Flower Power: An Overview on Chemistry and Biological Impact of Selected Essential Oils from Blossoms^{[ # ]}

Abstract

Natural raw materials such as essential oils have received more and more attention in recent decades, whether in the food industry, as flavorings and preservatives, or as insecticides and insect repellents. They are, furthermore, very popular as fragrances in perfumes, cosmetics, and household products. In addition, aromatherapy is widely used to complement conventional medicine. This review summarizes investigations on the chemical composition and the most important biological impacts of essential oils and volatile compounds extracted from selected aromatic blossoms, including Lavandula angustifolia, Matricaria recutita, Rosa x damascena, Jasminum grandiflorum, Citrus x aurantium, Cananga odorata, and Michelia alba. The literature was collected from PubMed, Google Scholar, and Science Direct. Blossom essential oils discussed in this work are used in a wide variety of clinical issues. The application is consistently described as safe in studies and meta-analyses, although there are notes that using essential oils can also have side effects, especially dermatologically. However, it can be considered as confirmed that essential oils have positive influences on humans and can improve quality of life in patients with psychiatric disorders, critically ill patients, and patients in other exceptional situations. Although the positive effect of essential oils from blossoms has repeatedly been reported, evidence-based clinical investigations are still underrepresented, and the need for research is demanded.

Key words

Aromatherapy - odor - volatiles - health care

Introduction

Essential oils are complex natural mixtures of volatile plant secondary metabolites with low molecular weight, isolated from various aromatic plants [1], [2]. They are liquid, clear, and colorless to yellow, apart from a few exceptions like blue chamomile oil. Furthermore, they are lipophilic and dissoluble in alcohol and organic solvents with a generally lower density than water [3]. All parts of the plant, such as blossoms, leaves, stems, fruits, seeds, barks, or roots, can produce essential oils by glandular trichomes or other secretory tissues and retain them in oil or resin cells, ducts, cavities, or glandular hairs and scales [3], [4]. The main components of essential oils from blossoms responsible for the fragrance, flavor, and biological activity belong to the group of terpenoids (mainly mono- and sesquiterpenes) and phenylpropanoids [2], [5].

Although many essential oils were considered to be simply metabolic waste products in the plant, it has been found that they have several important functions. Plants produce essential oils with antibacterial, antiviral, or antifungal compounds to prevent diseases caused by microorganisms [3]. Essential oils in blossoms are often applied as chemical weapons against herbivores or insects but also to attract other insects, birds, or bats to pollinate the plant, ensuring the persistence of the species [3], [6]. It has also been shown that some plants use their essential oils to communicate with nearby plants and warn them of predators [4]. Furthermore, essential oils may be synthesized to inhibit the sprouting and growth of other plants, thus minimizing competitors [7], [8]. The quality, quantity, and chemical composition of the essential oil vary widely, mainly depending on environmental factors, such as season, climate, soil quality and preparation, insect stress, and microorganisms, as well as the age and the part of the plant [5], [9]. Moreover, the time of harvesting can play a notable role in the quality and composition of an essential oil [10]. Therefore, extracting essential oils under almost identical circumstances is important to obtain a consistent composition [3]. Compared to other plant organs, blossoms usually provide lower oil yields [11].

There are various methods for the industrial production of essential oils, including conventional and innovative processes. Water and steam distillation, organic solvent extraction, and cold pressing are classical methods. Some innovative techniques are supercritical fluid extraction and ultrasound- or microwave-assisted extraction [12]. Extraction of essential oils by water or steam distillation is the most common and simplest way [13], and in addition to dry distillation and cold pressing, it is the only method described in the European Pharmacopoeia (10th edition, 2020, p. 9565). However, the odor quality can be negatively affected by the formation of artifacts or loss of volatile compounds due to heat exposure, which is why flower oils in particular are rarely steam-distilled [13]. The purposes of the more recent methods are to reduce extraction time and energy consumption and improve the essential oil yield and quality [12].

