Functional properties and toxicity

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Lavender has antimicrobial, pharmacological, physiological and miscellaneous functions. 11.5.1 Pharmacological effects

Plant (1920) applied 'waters of lavender' to the intestine of dogs in vivo and reported increased activity, which was sometimes followed by relaxation and decreased peristaltic activity. Linalool was reported to relax the small intestine of the mouse (Imaseki and Kitabatake, 1962) while Shipochliev (1968) observed a spasmolytic action on rabbit and guinea pig gut by the essential oil of lavender (L. spica L.). Reiter and Brandt (1985) report that linalool relaxes the longitudinal muscle of guinea pig ileum. A spasmolytic activity of L. dentata L. oil and its components 1,8-cineole and a- and P-pinene, has been observed on rat duodenum. Izzo et al. (1996) showed that the essential oil of L. angustifolia Mill. relaxed both longitudinal and circular muscle of the guinea pig ileum. There appears therefore to be good agreement that the oils of lavender are spasmolytic on intestinal muscle but Lis-Balchin et al. (1996a, 1996b) and Lis-Balchin and Hart (1999) reported that, with some commercial samples, the spasmolytic action is preceded by a contraction on guinea pig ileum.

Recent experiments using three different extracts of several Lavandula species, including a cold methanolic extract, a tea (made with boiling water) and a hydrosol (the water remaining after steam/water distillation) showed that the methanolic extracts of L. angustifolia dried flowers, L. angustifolia fresh flowers and fresh leaves, assessed separately, L. stoechas leaves and L. viridis leaves have a spasmolytic action on the guinea pig ileum. All the teas and hydrosols, except for L. angustifolia dried flowers and L. angustifolia fresh leaves, were also spasmolytic, while the water-soluble tea extract of L. angustifolia dried flowers and the leaves of L. angustifolia showed an initial spasmogenic action (Hart and Lis-Balchin, 2002). Brandt (1988) reported the spasmolytic actions of linalool on tracheal muscle.

Action on skeletal muscle of the essential oil of L. angustifolia Miller and also linalool and linalyl acetate produced a reduction in the size of the contraction in response to stimulation of the phrenic nerve and also when the muscle was stimulated directly (Lis-Balchin and Hart, 1997a). Thus the action would appear to be myogenic; however, Ghelardini et al. (1999) interpret their similar results as showing a local anaesthetic action; similarly, Re et al. (2000) conclude from experiments on mouse neuromuscular junction that linalool has a local anaesthetic action. Linalyl acetate also caused an increase in baseline or resting tone (Lis-Balchin and Hart, 1997a), while limonene caused a rise in tone, with a decrease in the size of the contractions.

Lavender oil, linalool, linalyl acetate, a and P-pinene and 1,8-cineole reduce uterine activity at concentrations that are spasmolytic on intestinal muscle (Lis-Balchin and Hart, 1997b).

Mode of action

All essential oils of different lavenders showed a post-synaptic effect on the guinea pig ileum and none possesses atropine-like activity (Lis-Balchin and Hart, 1999) or appears to stimulate adrenoceptors. Lavender oil and linalool, appear to mediate a spasmolytic action on intestinal smooth muscle via a rise in cAMP (Lis-Balchin and Hart, 1999). There is no evidence of the use of calcium channels except at very high concentrations. This is in contrast to other essential oils (Vuorela et al., 1997). There is no evidence for potassium channel opening. The essential oil from L. dentata L., and its component 1,8-cineole, has been shown to inhibit calcium-induced contraction of rat duodenum. There is recent evidence to show that the methanolic extracts of L. angustifolia (dry flowers, fresh flowers and fresh leaves) are calcium channel blockers, as are the leaves of L. viridis and L. stoechas (Hart and Lis-Balchin, 2002).

The fact that some extracts of L. angustifolia have a strong spasmogenic action (dried flowers and fresh leaves) is somewhat disturbing as so many modern herbal and aromatherapy books state that the teas are sedative and are often prescribed for upset stomachs. The results support the findings (Castle and Lis-Balchin, 2002; Lis-Balchin, 2002a,d) that the information on lavender has been mistakenly transcribed from early herbals, such as those of Culpeper (1653), where L. spica, a more camphoric lavender, was used medicinally and not the very floral L. angustifolia. The spasmolytic results shown for the water-soluble extracts of the more camphoraceous L. stoechas again supports the well-quoted action of the camphora-ceous spike lavender over the centuries and emphasizes the confusion.

