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PHYTOTHERAPY RESEARCH Phytother. Res. 20, 758763 (2006) Published online 28 June 2006 in Wiley InterScience T. HONGRATANAWORAKIT AND G. BUCHBAUER (www.interscience.wiley.com) DOI: 10.1002/ptr.1950

Relaxing Effect of Ylang ylang Oil on Humans after Transdermal Absorption

Tapanee Hongratanaworakit1* and Gerhard Buchbauer2
1 2

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Srinakharinwirot University, Nakhon-nayok 26120, Thailand Department of Clinical Pharmacy and Diagnostics, Center of Pharmacy, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria

The aim of this study was to investigate the effects of ylang ylang oil (Cananga odorata, Annonaceae) on human physiological parameters and self-evaluation after transdermal absorption. Forty healthy volunteers participated in the experiments. Physiological parameters recorded were skin temperature, pulse rate, breathing rate and blood pressure. Self-evaluation was assessed by means of visual analog scales (VAS). The ylang ylang oil caused a signicant decrease of blood pressure and a signicant increase of skin temperature. At the behavioral level, subjects in the ylang ylang oil group rated themselves more calm and more relaxed than subjects in the control group. These ndings are likely to represent a relaxing effect of the ylang ylang oil and provide some evidence for the usage of the ylang ylang oil in aromatherapy such as causing a relief of depression and stress in humans. Copyright 2006 John Wiley & Sons, Ltd.
Keywords: physiological parameters; relaxing effect; behavioral evaluation; Cananga odorata.

INTRODUCTION In medicine interest in the usage of essential ylangylang oil (Cananga odorata, Annonaceae) as a therapeutically active agent has grown considerably. Especially in aromatherapy, ylang-ylang oil has been used as an antidepressant in cases of depression and nervousness as well as used for reducing the blood pressure in the case of hypertension. Clinical experience in aromatherapy suggests that benecial effects of essential oils are exerted by absorption of fragrance molecules through the skin. Topical application of essential oils in a carrier lotion has been reported by Macdonald (1995). This study demonstrated the enhancement of conventional methods of arthritic pain relief by the usage of essential oils. Wilkinson et al. (1999) reported on the evaluation of aromatherapy massage with essential oil in palliative care. In their studies, Roman chamomile oil helped to improve physical and psychological symptoms. Soden et al. (2004) showed that massage lavender oil caused a reduction in depression of patients in a palliative care unit. In addition, clinical aromatherapy on agitated behavior in dementia patients has been reported (Brooker et al., 1997; Ballard et al., 2002; Snow et al., 2004). Percutaneous absorption of lavender oil from massage oil was investigated by our group (Jaeger et al., 1992). They reported that the main component of lavender oil, i.e. linalool, could be detected in human blood samples 5 min after massage of the oil. Moreover, systemic absorption of topically applied monoterpene carvone from massage
* Correspondence to: Dr Tapanee Hongratanaworakit, Faculty of Pharmacy, Srinakharinwirot University, Rangsit-ongkharak Rd., Nakhon-nayok 26120, Thailand. E-mail: tapanee@swu.ac.th Contract/grant sponsor: Srinakharinwirot University, Thailand; contract/ grant number: 012/2005. Copyright 2006 John Wiley & Sons, Ltd. Copyright 2006 John Wiley & Sons, Ltd.

oil was studied (Fuchs et al., 1997; Jaeger et al., 2001). Their results showed that carvone penetrated the skin and exhibited a peak plasma concentration after about 30 min. Although many researchers attempted to prove the scientic effects of aromatherapy, most of the aromatherapy studies were not controlled studies and their results are therefore possibly biased and not scientic. In order to study the effects of fragrances or odors researchers have taken a great variety of approaches including measuring changes in physiological parameters, e.g. heart rate, breathing rate, blood pressure, eye movement, skin temperature and skin conductance, in physical performance and in mood (Bensa et al., 2002a, b, 2004; Brauchli et al., 1995; Haze et al., 2002; Ilmberger et al., 2001; Lorig and Schwartz, 1998; Miyazaki et al., 1991; Moss et al., 2003; Sugawara et al., 1998; Van et al., 1993). Although massage with essential oils is used increasingly for the improvement of the quality of life as well as for the relief of various symptoms in patients, scientic evaluation of the effects of transdermal administration of fragrances in healthy volunteers is rather scarce. Up to now, no experiments on the effects of ylang ylang oil on human physiological parameters and on behavioral patterns after transdermal administration have been carried out. Therefore, the main objective of the present study was to investigate the effects of this fragrance compound on physiological parameters as well as on behavioral responses in healthy humans following transdermal absorption.