Essential oils were already used by the ancient Egyptians for healing purposes and play an important role in the ancient Indian healing art of Ayurveda. Hippocrates of Kos, who is considered the father of medicine, studied the effects of essential oils between the 5th and 4th century BC and recommended massages and fragrant baths for treating diseases. During the Renaissance in Europe, herbs and essential oils were brought to Europe from the Middle and Far East, and they were regarded as luxury goods at the time. French chemist René-Maurice Gattefossé studied the effects of lavender, thyme, lemon, and clove oils on wounded soldiers during World War I after accidentally discovering that his burned hand healed faster in lavender essential oil and left no scars. He was the first to use the term “aromatherapy” [14]. Today, essential oils are used in aromatherapy to treat diseases and disorders through inhalation and oral application, or externally as bath and massage additives [15], [16], [17]. Aromatherapy acts mainly through the psychological effect of smell via the olfactory system [18]. The application is consistently described as safe, which is why the application is also being investigated in vulnerable patients [19]. However, the literature also points out the risk of contact dermatitis that might appear from excessive or wrongly applied essential oil use [20], [21].

This review aims to highlight the importance of essential oils from blossoms in the fragrance, food, agricultural, and pharmaceutical industries. Seven essential oils from flowers were selected due to their high impact in cosmetics and aromatherapy, focusing on the major biological activities and their chemical composition. The chemical structures of the main constituents are listed in [Fig. 1]. The literature was collected from PubMed, Google Scholar, and ScienceDirect. The search was limited to publications between 1953 and 2023.

Fig. 1 Chemical structures of principal constituents of selected aromatic blossoms.

However, due to the high impact of bioactivities and only few available clinical studies, essential oils from blossoms and their components still need to be further investigated in evidence-based clinical trials to support their use as complementary natural remedies.

Essential Oils from Selected Blossoms

Lavender oil

Lavender essential oil is probably the most popular essential oil used in aromatherapy. It is mainly extracted from Lavandula angustifolia, also called true lavender, which is an evergreen flowering aromatic plant belonging to the Lamiaceae family [22]. The name derives from the Latin word “lavare” (“to wash”) and has a historical background, as the Romans added lavender flowers to their bath water, possibly for its fragrance and antimicrobial effect [23], [24]. “Angustifolia” is also Latin and indicates the plantʼs narrow leaves [25]. As early as the 1st century AD, Greek physician Pedanios Dioscorides reported on the biological effectiveness of lavender in his work De Materia Medica [23], [26]. In the Middle Ages, it was an important aromatic plant for perfume and soap production [23]. Nowadays, lavender oil is applied in aromatherapy by inhalation, peroral ingestion through capsules, and massage and as a bath additive [27].

L. angustifolia originated in the Mediterranean region but is now cultivated around the world [23], [28], [29]. Its essential oil is produced mainly in Bulgaria (52%), France (26%), China (12%), the United Kingdom, Ukraine, Spain, and Morocco [30], [31]; 300 to 500 tons are estimated to be produced worldwide per year, with yields varying from year to year due to differences in climatic conditions [31], [32].

More than 30 species belong to the genus Lavandula, which differ in morphological characteristics, growth height, chemical composition, and fragrance [24], [33]. Different species can be distinguished by the size and color of the bracts and the appearance of the two-lobed calyx and corolla [24]. The essential oil is mainly found in oil glands and hairs on the surface of the calyx [23]. It is colorless or pale yellow and has a strong floral, moderately spicy, camphor-like, woody, clove-like, herbal, and hay-like odor [23], [34]. In aromatherapy, it blends well with bergamot and other citrus oils, clove, patchouli, and rosemary [35]. In addition to true lavender, spike lavender or Spanish lavender (L. latifolia) and lavandin (Lavandula × intermedia), a sterile hybrid of L. angustifolia × L. latifolia, are used to produce essential oils [30]. Essential oils from different cultivars of the same lavender species may show different biological activities depending on their chemical composition, which in turn depends on growing conditions and processing after harvest [29]. The odor of the oil may vary depending on the cultivar. While true lavender oil is delicately fragrant, spike lavender oil is less fragrant due to its strong camphor aroma and is often used in cheaper lavender products [30]. The yield of L. angustifolia oil is relatively low compared to the other species, whereas the yield of lavandin oil can be up to 100 kg/ha, which is 85 kg/ha more than the yield of lavender oil, making lavandin oil attractive to the industry. Furthermore, it is cheaper [30], [36].

For simplicity and economy, the essential oil is usually obtained by steam distillation of lavender inflorescences [28], [37]. A higher yield is derived from fresh compared to dried flowers. This way, a higher yield of the main components and, thus, better antimicrobial and antioxidant activity, as well as better sensory properties, are obtained [29]. In addition, less plant material is required because a significant amount of essential oil is lost through drying (over 40%) [33]. Depending on climatic conditions, 1 kg of lavender oil is obtained from about 120 – 150 kg of lavender blossoms by steam distillation [37].