11.5.2 Physiological effect

Evidence for the sedative properties of the EO of lavender after inhalation in animals is provided by Buchbauer et al. (1991, 1993) as it significantly decreased the motility of 'normal' test mice as well as that of animals rendered hyperactive or 'stressed' by an intraperitoneal caffeine. The main constituents of this oil, linalool and linalyl acetate, elicited a similar effect, which was dose related. The absorption of linalool from percutaneous application of lavender oil (Jager et al., 1992) provided some evidence for the aromatherapeutical use of lavender. Stress and travel sickness of pigs was reduced by lavender straw, measured by concentrations of cortisol in the pigs' saliva (Bradshaw et al.,

1998). Linalool, which has a dose-dependent, sedative effect on the central nervous system of rats (Elisabetsky et al., 1995a), may be caused by its inhibitory activity on glutamate binding in the cortex (Elisabetsky et al., 1995b). Potentiation of GABAA receptors expressed in Xenopus oocytes by perfumes and phytocides, including lavender oils and lavender perfumes, (shown by benzodiazepine, barbiturates, steroids and anaesthetics, which induce an anxiolytic, anticonvulsant and sedative effect) was investigated by Aoshima and Hamamoto (1999).

Swiss mice showed sedation after lavender oil (1/60 in olive oil) was orally administered (Guillemain et al., 1989). Lavender inhalation showed a similar effect (Komori et al., 1997). The positive effects of lavender oil as treatment for insomnia was indicated in a limited study of four elderly people (Hardy et al., 1995). A Japanese patent application for the usage of several monoterpenes (which can be incorporated into food such as chewing gums) as brain stimulants and/or enhancers of brain activity was filed by Nakamatsu (1995). Certain central neurotropic effects of lavender essential oil were shown by Atanassova-Shopova and Roussinov (1970). A more detailed account of physiological and other effects is given by Buchbauer (2002).

11.5.3 Psychological effects

Scientific research into the psychological (often referred to as psychopharmacological) effects of lavender is limited; however, there is a long history of it being regarded, and used, as a sedative or calming agent (Kirk-Smith, 2002). The effects on cells and brain tissues also suggest both reduction in electrical activity and an anti-convulsant effect. Both laboratory and clinically based studies reveal that responses to lavender may be determined not only by these pharmacological sedative effects, but by individual, situational and expectational factors independent of the lavender odour itself.

Many fragrances have been shown to have an effect on mood and, in general, pleasant odours generate happy memories, more positive feelings and a general sense of well-being (Warren and Warrenburg, 1993). Inhalation of lavender was found to have a sedative effect on people (judging by CNV studies) (Kubota et al., 1992; Torii et al., 1988; Manley, 1993). This was in agreement with the reduced motility in mice (Buchbauer, 1992; Jager et al., 1992; Kovar et al., 1987; Ammon, 1989).

Inhalation studies in people, of rosemary oil versus lavender oil using EEG and simple maths computations, showed that lavender increased a-power, suggesting drowsiness, while rosemary instigated decreased frontal alpha and beta power, suggesting increased alertness with faster and more accurate results in the maths (Diego et al., 1998). These results seem to show that odour has an effect on performance per se, but Knasko et al. (1990), who lied to their subjects that odour would be given, also showed an improvement in carrying out tasks, i.e. mind over matter! Karamat et al. (1992), however, found that lavender had a stimulant effect on decision times in human experiments. Subjects in a group given an ambient odour of dimethyl sulphide were less happy than those in the lavender group on both odour and non-odour days (Knasko, 1992). Ambient odours of lavender and cloves given to 72 volunteers (Ludvigson and Rottman, 1989) showed that lavender adversely influenced arithmetic reasoning. Lavender (at imperceptible levels) reduced the number of errors made in the arithmetical and concentration tasks compared to jasmine (Degel and Koster, 1999) and reduced stress in flight controllers (Leshchinskaia et al., 1983).

