- Email: [email protected]
Research reports
The International Journal of Aromatherapy (2005) 15, 153–156
The International Journal of
Aromatherapy intl.elsevierhealth.com/journals/ijar
Research reports B. Harris
*
‘Au village’, 83840 La Martre, Provence, France
Reduction of tumour smell Escherichia coli or anaerobic bacteria often infect superficial malignant necrotic ulcers and cause an intense malodour, especially when situated within the oral or nasal cavity. The standard treatment is clindamycin and chlorophyll with Betadine solution for topical disinfection. However, this combination only slightly reduces the smell and the patients’ quality of life deteriorates. They are often segregated from other patients due to the odour and become socially isolated when relatives become reluctant to visit. The application of pleasant-smelling antibacterial essential oils to malodorous advanced squamous cell carcinomas of the head and neck has been investigated by Warnke et al. (2004). The ulcers of 25 patients were rinsed twice daily with a mixture of tea tree, grapefruit and eucalyptus essential oils (MegabacÒ). The mixture could also be administered easily via a pump-spray container. Patients also received the standard medication minus topical Betadine. It was found that the malodour from the necrotic ulcers receded entirely after 2–3 days of treatment with the essential oils and pus secretion and signs of super-infection were often significantly reduced. Adverse effects of the treatment were a bitter taste and a slight burning sensation when the mixture was applied to the intraoral mucosa, but these were well accepted by the patients.
* Tel./fax: +33 494 84 29 93. E-mail address: [email protected].
Allergic reactions to the essential oils were not observed. Some patients experienced pain relief after the rinsing of their necrotic cavities; an effect that was attributed to the anaesthetic properties of eucalyptus essential oil. The main positive outcome of treatment was that the patients were returned to regular wards and experienced improved social interactions with relatives, friends and other patients. Some patients even returned home with essential oil treatment continued by local doctors or relatives. It was concluded that the inexpensive, easily administered essential oils should be introduced into modern palliative care.
Anti-MRSA wound care In burns cases, 75% of deaths are linked to wound infections, and adverse effects from infection include delayed healing, increased depth of burn and graft failure. Staphylococcus aureus infects about 30% of burns and outbreaks of methicillinresistant S. aureus create major problems in burns and intensive care units. Resistance to one of the few remaining effective systemic antibiotics, vancomycin, has been reported and total antibioticresistant strains may appear in the near future. To prevent infection, topical antimicrobial therapy is most important and in burns patients, Flamazineä is most frequently used as a prophylactic agent. It cannot remove bacteria from the environment or prevent carriage in patients and does not always penetrate the wound. Alternative
0962-4562/$ - see front matter c 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijat.2005.07.001
154 treatments for MRSA are being sought and a UK team (Edwards-Jones et al., 2004) have tested essential oils using an in vitro dressing model. The essential oils of Melaleuca alternifolia (tea tree), Pogostemon cablin (patchouli), Lavandula angustifolia (lavender) and Pelargonium graveolens (geranium) and an antibacterial commercial grapeseed extract (Citricidalä) were used against three S. aureus strains, two of which were methicillin-resistant. To assess their antibacterial activity, 20 ll of individual oils, the extract, or their combinations (50:50) were added to paper discs, which were either placed onto seeded agar plates (direct contact) or suspended above the plates (vapour contact). After incubation, zones of inhibition were measured. Essential oils and combinations that demonstrated antibacterial activity were placed onto the central area of the outer Gamgee or gauze dressing layer of a four-layer dressing model, which was then placed over a seeded agar plate. Modifications were made to the primary layer by including or excluding Flamazineä, and using reduced adherence dressings of Telfa Clearä or Jelonetä or both. After incubation, zones of inhibition were measured. With direct contact, tea tree essential oil gave the largest zones of inhibition against MRSA, with the other oils and Citricidalä also inhibiting the three strains of staphylococcus but to a lesser degree. The non-MRSA strain was most affected. Of the pair combinations, patchouli and tea tree, lavender and geranium, lavender and tea tree, grapefruit and tea tree and geranium and tea tree produced increased zones of inhibition against the non-MRSA strain but not the MRSA