Advances of ionic liquid-based nanohybrids for biomedical applications.

Ionic liquids (ILs) are composed of asymmetric cationic and anionic moieties and are used as green solvents. Their non-toxic nature, favorable biocompatibility and adjustable structure facilitate wide biomedical applications. ILs promote the generation of various nanohybrids that exhibit multiple functions and novel/improved properties with respect to their precursors. Generally, nanostructures have a large specific surface area and abundant functional groups which enable loading and incorporation of ILs through physical interactions or chemical bonding. According to their main skeleton structures, IL-based nanohybrids may be divided into five categories, i.e., poly(ionic liquid)s (PILs), IL-inorganic nanohybrids, IL-metal organic framework nanohybrids (IL-MOF nanohybrids), ILs/carbon materials and ionic materials. These IL-based nanohybrids exhibit various specific features, including thermal responsive behavior, metal chelating, photothermal conversion and antibacterial capabilities. Taking advantage of these characteristics, IL-based nanohybrids may overcome the shortcomings of conventional medicines/drugs and exhibit promising prospects in biomedicine to facilitate controlled drug release, bactericidal treatment and thermotherapy. The present review presents the state-of-the-art progress made in the studies of IL-based nanohybrids in terms of their classifications, structure characteristics, versatile functionalities and biomedical and pharmaceutical applications. The challenges and future perspectives in the developments and applications of IL-based nanohybrids in biomedicine are discussed.

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

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.

Identification of both GABAA receptors and voltage-activated Na(+) channels as molecular targets of anticonvulsant α-asarone.

Alpha (α)-asarone, a major effective component isolated from the Chinese medicinal herb Acorus tatarinowii, is clinically used as medication for treating epilepsy, cough, bronchitis, and asthma. In the present study, we demonstrated that α-asarone targets central nervous system GABAA receptor as well as voltage-gated Na(+) channels. Using whole-cell patch-clamp recording, α-asarone inhibited spontaneous firing of output neurons, mitral cells (MCs), in mouse olfactory bulb brain slice preparation and hyperpolarized the membrane potential of MCs. The inhibitory effect of α-asarone persisted in the presence of ionotropic glutamate receptor blockers but was eliminated after adding a GABAA receptor blocker, suggesting that GABAA receptors mediated the inhibition of MCs by α-asarone. This hypothesis was supported by the finding that α-asarone evoked an outward current, but did not influence inhibitory postsynaptic currents (IPSCs). In addition to inhibiting spontaneous firing, α-asarone also inhibited the Nav1.2 channel, a dominant rat brain Na(+) channel subtype. The effects of α-asarone on a defined Nav1.2 were characterized using transfected cells that stably expressed the Nav1.2 channel isoform. α-Asarone displayed strong tonic inhibition of Nav1.2 currents in a concentration- and membrane potential-dependent fashion. α-Asarone reduced channel availability in steady-state inactivation protocols by enhancing or stabilizing Na(+) channel inactivation. Both Na(+) channel blockade and activation of GABAA receptors provide a possible mechanism for the known anti-epileptic effects of α-asarone. It also suggests that α-asarone could benefit patients with cough possibly through inhibiting a Na(+) channel subtype to inhibit peripheral and/or central sensitization of cough reflexes.