Identification of isobutyl angelate, isoamyl angelate and 2‐methylbutyl isobutyrate as active constituents in Roman chamomile essential oil that promotes mouse ambulation

Abstract

Roman chamomile (Chamaemelum nobile or Anthemis nobilis) has traditionally been used for health care, health maintenance and medicinal purposes, and the essential oil obtained from the flowers is used as a basic ingredient for aromatherapy. Roman chamomile essential oil (CHA) produces psychostimulant‐like effects, such as the ambulation‐promoting effect, on mouse behaviour. However, mechanisms underlying the effects of CHA remain unclear. The present study aimed to identify the constituents responsible for the ambulation‐promoting effect of CHA and to elucidate a possible neuronal mechanism. GC/MS analysis revealed that isobutyl angelate, isoamyl angelate and 2‐methylbutyl isobutyrate were the major constituents of CHA. These compounds significantly promoted mouse ambulation, and were thus identified as the major active constituents for the ambulatory effect of CHA. The ambulatory effects were attenuated by chlorpromazine and haloperidol, suggesting that the neurotransmitter dopamine is involved in the ambulation‐promoting effects of these constituents similar to already‐known psychostimulants. The results suggest that CHA can change a mental condition, at least in part, through the CNS effects of the constituents identified in the current study. The results also suggest that mental effects of CHA are largely different from those of other Roman chamomile preparations due to the composition difference.

Effects of essential oils on central nervous system: Focus on mental health

“…Moreover, calming effects are also produced by increasing serotonin levels while decreasing glucocorticoids like in the case of ylang‐ylang EO (Zhang, Zhang, Feng, & Yao, 2016; Zhang, Zhang, Feng, & Yao, 2018). Furthermore, it has been demonstrated experimentally that other EOs like rosemary (Moss, Cook, Wesnes, & Duckett, 2003; Villareal et al, 2017), clary sage (Seol et al, 2010), and roman chamomile (Umezu, 2012; Umezu, Sano, Hayashi, Yoshikawa, & Shibata, 2017) stimulate the DAnergic system resulting in psychostimulant and cognitive‐enhancer effects. Additionally, bergamot (Morrone et al, 2007), lemongrass (Costa et al, 2011) and lavender (Guillmain, Rousseau, & Delaveau, 1989) EOs can exert its anxiolytic effects by activating the GABAergic system.…”

“…Although diverse extracts of roman chamomile are well‐known for their anxiolytic and sedative activities, a recent study has shown that the EO produced by steam distillation has psychostimulant effects. Umezu et al, 2017 identified and studied the effects of Roman chamomile EO constituents on the CNS in male mice by using the tilting type ambulometer test (Table 2). Isobutyl angelate, isoamyl angelate and 2‐methylbutyl isobutyrate were identified as the major active constituents responsible for the ambulatory‐promoting effects of roman chamomile, which accounted for about 75% of the EO.…”

“…Isobutyl angelate, isoamyl angelate, 2‐methylbutyl isobutyrate and 2‐methylbutyl angelate have been previously detected in Roman chamomile EO (Omidbaigi et al, 2003; Rossi, Melegari, Bianchi, Albasini, & Vampa, 1988). Umezu et al, 2017 compared the effects produced by Roman chamomile EO with a mix of isobutyl angelate, isoamyl angelate and 2‐methylbutyl isobutyrate in male mice. The mixture did not fully replicate the effect of the EO suggesting that the minor components also made a contribution toward the total effect.…”

“…The lack of the flavonoid, 7,4′ ‐trihydroxyflavone (apigenin) in this Roman chamomile EO could explain the absence of a specific calming effect. Furthermore, apigenin is known to significantly contribute to the sedative and anxiolytic effects of Roman chamomile aqueous extracts by binding to GABA A receptors (Viola et al, 1995; Umezu et al, 2017). Furthermore, Umezu (2012) had previously showed the stimulant‐like effects of Roman chamomile EO and peppermint EO in the CNS by using a discrete shuttle‐type conditioned avoidance task in male mice.…”

Simultaneous blood and brain microdialysis in a free-moving mouse to test blood-brain barrier permeability of chemicals

“…GC/MS analysis was performed using an MStation JMS-700KII mass spectrometer (JEOL, Tokyo, Japan) equipped with a 6890 N gas chromatograph (GC; Agilent Technologies, Santa Clara, CA) [ 19 ]. The GC was fitted with a fused silica capillary column (DB-5MS; 0.25 mm inner diameter, 30 m) coated with 5% phenyl methyl silica.…”