strains. Against the latter, lavender and tea tree and Citricidalä and tea tree showed decreased activity. With vapour contact, only tea tree demonstrated a limited effect against one strain of MRSA. The non-MRSA strain was most susceptible to patchouli, geranium and tea tree but not to lavender or the grapefruit seed extract. The combinations of patchouli and tea tree, Citricidalä and geranium and Citricidalä and tea tree produced increased zones of inhibition against the MRSA strains, whereas the single products gave no or very small zones. In the dressing model, only the most effective oil combinations for each strain were used. In the presence of Flamazineä, no inhibition occurred, whereas in its absence zones of inhibition were produced. This was attributed to the thick coating of cream preventing the volatile components from reaching the bacteria. The MRSA strains
B. Harris were most susceptible to a combination of geranium and Citricidalä; the non-MRSA strain was most susceptible to a combination of geranium and tea tree. When Telfa Clearä was used as the primary layer instead of Jelonetä, the zones of inhibition were increased; the impregnated paraffin of the latter may have affected vapour penetration. In the dressing model, the oils were placed in the centre of either the Gamgee or the gauze layer, there being little difference in the size of the zones of inhibition produced. This means that if essential oils were to be used, it would be possible to leave the inner dressing in place and only change the outermost dressing and/or re-impregnate with oils. Thus the wound would not be disturbed and antibacterial therapy could be maintained. It was concluded that the vapour from essential oil combinations can inhibit MRSA and may prove useful in eradicating the bacteria from wounds.
Long-term effects of lemon Despite the known effects of essential oils, there is still no definitive picture of the physiological changes that occur during olfactory stimulation, especially with regard to nociception and pain. Researchers had already shown that the acute exposure of rats to lemon essential oil produced sex differences in behavioural and neuronal responses. The same Italian group (Ceccarelli et al., 2004) examined the effects of long term lemon exposure on behavioural, hormonal and neuronal parameters. Eighty rats were divided into control and test groups of equal sexes. In the test group 150 ll of lemon essential oil was added to the animal’s cage every three days, for one week before the beginning of the tests and continuing throughout the tests and ending on day 12. The tests consisted of behaviours in the elevated plus-maze, thermal pain thresholds in a plantar test and spontaneous and nociceptive responses induced by a subcutaneous injection of a stimulus or a sham injection. Lastly, b-endorphin levels were measured in the hypothalamus and periaqueductal gray matter (PAG) areas of the brain. Blood samples were collected to determine corticosterone plasma levels. In both sexes, long-term exposure to lemon essential oil increased anxiety behaviour in the maze test and the thermal pain threshold was increased. The PAG b-endorphin content was lower in both sexes as compared to the control group.
Research reports One pathway to modify pain input is the descending aminergic pathway originating from the PAG and acting at the spinal cord level. It would appear that the essential oil affected this brain area, probably inducing a greater release of b-endorphin to modulate the nociceptive input. During prolonged nociception, sex-specific effects were noted in that females demonstrated antinociception whilst males did not. Hypothalamic b-endorphin was decreased in males but increased in females. As the hypothalamus is the site of b-endorphin synthesis, it was postulated that the essential oil-induced decrease of b-endorphin in males produced a lower reserve of endorphin that was less likely to affect prolonged nociception. Unlike the b-endorphin in the PAG, that of the hypothalamus is also involved in many other circuits, including those modulating arousal and attention. It was thought that the olfactory stimulation of the essential oil stimulated a female-specific circuit of the motor system. Corticosterone levels (that evaluate the degree of arousal of the hypothalamo-pituitary-adrenal axis) were greatly decreased by prolonged essential oil exposure in both injected and sham-injected animals. This was attributed to an adaptation of the corticosterone response, as caused by exposure to some types of stressors. In addition to the activated stress-like pathways able to produce an increase in the thermal pain threshold, the olfactory stimulation also ‘masked’ some of the negative aspects of inflammatory nociception, but only in females. It was concluded that activation of the olfactory-hippocampal pathway was sufficient to affect behaviour and nociception.
