytic–antidepressant-like behaviors, and | N/A | Cioanca et al., 2014 [31] |
Cymbopogon citratus | p.o. | anxiolytic-like activity | potentiated GABAA receptor complex | Costa et al., 2011 [13] |
Cymbopogon winterianus Jowitt; and C. citratus (DC) Stapf. | i.p. | anticonvulsant activities | via GABAergic neurotransmission | Silva et al., 2010 [32] |
Dysphania graveolens | p.o. | antinociceptive effects | N/A | Déciga-Campos et al., 2017 [33] |
Hyptis mutabilis (Rich.) Briq. | p.o. | sedative and central anesthetic activities | no involvement of the GABAA-BDZ system | Silva et al., 2013 [34] |
Lavandula angustifolia | INH | anxiolytic-like effects | serotonergic system | Chioca et al., 2013 [35] |
Lippia alba (Mill.) N.E. Brown | p.o. | central anesthetic effect | involvement of the GABAergic system | Heldwein et al., 2012 [36] |
Lemon oil | anxiolytic, antidepressant-like effects | suppression of DA activity related to enhanced 5-HTnergic neurons | Komiya et al., 2006 [37] | |
Melissa officinalis | p.o. | anti-agitation effects in patients and the depressant effects in in-vitro | inhibited GABA-induced currents | Abuhamdah et al., 2008 [38] |
Nigella sativa Seed lmain components | p.o. | potentiation of valproate-induced anticonvulsant effect | increased in GABAergic response | Raza et al., 2008 [39] |
Perfume and phytoncid | in vitro | anxiolytic anticonvulsant and sedative activity | potentiating GABAA receptors | Aoshima and Hamamoto, 1999 [40] |
Piper guineense | INH | sedative and anxiolytic-like effects | N/A | Tankam and Tto, 2013 [2] |
Pistacia integerrima Stewart ex Brandis Galls | in vitro | relaxant and spasmolytic effects | involvement of β-adrenoceptors and calcium channels | Shirole et al., 2015 [41] |
Salvia sclarea | i.p. or INH | anti-depressant-like effect | modulating DAnergic pathway | Seol et al., 2010 [42] |
Syzygium aromaticum | local anesthesia | Inhibited sodium channels | Huang et al., 2012 [43] | |
Tagetes minuta L | sc | anxiogenic-like effects | negative modulation on the GABAergic function | Marin et al., 1998 [44] |
Thymus capitatus Hoff. et Link. | p.o. | antinociceptive activity | via peripheral nervous excitability blockade | Gonçalves et al., 2017 [45] |
Valerian officinalis L | p.o. | sedatives | N/A | Houghton, 1999 [46] |
Constituents | Pharmacological Effects | Mechanism of Actions | Authors/Year/Ref. |
---|---|---|---|
1,8-Cineole | antinociceptive, smooth muscle relaxant | reduction of excitability of peripheral neurons by blocking voltage-dependent Na+ current | Ferreira-da-Silva et al., 2015 [64] |
neuronal excitant | hyperexcitability and epileptiform activity in snail neurons by inhibiting potassium channels | Zeraatpisheh and Vatanparast, 2015 [65] | |
1-Nitro-2-phenylethane | hypnotic, anti-convulsant and anxiolytic effects | N/A | Oyemitan et al., 2013 [66] |
vasorelaxant effects in rat isolated aortic rings | inhibition of contractile events that are clearly independent of Ca2+ influx | Arruda-Barbosa et al., 2014 [67] | |
vasorelaxant effects | N/A | Interaminense et al., 2013 [68] | |
(+)-Borneol | alleviated mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain | enhanced GABAAR-mediated GABAergic transmission | JIang et al., 2015 [69] |
(+)- and (−)-Borneol | analgesia and anesthesia | positive modulation of GABAAR | Granger et al., 2005 [14] |
(+)-Dehydrofukinone | sedative or anesthetic effects | interacted with GABAergic receptors; a suppressor of neuronal excitability | Garlet et al., 2016 [70] |
(S)-Limonene, | Anti-stress effect | via the GABAergic system | Zhou et al., 2009 [71] |
(R)-(+)-Limonene | anxiolytic-like effects | N/A | Lima et al., 2013 [72] |
(+)-Dehydrofukinone | sedation, anticonvulsant and anesthesia | potentiated GABAA receptors | Garlet et al., 2017 [73] |
α-asarone | antiepileptic effect | enhanced tonic GABAergic inhibition | Huang et al., 2013 [54] |
antiepileptic effect | Na+ channel blockade and activation of GABAA receptors | Wang ZJ et al., 2014 [4] | |