A search engine query on clinicaltrials.gov resulted in 61 ongoing studies, which clearly underlines its relevance (accessed on 11 August 2023 at 18 : 00, searching “lavender” in the headline). Furthermore, a search engine query on pubmed.ncbi.nlm.nih.gov (accessed on 11 August 2023 at 18 : 20) resulted in over 1000 studies in the past five years. The following will provide a rough overview on the relevant research findings and medical applications of lavender essential oil.

Chemical composition

L. angustifolia flowers are harvested from June to August in Europe and contain 2 to 3% essential oil consisting of about 100 compounds [30], [38]. They include mainly terpenes, which are mostly important for pharmacological effects [38]. Terpenes include monoterpenes (limonene ([Fig. 1 a]), myrcene, α-/β-pinene ([Fig. 1 b]), camphene, β-ocimene, 3-carene, and α-/γ-terpinene), monoterpene alcohols (linalool ([Fig. 1 c]), terpinen-4-ol, α-terpineol ([Fig. 1 d]), lavandulol, borneol, and 1-octen-3-ol), monoterpene esters (linalyl acetate ([Fig. 1 e]), lavandulol acetate, and geranyl acetate), monoterpene ketones (3-octanones and camphor ([Fig. 1 f])), monoterpene oxides (1,8-cineole ([Fig. 1 g])), and sesquiterpenes (β-caryophyllene ([Fig. 1 h]) and β-farnesene) ([Table 1]). The two major components are linalool and linalyl acetate, although the chemical composition varies widely depending on the above-mentioned factors, as well as the analysis method used to identify the constituents [30], [33], [39], [40]. According to the European Pharmacopoeia (10th edition, 2020, p. 2276 – 2277), only the use of inflorescences of L. angustifolia and the method of steam distillation for the extraction of lavender oil are valid. [Table 1] shows the value limits specified by the European Pharmacopoeia for the content of the most prominent compounds. In addition, data from the different literature on L. angustifolia essential oil grown in six different countries were added to show the great variety in the percentages of the compounds. These essential oils were derived by water distillation [29], [34], [41], [42] or steam distillation [40], [43] from dried [29], [34], [40], [42], [43] or fresh [41] blossoms. The constituents were determined by GC-MS.

Table 1 Chemical composition of essential oils of L. angustifolia blossoms from different countries [29], [34], [40], [41], [42] in comparison with the European Pharmacopoeia standards (10th edition, 2020, p. 2277).

Components	Italy (%) [43]	Poland (%) [29]	China (%) [34]	India (%) [41]	Morocco (%) [40]	Australia (%) [42]	PhEur limit values (%)
Values are given as relative percentages of compounds. Constituents were determined by GC-MS. PhEur = European Pharmacopoeia.
Linalool	28.36	34.70	29.01 ± 0.33	28.06	14.93	52.59 ± 0.70	20.00 – 45.00
Linalyl acetate	33.35	19.70	27.33 ± 5.05	47.56	11.17	9.27 ± 0.21	25.00 – 47.00
Terpinen-4-ol	5.50	2.00	2.24 ± 1.05	0.56	8.31	2.45 ± 0.02	0.10 – 8.00
1,8-Cineole	1.54	0.50	1.02 ± 0.27	1.14		0.51 ± 0.10	≤ 2.50
Limonene	1.53	0.60	0.95 ± 0.18	0.55	1.75	0.24 ± 0.01	≤ 1.00
Lavandulol acetate	1.28	4.50	1.72 ± 0.71	0.25			≥ 0.20
3-Octanone	0.27	1.40	0.28 ± 0.18				0.10 – 5.00
Camphor	0.25	0.30	0.38 ± 0.03	0.11		8.79 ± 0.20	≤ 1.20
α-Terpineol	0.31	5.10	2.03 ± 0.22	3.75		3.03 ± 0.17	≤ 2.00
Lavandulol	0.14	0.80	1.72 ± 0.71	0.25	1.59		≥ 0.10
Myrcene	3.56	1.50		0.55	0.90	0.56 ± 0.12
α-Pinene	0.29	0.20	0.28 ± 0.04	0.09	0.90
β-Pinene	0.14	0.40	0.70 ± 0.05
Camphene	0.10	0.30	0.33 ± 0.09	0.23	0.63	0.19 ± 0.00
Borneol	0.77	1.5		0.85	7.06	7.50 ± 0.12
β-Caryophyllene	5.75	1.00	3.67 ± 0.26	0.93	3.71	1.00 ± 0.13
Bergamotene	0.27	0.10	0.22 ± 0.05		0.54	0.07 ± 0.01
(Z)-β-Ocimene	5.44	2.90*	1.71 ± 0.37		0.36	0.44 ± 0.04
(E)-β-Ocimene	3.13	2.90*	4.38 ± 0.91	0.08		0.09 ± 0.00
3-Carene	0.15		0.78 ± 0.06		0.69
α-Terpinene	0.07					0.32 ± 0.02
γ-Terpinene	0.19		0.09 ± 0.04
1-Octen-3-ol	0.61	0.30	0.47 ± 0.08	0.53		0.28 ± 0.03
Geranyl acetate	0.78	2.30	1.23 ± 0.15	1.94	1.55
β-Farnesene	0.28	0.20	1.66 ± 0.38		2.49	1.83 ± 0.23