Antiviral melissa Infection with Herpes simplex virus (HSV) can be treated with antiviral drugs that interfere with virus-specific enzymes, e.g. fluorothymidine, but due to their cytotoxic effects, they are not widely used. A less cytotoxic drug, acyclovir, is the preferred treatment although it has been reported to be inefficient in treating genital herpes caused by HSV-2. In addition, HSV-2 has also been found to acquire resistance to these drugs. For these reasons, the search for new anti-HSV drugs is on the increase and those derived from plants are especially promising. A number of previous studies had demonstrated the antiviral properties of Melissa officinalis extracts on a number of viruses including HSV; the
155 activity was attributed to a non-tannin polyphenolic fraction, but the essential oil itself was not tested. A Turkish study (Allahverdiyev et al., 2004) has evaluated the in vitro antiviral activity of the essential oil against HSV-2. The experiment was carried out on human larynx epidermoid carcinoma cells (Hep-2 cell line) infected with HSV-2. The cytotoxicity of the essential oil was determined by adding various concentrations of the oil (25–200 ll/ml) to cell cultures and allowing them to grow for 48 h before examination. The highest noncytocidal concentration was found to be 100 ll/ml and so this concentration was used in the determination of antiviral activity. The essential oil was found to reduce the viral infectivity of three different infective doses of HSV-2. Acyclovir was used as the control. The virus titre was estimated from cytopathogenicity and expressed as 50% tissue culture infectious dose per millilitre (TCID50). At 1 and 10 TCID50, the antiviral effect of the essential oil was not statistically different from that of acyclovir, but at 100TCID50, the effect was lower than that of acyclovir. The inhibition of proliferation of HSV-2 by the essential oil varied inversely with the concentration of the virus. It was concluded that the essential oil of Turkish M. officinalis contained an anti-HSV-2 component.
Anticholinesterase terpenoids Enhancement of the cholinergic deficit associated with Alzheimer’s disease is currently based on the inhibition of the enzyme acetylcholinesterase (AChE). Previous research had shown that the essential oil of Salvia lavandulaefolia possessed in vitro and in vivo anticholinesterase activity. This activity was thought to be due to a synergistic activity within the oil rather than from a single inhibitor, and so a UK study (Savelev et al., 2003) examined the individual and combined activities of a number of components. Their work was based on the hypothesis that the activity of the essential oil was greater than the combined activity of individual components in their naturally occurring ratios. The components investigated were 1,8-cineole, camphor, a-pinene, b-pinene, borneol, caryophyllene oxide, linalol and bornyl acetate, ranging from 26.8% to 0.7% concentration in the essential oil, respectively. The components were initially divided into those that reached 50% inhibition of AChE and those that
156 were less potent. The IC50 value of the essential oil was not significantly different from that of 1,8-cineole, which itself was marginally less than the IC50 value of a-pinene. The other components had significantly less anticholinesterase activity. On the basis of their naturally occurring concentrations in the essential oil, the components were assessed in combinations for their anticholinesterase activity. As 1,8-cineole accounted for half of the activity of the essential oil, it was considered as the main agent that could show synergy with other components. A minor synergy was seen with 1,8-cineole/ a-pinene and 1,8-cineole/caryophyllene oxide combinations whereas a combination of 1,8-cineole and camphor was significantly antagonistic. In combinations of the remaining six components, synergism was or was not determined, according to the method of analysis employed. It was thus found that the inhibitory activity of the essential oil towards AChE resulted from a complex interaction between component terpenes involving both synergistic and antagonistic responses. Based on the findings, it was suggested
B. Harris that the essential oil of Salvia fruticosa may possess a higher anticholinesterase activity because it contained 1,8-cineole up to 75% and a relatively low camphor content.
References Allahverdiyev A, Duran N, Ozguven M, Koltas S. Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2. Phytomed 2004;11: 657–61. Ceccarelli I, Lariviere WR, Fiorenzani P, Sacerdote P, Aloisi AM. Effects of long-term exposure of lemon essential oil odor on behavioral, hormonal and neuronal parameters in male and female rats. Brain Res 2004;1001:78–86. Edwards-Jones V, Buck R, Shawcross SG, Dawson MM, Dunn K. The effect of essential oils on methicillin-resistant Staphylococcus aureus using a dressing model. Burns 2004;30:772–7. Savelev S, Okello E, Perry NSL, Wilkins RM, Perry EK. Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharmacol Biochem Behav 2003;75:661–8. Warnke PH, Ac ¸il Y, Springer IN, Sherry E, Reynolds M, Russo RAJ, et al. Tumor smell reduction with antibacterial essential oils. Cancer 2004;100:879–80.