MATERIALS AND METHODS Subjects and fragrance compound. Forty healthy volunteers aged between 19 and 48 years (mean age 23.05 4.10 years) took part in the experiments. Demographic
Received 27 758763 (2006) Phytother. Res. 20, December 2005 Revised 22 10.1002/ptr DOI: April 2006 Accepted 9 May 2006

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Table 1. Demographic data for the control group and the experimental group
Parameter Number of volunteers Sex (M:F) Height (mean SD) (cm) Weight (mean SD) (kg) Control group 20 12:8 172.75 6.01 159.91 4.81 63.12 5.64 55.66 8.73 Ylang ylang group 20 12:8 175.43 5.77 160.25 3.77 64.43 4.44 54.75 6.29

Male Female Male Female

data for the control group and the experimental group are presented in Table 1. Subjects were tested in individual sessions and randomly assigned to either the control group or the ylang ylang oil group. Each group consisted of 20 subjects. They were fully briefed and gave written informed consent to all aspects of the study (Srinakharinwirot University Ethics Commission permissions). The ylang ylang oil (fraction II) was obtained by steam distillation of the dry, fresh picked owers of Cananga odorata (DC.) Hook. f. et Thoms., Annonaceae. The oil was identied by GC and GC/ MS. The oil mainly contains methyl benzoate (34.00%), 4-methylanisole (19.82%) and benzyl benzoate (18.97%). Fragrance administration. In the experimental group, 1 mL of a 20% (w/w) solution of ylang ylang oil in sweet almond oil was applied to the skin of the lower abdomen of each subject and the subjects massaged the oil into the skin by themselves for 5 min. Afterwards the massage area was covered with a plastic lm in order to prevent evaporation of the oil. In the control group, 1 mL of the placebo substance, i.e. pure sweet almond oil, was used. In both groups subjects were supplied with pure air by breathing masks (inhalation set for adult, product no.1500004020, B+P Beatmungsprodukte GmbH, Neunkirchen, Germany) in order to eliminate any olfactory stimulation by nose or mouth. Experimental design. The experimental design has been previously used by our group (Heuberger et al., 2001; Hongratanaworakit et al., 2004; Hongratanaworakit and Buchbauer, 2004a, 2005). One session consisted of two trials of 20 min each. At the beginning and at the end of each trial, behavioral responses were assessed by visual analogue scales (VAS). Physiological parameters were recorded continuously during each trial. In the rst trial, which served as a control for inuences of the experimental set-up, the placebo substance was administered to all subjects. In the second trial the placebo was again administered to the control group, whereas in the experimental group the appropriate fragrance was administered. Procedure. All experiments were conducted in a bright and quiet room. The ambient temperature was 2426 C. Upon arrival, the volunteers were interviewed about their personal data. In addition, they were asked about the rating of behavioral responses. After completion of the interview and the rating scales, systolic and diastolic blood pressure (SBP, DBP) were measured. Subsequently, the subjects were informed about the proceedings. Afterwards subjects were seated in a semi-reclined
Copyright 2006 John Wiley & Sons, Ltd.

position, providing easy access to attach the electrodes. Electrodes were attached on suitable positions. The inhalation set was tted to the volunteers face to cover the nose and mouth. The oxygen was then supplied directly. The oil or the placebo substance were administered as described above. Then, the recording of the physiological parameters was started. After completion of the rst trial, the subjects were asked to rate the rating scales. The SBP and DBP were measured at the end of the rst trial. This procedure was repeated in the second trial. At the end of each trial, the subjects were asked if they had smelled any odor during the experiment. All subjects stated that they did not smell any odor during the experiment. Acquisition of physiological parameters and statistical analysis. Breathing rate (BR), pulse rate (PR) and skin temperature (ST) were measured using Power Lab/4SP hardware (ADInstruments, Inc., NSW, Australia). The sampling rate was 100 Hz. Systolic and diastolic blood pressure (SBP and DBP) were determined by sphygmomanometry using an automated system (Digital Electronic Model DS-155E, Japan). Details of the recording system and procedure have been described elsewhere (Heuberger et al., 2001; Hongratanaworakit et al., 2004; Hongratanaworakit and Buchbauer, 2004a, 2005). VAS, i.e., relaxation, vigor, calmness, attentiveness, mood and alertness, were used to assess behavioral responses. All statistical calculations and data analyses were performed with the Statistical Package for the Social Sciences (SPSS version 11.5). The effects of fragrances on physiological parameters and ratings of behavioral responses were determined by MannWhitney U-test analysis of variances.

