Anxiolytic effects of essential oils may involve anti-oxidant regulation of the pro-oxidant effects of ascorbate in the brain.

Essential oils (EOs) absorbed via inhalation are consistently reported to produce anxiolytic effects. The underlying neurochemical mechanisms, however, are not well understood. High concentrations of ascorbate in the human brain (~10 mM in neurons) implicates this compound as a key signaling molecule and regulator of oxidative stress. In this study, we demonstrate the significant in vitro capacity of ascorbate to produce H2O2 in the presence of oxygen at physiological pH values, peaking at ~400 µM for ascorbate levels of 1.0 mg/mL (5.6 mM). In comparison, individual EOs and selected neurotransmitters at similar concentrations produced <100 µM H2O2. Systematic studies with binary and ternary mixtures containing ascorbate indicated that EOs and neurotransmitters could variably enhance (pro-oxidant, POX) or suppress (anti-oxidant, AOX) the production of H2O2 versus the ascorbate control, depending on the concentration ratios of the components in the mixture. Moreover, the AOX/POX chemistry observed with binary mixtures did not necessarily predict effects with ternary mixtures, where the POX ascorbate chemistry tended to dominate. A model is proposed to account for the ability of compounds with electron-donating capacity to catalytically regenerate ascorbate from intermediate oxidized forms of ascorbate, thus driving H2O2 production and exerting a net POX effect; whilst compounds that irreversibly reacted with oxidized forms of ascorbate suppressed the production of H2O2 and produced an overall AOX effect. Since the anxiolytic effects of different EOs, including extracts of Lavendula angustifolia (lavender) and Salvia rosmarinus (rosemary), were associated with AOX regulation of H2O2 production by ascorbate, it can be concluded that these anxiolytic effects are potentially related to the AOX properties of EOs. In contrast, EOs driving POX effects (eg, Junipenus communis (Juniper) berry EO) are proposed to be more useful for their potential anti-microbial or cancer cytotoxic applications.