The International Journal of
Aromatherapy intl.elsevierhealth.com/journals/ijar
Research reports B. Harris
*
‘Au village’, 83840 La Martre, Provence, France
Reduction of tumour smell Escherichia coli or anaerobic bacteria often infect superficial malignant necrotic ulcers and cause an intense malodour, especially when situated within the oral or nasal cavity. The standard treatment is clindamycin and chlorophyll with Betadine solution for topical disinfection. However, this combination only slightly reduces the smell and the patients’ quality of life deteriorates. They are often segregated from other patients due to the odour and become socially isolated when relatives become reluctant to visit. The application of pleasant-smelling antibacterial essential oils to malodorous advanced squamous cell carcinomas of the head and neck has been investigated by Warnke et al. (2004). The ulcers of 25 patients were rinsed twice daily with a mixture of tea tree, grapefruit and eucalyptus essential oils (MegabacÒ). The mixture could also be administered easily via a pump-spray container. Patients also received the standard medication minus topical Betadine. It was found that the malodour from the necrotic ulcers receded entirely after 2–3 days of treatment with the essential oils and pus secretion and signs of super-infection were often significantly reduced. Adverse effects of the treatment were a bitter taste and a slight burning sensation when the mixture was applied to the intraoral mucosa, but these were well accepted by the patients.
* Tel./fax: +33 494 84 29 93. E-mail address: [email protected].
Allergic reactions to the essential oils were not observed. Some patients experienced pain relief after the rinsing of their necrotic cavities; an effect that was attributed to the anaesthetic properties of eucalyptus essential oil. The main positive outcome of treatment was that the patients were returned to regular wards and experienced improved social interactions with relatives, friends and other patients. Some patients even returned home with essential oil treatment continued by local doctors or relatives. It was concluded that the inexpensive, easily administered essential oils should be introduced into modern palliative care.
Anti-MRSA wound care In burns cases, 75% of deaths are linked to wound infections, and adverse effects from infection include delayed healing, increased depth of burn and graft failure. Staphylococcus aureus infects about 30% of burns and outbreaks of methicillinresistant S. aureus create major problems in burns and intensive care units. Resistance to one of the few remaining effective systemic antibiotics, vancomycin, has been reported and total antibioticresistant strains may appear in the near future. To prevent infection, topical antimicrobial therapy is most important and in burns patients, Flamazineä is most frequently used as a prophylactic agent. It cannot remove bacteria from the environment or prevent carriage in patients and does not always penetrate the wound. Alternative
0962-4562/$ - see front matter c 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijat.2005.07.001
154 treatments for MRSA are being sought and a UK team (Edwards-Jones et al., 2004) have tested essential oils using an in vitro dressing model. The essential oils of Melaleuca alternifolia (tea tree), Pogostemon cablin (patchouli), Lavandula angustifolia (lavender) and Pelargonium graveolens (geranium) and an antibacterial commercial grapeseed extract (Citricidalä) were used against three S. aureus strains, two of which were methicillin-resistant. To assess their antibacterial activity, 20 ll of individual oils, the extract, or their combinations (50:50) were added to paper discs, which were either placed onto seeded agar plates (direct contact) or suspended above the plates (vapour contact). After incubation, zones of inhibition were measured. Essential oils and combinations that demonstrated antibacterial activity were placed onto the central area of the outer Gamgee or gauze dressing layer of a four-layer dressing model, which was then placed over a seeded agar plate. Modifications were made to the primary layer by including or excluding Flamazineä, and using reduced adherence dressings of Telfa Clearä or Jelonetä or both. After incubation, zones of inhibition were measured. With direct contact, tea tree essential oil gave the largest zones of inhibition against MRSA, with the other oils and Citricidalä also inhibiting the three strains of staphylococcus but to a lesser degree. The non-MRSA strain was most affected. Of the pair combinations, patchouli and tea tree, lavender and geranium, lavender and tea tree, grapefruit and tea tree and geranium and tea tree produced increased zones of inhibition against the non-MRSA strain but not the MRSA strains. Against the latter, lavender and tea tree and