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

Abstract

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.

The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application

“…The impacts of exposure to essential oils can be classified into psychological impacts and physiological impacts. The psychological impacts found in non-human animals, mostly using mice or rats, are anxiolytic effects, suppression of depression, anti-agitation, as a relaxant, and anti-stress effects [91], which may all be related to a relaxing effect through suppression of anxiety, stress, agitation, and depression. Some studies suggest that English lavender (Lavendula angustifolia) has the strongest anxiolytic effect [92].…”

“…Some studies suggest that English lavender (Lavendula angustifolia) has the strongest anxiolytic effect [92]. The physiological impacts of essential oils are broader, i.e., improving wound healing, as an analgesic, an anti-nociceptive, an anti-fungal, an anti-inflammatory, an anti-oxidant, a local anesthesia, a sedative, an anesthetic systemic, having anti-convulsant effects, and others [91,92] ( Table 2). Studies using human subjects have found differences in effectiveness, depending on the essential oils as shown above.…”

“…This suggests that these chemical compounds activate the same signaling pathway. In our previous study [91], we summarized the receptors and channels that some of the aromatic chemical compounds activate and showed the chemical compounds with similar impacts. For analgesic properties, 1,8-cineole, menthol (both (-)-and (+)-), carvone (both (-)-and (+)-), pulegone, linalyl acetate, linalool, carvacrol, estragole, besabololl, carvone (both (-)-and (+)-), terpinen-4-ol, which are all monoterpenes, are known to have analgesic properties targeting Na + and TRP channels [91].…”

“…In our previous study [91], we summarized the receptors and channels that some of the aromatic chemical compounds activate and showed the chemical compounds with similar impacts. For analgesic properties, 1,8-cineole, menthol (both (-)-and (+)-), carvone (both (-)-and (+)-), pulegone, linalyl acetate, linalool, carvacrol, estragole, besabololl, carvone (both (-)-and (+)-), terpinen-4-ol, which are all monoterpenes, are known to have analgesic properties targeting Na + and TRP channels [91]. TRPV1 to 4 are temperature-sensitive channels activated by heat stimuli, whereas TRPM8 and TRPA1 are temperature-sensitive channels that are activated by cold stimuli [187].…”

“…Studies have shown that GABA has a neuroprotective effect against degeneration, preventing neurotoxic-induced cell death, decreasing apoptosis, and suppressing cytodestructive autophagy [193]. Some studies have also reported that GABA can improve memory and cognitive function, shorten sleep latency, and increase non-rapid eye movement sleep time, prevent depression, improve long-term memory, and increase neuronal cell proliferation, down-regulate hypertension and decrease blood pressure [91,193]. GABA is also known to have an anti-diabetic effect, anti-cancer effect, anti-oxidant effect, anti-inflammatory effect, anti-nociceptive effect, anti-microbial effect, and anti-allergic effect [91,193].…”