Most clinical studies initiated by aromatherapists used lavender oil, and showed little, if any, benefit (Vickers, 1996; Cooke and Ernst, 2000; Lis-Balchin, 2002d). There was no significant difference shown between the use of aromatherapy (with lavender), massage and periods of rest in an intensive care unit (Dunn et al., 1995). Aromatherapy massage on four patients with severe dementia and disturbed behaviour proved detrimental for most (Brooker et al., 1997).

The main action of essential oils is probably on the primitive, unconscious, limbic system of the brain (Lis-Balchin, 1997), which is not under the control of the cerebrum or higher centres and has a great subconscious effect on the person. Mood and behaviour could be influenced by odours, and memories of past odour associations could also be dominant, an area that needs to be fully explored before aromatherapy is used by psychologically unqualified persons in the treatment of Alzheimer's or other ageing diseases. Aromatherapy can, however, be effective in reducing stress and improving moods of terminally ill patients, but only in association with touch and the time to listen to the patient, as aromatherapy, like other alternative medicines, has a placebo effect owing to the greater time spent by the therapist with the patient, the belief imparted by the therapist and the willingness of the patient to believe in the therapy (Benson and Stark, 1996).

11.5.4 Antimicrobial effects

The antimicrobial activity of lavender oil against different bacterial species of lavender is moderate, in contrast to the considerable antimicrobial status awarded to lavender by aromatherapists (Deans, 2002). Lavender was found to be most effective against Enterococcus faecalis out of 25 bacteria, but Klebsiella pneumoniae enhanced growth! The genus Bacillus has been shown to be susceptible to lavender volatile oil by Jeanfils et al. (1991) and Lis-Balchin et al. (1998), the latter also showing differences in activity of different lavenders against 25 bacteria. Similarly, using 20 strains of Listeria monocytogenes, Lis-Balchin and Deans (1997) showed a wide variation in activity of different commercial lavenders. Vokou et al. (1993) suppressed potato sprout growth using crude herb material. Lavender also possesses antifungal properties, e.g. against Aspergillus niger, A. ochraceus and Fusarium culmorum, which all reacted differently to the oils (Lis-Balchin et al., 1998).

11.5.5 Other properties of lavender oil or its components

A study on mast cell-mediated immediate-type allergic reactions induced by an irritant in test animals showed a dose-dependent beneficial effect of lavender oil administered either topically or intradermally (Kim and Cho, 1999). Lavender flowers had a protective effect against enzyme-dependent lipid peroxidation (Hohmann et al., 1999). Lipid peroxidation and lipid metabolism studies in patients with chronic bronchitis showed normalization of the level of total lipids by lavender oil (Siurin, 1997). Inhalation of lavender oil had no effect on the content of cholesterol in the blood, but reduced its content in the aorta and atherosclerotic plaques (Nikolaevskii et al., 1990). Linalool showed only marginal effects on lipid peroxidation of polyunsaturated fatty acids (PUFAs) (Reddy and Lokesch, 1992). Yamada et al. (1994) showed anticonvulsive effects of inhaling lavender oil vapour and Elizabetsky et al. (1999) showed similar effects for linalool in glutamate-related seizure models.

A hypoglycaemic effect of various species of lavender was shown by Gamez et al. (1987a,b). Linalool leads to a hepatic peroxysomal and microsomal enzyme induction in rats (Roffey et al., 1990; Chadba and Madyasthe, 1984) and choleretic and cholagogic activity of Bulgarian lavender oil and a mixture of linalool and a-terpinol was found by Peana et al. (1994) and Gruncharov (1973). Some periodontal diseases can be treated with a mixture of

EOs, including lavender (Sysoev and Lanina, 1990). Lavender oil was said to be suitable for prevention and treatment of decubitus ulcers, insect bites, athletes' foot and skin rash and can also be used for the topical treatment of acne, prevention of facial scarring and blemishes of the face and body (Hartwig 1996). The EO of lavender was used in a mixture as a hair growth stimulant and for the treatment of Alopecia areata (Hay et al., 1998) and in a pilot study to determine possible novel, safe pediculicides in children. Skin penetration enhancers, especially for the transdermal absorption of various drugs and medicaments have included lavender oil with Nifedipine (Thacharodi and Rao, 1994). Research into cell cultures of L. vera for rosmarinic acid production was discussed by Ilieva-Stoilova et al. (2002).