Citricidalä and tea tree showed decreased activity. With vapour contact, only tea tree demonstrated a limited effect against one strain of MRSA. The non-MRSA strain was most susceptible to patchouli, geranium and tea tree but not to lavender or the grapefruit seed extract. The combinations of patchouli and tea tree, Citricidalä and geranium and Citricidalä and tea tree produced increased zones of inhibition against the MRSA strains, whereas the single products gave no or very small zones. In the dressing model, only the most effective oil combinations for each strain were used. In the presence of Flamazineä, no inhibition occurred, whereas in its absence zones of inhibition were produced. This was attributed to the thick coating of cream preventing the volatile components from reaching the bacteria. The MRSA strains
B. Harris were most susceptible to a combination of geranium and Citricidalä; the non-MRSA strain was most susceptible to a combination of geranium and tea tree. When Telfa Clearä was used as the primary layer instead of Jelonetä, the zones of inhibition were increased; the impregnated paraffin of the latter may have affected vapour penetration. In the dressing model, the oils were placed in the centre of either the Gamgee or the gauze layer, there being little difference in the size of the zones of inhibition produced. This means that if essential oils were to be used, it would be possible to leave the inner dressing in place and only change the outermost dressing and/or re-impregnate with oils. Thus the wound would not be disturbed and antibacterial therapy could be maintained. It was concluded that the vapour from essential oil combinations can inhibit MRSA and may prove useful in eradicating the bacteria from wounds.
Long-term effects of lemon Despite the known effects of essential oils, there is still no definitive picture of the physiological changes that occur during olfactory stimulation, especially with regard to nociception and pain. Researchers had already shown that the acute exposure of rats to lemon essential oil produced sex differences in behavioural and neuronal responses. The same Italian group (Ceccarelli et al., 2004) examined the effects of long term lemon exposure on behavioural, hormonal and neuronal parameters. Eighty rats were divided into control and test groups of equal sexes. In the test group 150 ll of lemon essential oil was added to the animal’s cage every three days, for one week before the beginning of the tests and continuing throughout the tests and ending on day 12. The tests consisted of behaviours in the elevated plus-maze, thermal pain thresholds in a plantar test and spontaneous and nociceptive responses induced by a subcutaneous injection of a stimulus or a sham injection. Lastly, b-endorphin levels were measured in the hypothalamus and periaqueductal gray matter (PAG) areas of the brain. Blood samples were collected to determine corticosterone plasma levels. In both sexes, long-term exposure to lemon essential oil increased anxiety behaviour in the maze test and the thermal pain threshold was increased. The PAG b-endorphin content was lower in both sexes as compared to the control group.
Research reports One pathway to modify pain input is the descending aminergic pathway originating from the PAG and acting at the spinal cord level. It would appear that the essential oil affected this brain area, probably inducing a greater release of b-endorphin to modulate the nociceptive input. During prolonged nociception, sex-specific effects were noted in that females demonstrated antinociception whilst males did not. Hypothalamic b-endorphin was decreased in males but increased in females. As the hypothalamus is the site of b-endorphin synthesis, it was postulated that the essential oil-induced decrease of b-endorphin in males produced a lower reserve of endorphin that was less likely to affect prolonged nociception. Unlike the b-endorphin in the PAG, that of the hypothalamus is also involved in many other circuits, including those modulating arousal and attention. It was thought that the olfactory stimulation of the essential oil stimulated a female-specific circuit of the motor system. Corticosterone levels (that evaluate the degree of arousal of the hypothalamo-pituitary-adrenal axis) were greatly decreased by prolonged essential oil exposure in both injected and sham-injected animals. This was attributed to an adaptation of the corticosterone response, as caused by exposure to some types of stressors. In addition to the activated stress-like pathways able to produce an increase in the thermal pain threshold, the olfactory stimulation also ‘masked’ some of the negative aspects of inflammatory nociception, but only in females. It was concluded that activation of the olfactory-hippocampal pathway was sufficient to affect behaviour and nociception.
