(+)-Dehydrofukinone modulates membrane potential and delays seizure onset by GABAa receptor-mediated mechanism in mice

Garlet, Quelen Iane; Pires, Luana da Costa; Milanesi, Laura Hautrive; Marafiga, Joseane Righes; Baldisserotto, Bernardo; Mello, Carlos Fernando; Heinzmann, Berta Maria

doi:10.1016/j.taap.2017.07.010

Cited by 18 publications

(10 citation statements)

References 92 publications

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“…As shown in Figure 1 and Table 1 , a total of 68 compounds were identified, accounting for 98.244% of the AEO, in which many active compounds with neural regulative function were found, including benzylacetone (compound 1 in Table 1 ), which has been reported to have a sedative effect on mice [ 12 ], butylated hydroxytoluene [ 26 ] (compound 12 ) and farnesene [ 27 ] (compound 24 ) which are known to have a neuroprotective effect. Additionally, dehydrofukinone (compound 59 ) has been proven to be a sedative or anesthetic agent through the GABA A receptor in fish, and has suppressed neuronal excitability through GABAergic neuronal inhibition in mice [ 28 , 29 ]. Verbenol (compound 10 ) has shown action on δ subunit-containing GABA A receptors [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Agarwood Essential Oil Displays Sedative-Hypnotic Effects through the GABAergic System

Wang

Peng

et al. 2017

Molecules

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Although agarwood has been used as a tranquilizer in Asian countries for hundreds of years, the underlying pharmacological basis is still unclear. This study investigated the sedative-hypnotic effect of agarwood essential oil (AEO) using locomotor activity and pentobarbital-induced sleeping assays in mice. Single (1-day) and multiple (7- and 14-days) administrations of 60 mg/kg AEO generated significant sedative effect on inhibiting locomotor activity and hypnotic effect on pentobarbital-induced sleeping in mice. Interestingly, prolonged AEO treatment did not result in obvious desensitization. Concoitant measurement of the levels of brain neurotransmitters using ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) indicated that AEO had no significant effect on the levels of glutamic acid (Glu) and γ-aminobutyric acid (GABA) in the brain. However, the sedative-hypnotic effects were blocked by the type A GABA (GABAA) receptor antagonists bicuculline and flumazenil. In addition, AEO significantly elevated the expression of GABAA receptor subunits and subtypes in the cerebral cortex. Furthermore, AEO increased chlorine ion (Cl−) influx through GABAA receptors in human neuroblastoma cells. These results together demonstrate that AEO exerts its sedative-hypnotic effects through regulating gene expression of GABAA receptors and potentiating GABAA receptor function.

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Section: Discussionmentioning

confidence: 99%

Agarwood Essential Oil Displays Sedative-Hypnotic Effects through the GABAergic System

Wang

Peng

et al. 2017

Molecules

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“…(+)-Dehydrofukinone ( Figure 4 ), also known as dihydrokaranone, is an eremophilane-type sesquiterpenoid ketone isolated from Nectandra grandiflora Ness (Lauraceae) EO. Recent behavioral studies have indicated that dehydrofukinone has sedative and anesthetic properties mediated by GABAergic mechanisms in fish [ 70 ], and induces sedation and anesthesia by modulation of GABA A receptors in a mouse model [ 73 ], suggesting that the natural compound (+)-dehydrofukinone has therapeutic potential as a suppressor of neuronal excitability.…”

Section: The Pharmacological Properties Of Constituents Isolated Fmentioning

confidence: 99%

Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases

Wang

Heinbockel

2018

Molecules

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Essential oils and the constituents in them exhibit different pharmacological activities, such as antinociceptive, anxiolytic-like, and anticonvulsant effects. They are widely applied as a complementary therapy for people with anxiety, insomnia, convulsion, pain, and cognitive deficit symptoms through inhalation, oral administration, and aromatherapy. Recent studies show that essential oils are emerging as a promising source for modulation of the GABAergic system and sodium ion channels. This review summarizes the recent findings regarding the pharmacological properties of essential oils and compounds from the oils and the mechanisms underlying their effects. Specifically, the review focuses on the essential oils and their constituents targeting the GABAergic system and sodium channels, and their antinociceptive, anxiolytic, and anticonvulsant properties. Some constituents target transient receptor potential (TRP) channels to exert analgesic effects. Some components could interact with multiple therapeutic target proteins, for example, inhibit the function of sodium channels and, at the same time, activate GABAA receptors. The review concentrates on perspective compounds that could be better candidates for new drug development in the control of pain and anxiety syndromes.

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“…Whole-cell electrophysiology experiments showed that dehydrofukinone induced hyperpolarization, decreasing calcium mobilization from the synapse. Activity could be blocked by flumazenil, indicating that the compound's mechanism is GABAergic neuronal inhibition [41]. Smyrnium cordifolium EO, which is high in the sesquiterpenes curzerene, cadinene, and elemene, protected PTZ mice against all convulsions and mortality at a dose of 0.4 mg/kg [35].…”

Section: Resultsmentioning

confidence: 99%

The Effects of Various Essential Oils on Epilepsy and Acute Seizure: A Systematic Review

Bahr

Rodriguez²,

Beaumont³

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Many essential oils (EOs) have anticonvulsant activity and might benefit people with epilepsy. Lemongrass, lavender, clove, dill, and other EOs containing constituents such as asarone, carvone, citral, eugenol, or linalool are good candidates for evaluation as antiepileptic drugs. On the other hand, some EOs have convulsant effects and may trigger seizures in both epileptic and healthy individuals. Internal use of EOs like sage, hyssop, rosemary, camphor, pennyroyal, eucalyptus, cedar, thuja, and fennel can cause epileptic seizures because they contain thujone, 1,8-cineole, camphor, or pinocamphone, which have been identified as convulsive agents. While more research is needed to confirm their mechanisms of action, it appears that the convulsant or anticonvulsant properties of essential oils are largely due to (1) their ability to modulate the GABAergic system of neurotransmission and (2) their capacity to alter ionic currents through ion channels. This review presents a systematic analysis of the current research on EOs and epilepsy, including human case studies, animal models, andin vitrostudies.

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(+)-Dehydrofukinone modulates membrane potential and delays seizure onset by GABAa receptor-mediated mechanism in mice

Cited by 18 publications

References 92 publications

Agarwood Essential Oil Displays Sedative-Hypnotic Effects through the GABAergic System

Agarwood Essential Oil Displays Sedative-Hypnotic Effects through the GABAergic System

Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases

The Effects of Various Essential Oils on Epilepsy and Acute Seizure: A Systematic Review

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