There are numerous miscellaneous uses for lavender flowers, both fresh and dried (Lis-Balchin, 2002d) e.g. herbal pillows, lavender bags, household cleaning products and scented candles. Spike lavender is included in some veterinary shampoos and other products as an insect, especially flea repellent (Potter, 1988). Lavender oil is used as a component in topical formulations to relieve the pain associated with rheumatic and musculo-skeletal disorders, acting as a potent radical scavenger (Billany et al., 1995).

Perillyl alcohol, a minor component of lavender and the most important metabolite of D-limonene, is a chemo-preventative and chemo-therapeutic agent (Reddy et al., 1997; Bellanger, 1998), e.g. against rat liver cancer and rodent mammary and pancreatic tumours). Pancreatic tumours were inhibited completely by geraniol at 20 g/kg diet and 50% by perillyl alcohol at 40 g/kg diet in hamsters. Patents have been taken out for various uses of perillyl alcohol including: antibiotic and anti-fungal action (US Patent 5,110,832) and carcinoma regression (US Patent 5,414,019).

Contemporary patents for lavender include: wound treatment (US Patent 4,318,906); treating skin and scalp conditions (US Patent 4,855,131); minor skin irritations, promoting healing, resisting insects (US Patent 5,620,695); fly and mosquito attractant (US Patent 5,635,174) and control of dermatomycoses and dermatophytoses of skin ailments with Tinea pedis (US Patent 5,641,481).

11.5.6 Toxicity of lavender essential oils

Culpeper (1653) said that lavender (L. vera) 'provokes menses of women, and expels both a stillborn child and afterbirth' (the only reference to lavender as an abortifacient).

The BIBRA Working Group (1994) showed little or no irritation to human and animal skin, but it has caused sensitization, photosensitization and pigmentation. Patch tests have shown a few allergies due to photosensitization and also pigmentation (Brandao, 1986; Nakayama et al., 1976). Its principal effect following administration by oral, injection or inhalation routes to rodents was sedation. Linalool was irritant to the skin of various species of laboratory animals. There was the danger of causing dermatitis in sensitive people (Rudzki et al., 1976), e.g. an occupational allergy to a lavender shampoo used by a hairdresser (Brandao, 1986; Menard, 1961). Facial 'pillow' dermatitis due to lavender oil allergy was described by Coulson and Khan (1999). Facial psoriasis caused by contact allergy to linalool and hydroxycitronellal in an after-shave was described by De Groot and Liem (1983). Patch testing using lavender oil at 20% in petrolatum on patients suspected of suffering from cosmetic contact dermatitis over a nine-year period in Japan showed a dramatic increase in 1997, which coincided with the importation of the aromatherapy trend for using lavender oil and dried flowers. There is also the danger of airborne contact allergic dermatitis through overuse of essential oils and their storage (Schaller and Korting, 1995), which produced a severe response in a man who had been active with essential oils.

11.5.7 d-Limonene toxicity

Although present in small quantities in most lavenders, except L. stoechas, the dangers of D-limonene sensitization have become more prominent as it is used in so many industrial processes, e.g. degreasing metal before industrial painting, cleaning assemblies and as a hand cleanser. It oxidizes to R-(-) carvone, cis and trans-isomers of limonene oxide and hydroperoxides, all potential contact allergens (Karlberg et al., 1994). Two per cent of dermatitis patients gave a positive patch test to D-limonene (Karlberg and Dooms-Goossens, 1997), especially when aged (Chang et al., 1997). Pulmonary exposure of human volunteers to D-limonene caused a decrease in the lung vital capacity (Falk-Filipsson et al., 1993). The major volatile component of lactating mothers' milk in the USA contained D-limonene (von Burg, 1995), thus making it possible that the baby could develop an allergic response soon after birth. Cats and dogs, too, are very susceptible to insecticides and baths containing D-limonene.

In contrast to all the toxicity, anticarcinogenic properties of D-limonene were shown in vitro, when applied subcutaneously to mice that were then injected with benzopentaphene, but although the lung tumours took longer to develop and therefore the animals lived longer, it did not prevent them forming (Homburger et al., 1971).

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