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
2.3. EOs with Anticonvulsant and Other Pharmacological Properties
3. The Pharmacological Properties of Constituents Isolated from EOs and the Underlying Mechanisms of Action
3.1. Analgesic and Anticonvulsant Properties
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 sleeping 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