RESULTS Physiological parameters The mean and SEM of physiological parameters of the control group and the experimental group are presented in Table 2. The SBP of subjects in the control group increased at the end of the second trial compared with the end of the rst trial. In contrast, the SBP of subjects in the ylang ylang oil group decreased at the end of the second trial compared with the end of the rst trial. The difference scores of SBP between the second trial and the rst trial for the control group and the ylang ylang oil group are shown in Fig. 1. Comparison of these difference scores revealed a signicantly larger decrease of SBP in the ylang ylang oil group than in the control group (p = 0.012). The DBP of subjects in
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Table 2. Mean and SEM of physiological parameters of the control group and the experimental group
Control (mean SEM) Trial 1 Systolic BP Diastolic BP Skin temperature Breathing rate Pulse rate 99.35 58.06 36.98 17.00 68.07 2.79 1.95 0.20 0.84 1.76 Trial 2 104.82 63.72 36.55 16.96 66.20 3.89 2.37 0.23 0.90 1.84 Ylang ylang (mean SEM) Trial 1 107.18 58.56 36.80 17.10 70.50 1.96 1.22 0.19 1.34 3.45 Trial 2 106.06 60.50 36.97 17.62 66.25 2.14 1.48 0.15 1.81 2.42

Figure 1. The difference scores and SEM of systolic blood pressure for the control group and the ylang ylang oil group.

Figure 2. The difference scores and SEM of diastolic blood pressure for the control group and the ylang ylang oil group.

the control group increased at the end of the second trial compared with the end of the rst trial. While the DBP of subjects in the ylang ylang oil group only marginally changed at the end of the second trial compared with the end of the rst trial. The difference scores of DBP between the second trial and the rst trial for the control group and the ylang ylang oil group are shown in Fig. 2. Comparison of these difference scores revealed a signicantly smaller increase of DBP in the ylang ylang oil group than in the control group (p = 0.033). The ST of subjects in the control group decreased in the second trial compared with the rst trial. In contrast, the ST of subjects in the ylang ylang oil group increased in the second trial compared with the rst trial. The difference scores of ST between the second trial and the rst trial for the control group and the ylang ylang oil group are shown in Fig. 3. Comparison of these difference scores revealed a signicantly larger increase of ST in the ylang ylang oil group than in the control group (p = 0.037). No signicant effects of the ylang ylang oil on BR and on PR were found (p > 0.05 for all). Behavioral responses The mean and SEM of behavioral responses of the control group and the experimental group are presented
Copyright 2006 John Wiley & Sons, Ltd.

Figure 3. The difference scores and SEM of skin temperature for the control group and the ylang ylang oil group.
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Table 3. Mean and SEM of behavioral responses of the control group and the experimental group
Control (mean SEM) Trial 1 Attentiveness Alertness Calmness Relaxation Mood Vigor 25.50 40.00 20.82 28.28 32.47 47.45 3.10 3.00 2.63 3.77 3.64 3.38 Trial 2 26.50 39.65 25.65 29.89 36.41 45.65 3.47 3.83 3.80 3.82 3.94 3.86 Ylang ylang (mean SEM) Trial 1 28.10 35.93 28.29 31.88 33.18 45.40 4.45 4.71 4.86 5.76 3.94 5.31 Trial 2 24.38 33.83 18.29 18.76 26.85 40.14 3.04 4.32 2.53 2.55 3.24 4.30

Figure 4. The difference scores and SEM of subjective calmness for the control group and the ylang ylang oil group.