The major chemical compounds in all these oils were monoterpene alcohol linalool and monoterpene ester linalyl acetate. In the examples given, the content varied greatly between countries. While the two main constituents accounted for 75.62% in India, the sum of the values of the lavender oil from Morocco was about a third (26.1%). It is noticeable that the essential oil from India, which was obtained from fresh blossoms, had by far the highest content of linalool and linalyl acetate. Again, this proves the advantage of using fresh flowers over dried ones [29]. However, only the essential oils from Italy and China met the specifications of the European Pharmacopoeia. The linalyl acetate content of the Polish lavender oil was too low (19.70%), whereas the α-terpineol content was too high (5.10%). The concentration of linalool (34.70%) was in accordance with the European Pharmacopoeia, higher than from the Chinese (29.01%) or Italian (28.36%) oil. Furthermore, it had the highest lavandulol acetate amount (4.50%), which was much above the allowed concentration of 0.20%. In the Indian essential oil, the α-terpineol content was slightly too high (3.75%). The oil from Morocco did not comply with the European Pharmacopoeia at all. In contrast, the linalool concentration of the Australian oil was much higher (52.60%), but the linalyl acetate content was too low (9.27%). The amount of camphor even exceeded the maximum value by a factor of 8. The α-terpineol content was 3.03% and, thus, exceeded the limit of ≤ 2.00%. The amount of borneol was about seven times higher in the Moroccan and Australian oils than in the others [29], [34], [40], [41], [42], [43].

High content of linalool and linalyl acetate indicates a high quality of lavender essential oil [40]. Linalool, an acyclic tertiary monoterpene alcohol, is found not only in lavender but also in cinnamon, spearmint, sage, coriander, and nutmeg. It is barely soluble in water and very volatile and can be obtained synthetically. Two enantiomers of linalool exist, (3S)-(+)-linalool, which is also called coriandrol, and (3R)-(−)-linalool or licareol. Both exhibit different odors: licareol smells like lavender and is rather woody and is mainly contained in L. angustifolia and L. latifolia flowers. The scent of coriandrol is described as more floral, sweet, and citric, and the compound can be found in Coriandrum sativum fruits [44], [45]. Linalool can also occur as a racemic, for example, in passion fruits and apricots [44].

In comparison to L. angustifolia, L. latifolia contains about 70% of the three main components, 1,8-cineole (6.6 – 57.1%), linalool (3.7 – 61.1%), and camphor (1.1 – 46.7%). The quality of the oil is determined by the relative concentrations of these compounds. Linalyl acetate is present only in less than 1%. Annual climatic conditions and different altitudes in Spain showed an influence on the amount of essential oil produced, as well as its chemical composition [36]. For perfume and cosmetics production, high linalool and low camphor contents are desired [15]. If spike oil contains more camphor and 1,8-cineole, it is well suited for massages and inhalations in aromatherapy due to their anti-inflammatory, analgesic, antiviral, antispasmodic, mucolytic, and decongestant effects [15], [46]. Therefore, medicinal specialties containing L. latifolia (Tavipec) are thought to improve acute bronchitis symptoms, as well as to support antibiotic treatment during acute rhinosinusitis. Remedies containing L. angustifolia oil (Lasea) are mainly used for their sedative and anxiolytic effects [47], [48].