Antiviral melissa Infection with Herpes simplex virus (HSV) can be treated with antiviral drugs that interfere with virus-specific enzymes, e.g. fluorothymidine, but due to their cytotoxic effects, they are not widely used. A less cytotoxic drug, acyclovir, is the preferred treatment although it has been reported to be inefficient in treating genital herpes caused by HSV-2. In addition, HSV-2 has also been found to acquire resistance to these drugs. For these reasons, the search for new anti-HSV drugs is on the increase and those derived from plants are especially promising. A number of previous studies had demonstrated the antiviral properties of Melissa officinalis extracts on a number of viruses including HSV; the
155 activity was attributed to a non-tannin polyphenolic fraction, but the essential oil itself was not tested. A Turkish study (Allahverdiyev et al., 2004) has evaluated the in vitro antiviral activity of the essential oil against HSV-2. The experiment was carried out on human larynx epidermoid carcinoma cells (Hep-2 cell line) infected with HSV-2. The cytotoxicity of the essential oil was determined by adding various concentrations of the oil (25–200 ll/ml) to cell cultures and allowing them to grow for 48 h before examination. The highest noncytocidal concentration was found to be 100 ll/ml and so this concentration was used in the determination of antiviral activity. The essential oil was found to reduce the viral infectivity of three different infective doses of HSV-2. Acyclovir was used as the control. The virus titre was estimated from cytopathogenicity and expressed as 50% tissue culture infectious dose per millilitre (TCID50). At 1 and 10 TCID50, the antiviral effect of the essential oil was not statistically different from that of acyclovir, but at 100TCID50, the effect was lower than that of acyclovir. The inhibition of proliferation of HSV-2 by the essential oil varied inversely with the concentration of the virus. It was concluded that the essential oil of Turkish M. officinalis contained an anti-HSV-2 component.
Anticholinesterase terpenoids Enhancement of the cholinergic deficit associated with Alzheimer’s disease is currently based on the inhibition of the enzyme acetylcholinesterase (AChE). Previous research had shown that the essential oil of Salvia lavandulaefolia possessed in vitro and in vivo anticholinesterase activity. This activity was thought to be due to a synergistic activity within the oil rather than from a single inhibitor, and so a UK study (Savelev et al., 2003) examined the individual and combined activities of a number of components. Their work was based on the hypothesis that the activity of the essential oil was greater than the combined activity of individual components in their naturally occurring ratios. The components investigated were 1,8-cineole, camphor, a-pinene, b-pinene, borneol, caryophyllene oxide, linalol and bornyl acetate, ranging from 26.8% to 0.7% concentration in the essential oil, respectively. The components were initially divided into those that reached 50% inhibition of AChE and those that
156 were less potent. The IC50 value of the essential oil was not significantly different from that of 1,8-cineole, which itself was marginally less than the IC50 value of a-pinene. The other components had significantly less anticholinesterase activity. On the basis of their naturally occurring concentrations in the essential oil, the components were assessed in combinations for their anticholinesterase activity. As 1,8-cineole accounted for half of the activity of the essential oil, it was considered as the main agent that could show synergy with other components. A minor synergy was seen with 1,8-cineole/ a-pinene and 1,8-cineole/caryophyllene oxide combinations whereas a combination of 1,8-cineole and camphor was significantly antagonistic. In combinations of the remaining six components, synergism was or was not determined, according to the method of analysis employed. It was thus found that the inhibitory activity of the essential oil towards AChE resulted from a complex interaction between component terpenes involving both synergistic and antagonistic responses. Based on the findings, it was suggested
B. Harris that the essential oil of Salvia fruticosa may possess a higher anticholinesterase activity because it contained 1,8-cineole up to 75% and a relatively low camphor content.
References Allahverdiyev A, Duran N, Ozguven M, Koltas S. Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2. Phytomed 2004;11: 657–61. Ceccarelli I, Lariviere WR, Fiorenzani P, Sacerdote P, Aloisi AM. Effects of long-term exposure of lemon essential oil odor on behavioral, hormonal and neuronal parameters in male and female rats. Brain Res 2004;1001:78–86. Edwards-Jones V, Buck R, Shawcross SG, Dawson MM, Dunn K. The effect of essential oils on methicillin-resistant Staphylococcus aureus using a dressing model. Burns 2004;30:772–7. Savelev S, Okello E, Perry NSL, Wilkins RM, Perry EK. Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharmacol Biochem Behav 2003;75:661–8. Warnke PH, Ac ¸il Y, Springer IN, Sherry E, Reynolds M, Russo RAJ, et al. Tumor smell reduction with antibacterial essential oils. Cancer 2004;100:879–80.