Figure 5. The difference scores and SEM of subjective relaxation for the control group and the ylang ylang oil group.

in Table 3. Subjects in the control group felt less calm at the end of the second trial compared with the end of the rst trial. In contrast, subjects in the ylang ylang oil group judged themselves more calm at the end of the second trial compared with the end of the rst trial. The difference scores of subjective calmness between the second trial and the rst trial for the control group and the ylang ylang oil group are shown in Fig. 4. Comparison of these difference scores revealed a signicant increase of subjective calmness in the ylang ylang oil group compared with the control group ( p = 0.022). In addition, subjects in the control group felt less relaxed at the end of the second trial as compared to the end of the rst trial. On the other hand, subjects in the ylang ylang oil group judged themselves more relaxed at the end of the second trial compared with the end of the rst trial. The difference scores of subjective relaxation between the second trial and the rst trial for the control group and the ylang ylang oil group are shown in Fig. 5. Comparison of these difference scores revealed a signicant increase of subjective relaxation in the ylang ylang oil group as compared to the control group (p = 0.021). No signicant effects of the ylang ylang oil on subjective alertness, attentiveness, mood or vigor were found (p > 0.05 for all).
Copyright 2006 John Wiley & Sons, Ltd.

DISCUSSION In the present investigation ylang ylang oil was administered transdermally to healthy subjects. Physiological parameters, i.e. blood pressure, pulse rate, breathing rate and skin temperature, were recorded as indicators of the arousal level of the autonomic nervous system (ANS). In addition, subjects had to rate their mental and emotional condition in terms of relaxation, vigor, calmness, attentiveness, mood and alertness in order to assess subjective behavioral arousal. The ylang ylang oil caused a signicant decrease of blood pressure. Since blood pressure is determined by the activity of the sympathetic branch of the ANS, a decrease of blood pressure shows a decrease of sympathetic tone, i.e. a decrease of physiological arousal. A signicantly larger increase of skin temperature in the ylang ylang oil group compared with the control group was found. Skin temperature is controlled indirectly by the sympathetic division of the ANS via the contraction or relaxation of the smooth muscles which surround the blood vessels and regulate blood supply to distinct skin areas. When these muscles are contracted skin temperature is lower because less blood reaches there. On the other hand,
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when these muscles are relaxed skin temperature is higher because more blood is supplied there. Therefore, the increase of skin temperature in the ylang ylang oil group indicates a decrease of ANS arousal. At the behavioral level, subjects in the ylang ylang oil group rated themselves more calm and more relaxed than subjects in the control group. This nding points towards a decrease of arousal in terms of self-evaluation. Transdermal absorption of ylang ylang oil reduced the level of arousal of the ANS and led to deactivation at the behavioral level, i.e. subjects felt more calm and more relaxed than before the administration of the oil. Thus, the effects of ylang ylang oil by means of percutaneous administration may be characterized by the concept of relaxation which has also been described for the sandalwood essential oil (Hongratanaworakit et al., 2004). However, our previous study (Hongratanaworakit and Buchbauer, 2004a) reported that inhalation of ylang ylang oil reduced the level of arousal of the ANS but led to activation at the behavioral level, i.e. subjects felt more attentive and more alert than before the administration of the oil. Thus, the effects of ylang ylang oil by means of inhalation may be characterized by the concept of harmonization rather than relaxation/sedation. All our ndings

indicate that the differential effects of the essential oils depend on the mode/route of administration. Both pharmacological and psychological effects are active simultaneously when the oils are administered by means of inhalation and olfactory processing occurs. In contrast, percutaneous administration gives evidence of the pure pharmacological effect and exclusion of olfactory processing. Therefore, in order to differentiate between pharmacological and psychological effects of fragrances, a subjective evaluation of the odors must be prevented (Heuberger et al., 1999; Heuberger et al., 2001; Hongratanaworakit et al., 2000; Hongratanaworakit and Buchbauer, 2004b, 2005; Ilmberger et al., 2001). In conclusion, our investigation is likely to represent a relaxing effect of ylang ylang oil and provide some evidence for the usage of ylang ylang oil in medicines such as causing a reduction of blood pressure or for the relief of depression and stress in humans.

Acknowledgements
This work was supported by grants from Srinakharinwirot University, Thailand. The author is grateful to Dr E. Heuberger, University of Vienna, Austria, for experimental designs suggestion.

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Phytother. Res. 20, 758763 (2006) DOI: 10.1002/ptr