Investigations on biological activity

Antimicrobial activity

Numerous studies have reported the antiseptic activity of L. angustifolia flower essential oil [29], [38], [44], [49], [50], [51], [52], [53]. It is effective against Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, Listeria monocytogenes, and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Klebsiella pneumoniae, and Vibrio fluvialis), as well as yeasts and filamentous fungi (Candida albicans, Aspergillus niger, and Penicillium expansum), with the essential oil being much more effective against yeasts than against bacteria [29], [38], [44], [53]. Since the chemical composition of L. angustifolia essential oils varies according to the place of harvest, the antimicrobial activity also varies [29]. This can be explained by the fact that plants often secrete essential oils as a protection against corresponding environmental influences and as a defense against microbes and predators [51].

It was reported that monoterpenes without functional groups, such as limonene, were the least antibacterial active due to their low solubility in water and, thus, their low diffusion through the medium. Substances containing oxygen, especially alcoholic and phenolic groups, like linalool, showed higher antimicrobial activity [50]. It is important to mention that the essential oil is effective due to the synergistic effects of the components and not only due to the main components. The substances present in low concentrations can also be active [38], [50].

Linalool devitalizes bacterial cells by damaging the integrity of the bacterial cell membrane by reducing the membrane potential. This results in the leakage of cytoplasmic contents such as alkaline phosphatase, DNA, RNA, and proteins. Furthermore, linalool affects metabolites and key enzymes of diverse metabolic pathways such as glycolysis, citrate cycle, CoA biosynthesis, amino acid metabolism, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism [54], [55]. Linalool was effective against multi-resistant bacteria such as E. coli (MIC: 6 µL/mL) and P. aeruginosa (MIC: 7 µL/mL), which can cause life-threatening diseases [44].

As lavender as a food meets the GRAS (“generally recognized as safe”) criteria of the US Food and Drug Administration [19], lavender essential oil or linalool, which has been detected in 23 foods [44] such as Earl Grey black tea [56], are used as a preservative in food, for example, by spraying it into the headspace of packaging or applying it to coatings [44], [50], [57]. By incorporating linalool in nanoemulsions, stability could be increased, the odor problem could be solved, and reactions with food ingredients could be reduced [54], [57]. It is also used for vitamin E synthesis in the pharmaceutical industry [58].

According to antimicrobial properties, linalool also exhibits antifungal activities against yeast-like fungi (C. albicans) and dermatophytes (Trichophyton rubrum). A study reported the potential use of linalool against fluconazole-resistant T. rubrum strains in dermatophytoses. Linalool disrupted mycelial growth, conidiogenesis, conidia germination, and fungal morphogenesis [59]. Another study demonstrated that lavender essential oil had fungistatic and fungicidal effects against C. albicans strains, which cause the majority of local and systemic mycoses in humans. A distinctive feature is that C. albicans can reversibly switch between yeast and hyphal forms, known as dimorphism. Germ tube formation initiates the switch to the more phagocytosis-resistant hyphal form, creating an intense pressure that allows tissue penetration [52]. Lavender oil seems to inhibit germ tube formation by inducing stress through reactive oxygen species (ROS) generation and, thus, reduces the spreading of the fungus in the host tissues [52], [53]. Furthermore, linalool has been reported to inhibit the expression of HMG-CoA reductase in fungi, thus preventing ergosterol biosynthesis, leading to fungal cell death [53].

Anti-inflammatory activity

Another property of lavender essential oil is its anti-inflammatory activity [49], [51], [60], [61], [62]. It is believed that not one single compound was responsible for the anti-inflammatory effect, but it was the totality of the efficacy-determining substances, linalool, camphor, terpinen-4-ol, ocimene, and linalyl acetate [49], [51].

Gram-negative bacteria contain lipopolysaccharides (LPS) in their cell walls, which are recognized by the toll-like receptor 4 (TLR4) on monocytes and macrophages. As a response, they release cytokines (TNF-α, IL-1β), NO, and free radicals such as superoxide anions after activation of the NF-kB pathway, and inflammation results as a protective reaction of the body [49], [60], [63]. In an in vitro study, lavender oil downregulated the LPS-dependent release of superoxide anions and IL-1β, presumably by inhibiting NF-kB activation. This may attenuate the LPS-induced inflammatory response. Furthermore, the expression of TLR4 was also shown to be inhibited in LPS-stimulated cells. A cytoprotective effect has also been demonstrated, as lavender oil induced the expression of heat shock proteins [49].