anticonvulsant | blocked Na+ channel, potentiated GABAA receptors | Wang ZJ et al., 2014 [4] | |
α-(−)-Bisabolol | antinociceptive-like effect | decreased peripheral nerve excitability probably by blockade of voltage-gated Na+ channels | Wang YW et al., 2015 [74] |
α-Pinene | anxiolytic and hypnotic effects | a partial modulator of GABAA receptors and directly binding to the benzodiazepine binding site of GABAA receptor. | Yang et al., 2016 [75] |
β-Citronellol | Hypotensive action | antagonized transmembrane Ca2+ influx from the extracellular milieu to produce myorelaxant actions. | Vasconcelos et al., 2016 [76] |
(R)-(−)-carvone and (S)-(+)-carvone | antimanic-like effects | blockade of voltage-gated Na+ channels; activating TRPV1 and TRPA1 channels | Nogoceke et al., 2016 [77] |
Benzyl benzoate | anxiolytic effect | probably through 5-HTnergic and DAnergic pathways | Alves et al., 2016 [63] |
Carvacrol | antinematodal action | nicotinic acetylcholine receptors and GABA receptors | Trailović et al., 2015 [78] |
analgesic activity | reduced excitability of peripheral neurons; reduced voltage-dependent Na+ current | Joca et al., 2012, 2015 [79,80] | |
anxiolytic effects in the plus-maze test | involvement with GABAergic transmission | Melo et al., 2010 [81] | |
Estragole | anxiolytic and antimicrobial activities | inhibition of neuronal excitability by blocking Na+ channels | Silva-Alves et al., 2013 [82] |
Eugenol | local analgesic | inhibition of Na+ channels | Vatanparast, 2017 [83] |
analgesic | reduced neuronal hyperexcitability by blocking Na+ currents | Huang et al., 2012 [43] | |
inhibition of action potentials | Moreira-Lobo et al., 2010 [17] | ||
Isopulegol | pentylenetetrazol-induced convulsions | positive modulation of GABAAR and antioxidant properties | Silva et al., 2009 [84] |
Linalool | antinociceptive effect | blocked excitability by decreasing the voltage-dependent Na+ current in dorsal root ganglion neurons | Leal-Cardoso et al., 2010 [85] |
Menthol | analgesia | blocked action potentials in frog sciatic nerves unassociated with TRPM8 activation | Kawasaki et al., 2013 [86] |
Methyleugenol | anticonvulsant, antinociceptive and anesthetic activities | agonist of GABAA receptors in cultured hippocampal neurons | Ding et al., 2014 [87] |
antinociceptive effect | inhibition of NMDA receptor-mediated hyperalgesia via GABAA receptors | Yano et al., 2006 [88] | |
antinociceptive and anesthetic actions | inhibition of Nav1.7 channels | Wang ZJ et al., 2015 [5] | |
Myrtenol and Verbenol | sedative, anxiolytic and anticonvulsive effects | augments phasic and tonic GABAergic inhibition; positive allosteric modulation of GABAA receptors | van Brederode et al., 2016 [16] |
Nerolidol | antinociceptive and anti-inflammatory activity | involvement of the GABAergic system and proinflammatory cytokines | Fonsêca et al., 2016 [89] |
Terpinen-4-ol | anticonvulsant effects | involvement of the GABAergic system, and decrease Na+ current | Nóbrega et al., 2014 [90] |
Thujone | muscle spasms and convulsions | GABA receptor antagonist | Mariani et al., 2016 [91] |
Thymol | antinociception | nerve conduction inhibition; activated TRPA1 channels; a positive allosteric modulator of human GABAAR | Xu et al., 2015 [92] Priestley et al., 2003 [93] |
Thymoquinone | anticonvulsant effects | opioid receptor-mediated increase in GABAergic tone | Hosseinzadeh and Parvardeh, 2004 [94] |
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Wang, Z.-J.; Heinbockel, T. Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases. Molecules 2018, 23, 1061. https://doi.org/10.3390/molecules23051061
Wang Z-J, Heinbockel T. Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases. Molecules. 2018; 23(5):1061. https://doi.org/10.3390/molecules23051061
Chicago/Turabian StyleWang, Ze-Jun, and Thomas Heinbockel. 2018. "Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases" Molecules 23, no. 5: 1061. https://doi.org/10.3390/molecules23051061