Another study proved that lavender essential oil activated the human innate macrophage response to the bacterium S. aureus in vitro, increasing the phagocyte-scavenging activity and reducing intracellular bacterial proliferation. This could reduce severe, life-threatening complications caused by this pathogen. Stimulation of TLR-2 was found, as well as upregulation of heme oxygenase-1 (HO-1) expression, which inhibits inducible NO synthase and, thus, NO overproduction. Furthermore, the study demonstrated stimulation of the NADPH oxidase system, where NADPH is a direct antioxidant and scavenges free radicals. In addition, the essential oil suppressed S. aureus-induced cytokine production, and the corresponding receptors were downregulated, thereby uncontrolled inflammation, and tissue damage could be reduced [51]. LPS can also activate TLRs on immune cells in the central nervous system (CNS) called microglia, which protect the brain from pathogens [60]. Activation and overexpression of those TLRs on microglial cells and neurons play essential roles in the development of neurodegenerative diseases like Alzheimerʼs disease [60], [64]. TLRs activated the NF-kB pathway, leading to the expression of pro-inflammatory factors such as TNF-α, IL-1β, PGE₂, and NO, and thus, chronic inflammation ensued [60], [63]. One study demonstrated that linalool treatment had an anti-inflammatory effect on CNS microglial cells by inhibiting LPS-induced NF-kB activation and cytokine production. The underlying mechanism was determined as an increased expression of the Nrf2 transcription factor, which regulates inflammatory and antioxidant responses, and the antioxidant protein HO-1 [60]. Alzheimerʼs patients also suffer from decreased cholinergic excitatory transmission in the CNS and glutamate-induced neurotoxicity [65], [66]. Suppression of NF-kB activation by lavender essential oil inhibited TNF-α-induced cell adhesion molecules on vascular endothelial cells, reducing leukocyte migration into tissues and, thus, reducing inflammation [61].

Psychological effects

Lavender essential oil was further examined in the context of psychiatric disorders, such as anxiety, depression, stress, and sleep disorders [67]. The oil was thereby studied as a single therapeutic agent and together with other therapies (such as music therapy [68]) or in combination with other specialty medicines (such as lemon balm oil [69]). In addition, lavender was investigated in vulnerable patient cohorts like children [68], older people with dementia [69], or patients treated with chemotherapy [70]. The European Medicines Agency approves lavender essential oil as an herbal medicine to relieve mild symptoms of mental stress and fatigue and for sleep support, based on long-standing traditional use (EMA/HMPC/530 968/2012). Previous studies have demonstrated the sedative effect of lavender essential oil after inhalation. Motor activity was reduced in mice after inhalation exposure. This occurred at a much lower concentration than oral application [71].

True lavender oil was effective for sleep disorders in the elderly and in pregnant, postpartum, menopausal, and postmenopausal women, as well as patients with depression [19]. Inhalation of three drops of lavender oil every evening reduced anxiety and improved sleep quality in chemo patients [70]. Nightly lavender scent also improved studentsʼ sleep quality and reduced fatigue the following day [72]. In dementia patients, symptoms such as restlessness, aggressiveness, excitability, and sleeping disorders could be significantly improved by aromatherapy with lavender essential oil. This could play an important role for dementia patients suffering from side effects of psychotropic drugs [73]. Studies found that the effects of lavender inhalation therapy significantly reduced sleep problems, as well as stress emotions, anxiety, and depression, due to interaction with transient receptor potential channels (TRP), gamma-aminobutyric acid (GABA), serotonin receptors (5-HT), and dopamine receptors (DA) [74], [75]. Lavender essential oil is thought to act through the limbic system, where it may enhance the action of GABA in the amygdala [18]. However, while some studies have reported the modulatory effect of linalool on GABAergic neurotransmission [29], [76], [77], other studies have failed to demonstrate this effect [78], [79]. Furthermore, a dose-dependent antagonism at the NMDA (N-methyl-D-aspartate) receptor was reported, for which mainly linalyl acetate – but also linalool – were believed to be responsible, exerting the oils nerve-calming, anxiolytic, and neuroprotective effects. In addition, linalool in lavender oil binds to the serotonin transporter (SERT) due to the free hydroxyl group, which explains the antidepressant effect [78]. There are further promising results regarding the anxiolytic and antidepressant effects of using lavender essential oil in different application forms [67], [80]. However, other investigations on the effect of lavender oil on perioperative pain, anxiety, sleep, and depression did not observe any significant effect: a meta-analysis that examined 65 randomized clinical trials on the effects of lavender on anxiety criticized the low to average quality of the available studies [81].

Other activity

Several studies focused on lavender as a valuable therapeutic agent in severe somatic illnesses. Treatment with lavender aromatherapy positively affected pain in patients after coronary bypass graft surgery and decreased the need for pain relievers [82]. The analgesic effect of linalool has long been known, but the mechanism of action is not yet fully understood. Competitive inhibition of N-methyl-D-aspartate (NMDA) receptors has been demonstrated, resulting in an antinociceptive effect. Linalool could also be analgesic through cholinesterase inhibitory action due to the involvement of muscarinic neurotransmission in antinociception in the rat spinal cord. Inhibition of cyclooxygenase has also been considered [83]. Lavender essential oil has also been observed to have a local anesthetic effect [84]. A smaller, single-blinded, randomized controlled trial investigated the use of lavender oil in patients with ostomy bags. It concluded that lavender essential oil was a simple and natural method to eliminate odor and increase quality of life [85].

Chamomile oil

Another important essential oil in aromatherapy is chamomile oil, extracted from the medicinal, aromatic plant Matricaria recutita. The use of chamomile flower essential oil is widespread in the pharmaceutical, cosmetic, perfumery and food industries [86], [87]. The European Pharmacopoeia (10th edition, 2020, p. 2252 – 2253) describes chamomile oil (Matricariae aetheroleum) as an intense blue essential oil with a characteristic odor obtained from fresh or dried flower heads or flowering shoot tips of M. recutita by steam distillation. The name “chamomile” derives from two Greek words, “chamos” (ground) and “melos” (apple), referring to the fact that the plant is low-growing and to its apple-like scented fresh flowers [88], [89], [90]. It was already used in ancient times, when famous doctors such as Hippocrates and Galen reported about it [91].

M. recutita or M. chamomilla (German chamomile) is an annual herbaceous plant of the Asteraceae family with a sweet, slightly fruity, and grass-like flavor [86], [91]. M. recutita is native to Europe and West Asia and cultivated around the world [92]. The plant can be found in tropical and cold climatic conditions due to adaptation, as well as different soil conditions [92], [93]. Seeds need open ground to persist, so it often grows as a weed near roadways, landfills, and farmed fields [88]. In China, flowers can be harvested from May to July [92], whereas the main harvest period in northern India is reported to be between March and April [86]. Harvest time plays an important role in the composition of chamomile essential oil. The highest essential oil content is said to be obtained when the blossoms are harvested between 10 : 00 and noon. In the evening, between 18 : 00 and 20 : 00, the flowers contain the lowest amount of essential oil [94]. The highest oil content can be derived from flowers just before full bloom [86].

The use of Chamaemelum nobile (Roman chamomile) is also common in traditional herbal medicine, although German chamomile is usually used and prescribed in the European Pharmacopoeia [91]. While the essential oil extracted from German chamomile is deep blue, the Roman chamomile provides a light blue essential oil due to the much lower chamazulene ([Fig. 1 i]) content [88]. The terpenoid content of the Roman species is generally lower [95].

A search engine query on clinicaltrial.gov resulted in 24 ongoing studies (accessed on 20 August 2023, 13 : 00). A query on pubmed.ncbi.nlm.nih.gov showed 64 clinical trials in the past 10 years (accessed on 20 August 2023, 13 : 15). A combined query with “Chamomile AND essential oil” resulted in six outcomes (pubmed.ncbi.nlm.nih.gov, accessed 20 August 2023, 15 : 00). The effect of chamomile extract is examined in many studies [96], [97]. Chamomile oil has interesting application areas, although these are significantly fewer results than in lavender oil.

Chemical composition

Blossoms retain 0.24 – 2.0% essential oil with the main terpenoids α-bisabolol ([Fig. 1 j]) and its oxides A and B, bisabolone oxide A, chamazulene, and β-farnesene [91], [98]. Furthermore, linalool, α-terpineol, terpinene-4-ol, 1,8-cineole, limonene, α-pinene, β-caryophyllene, borneol, p-cymene, and some others could be detected in tiny amounts [99]. In total, chamomile essential oil contains more than 120 components [88].

As with lavender, the chemical composition of chamomile essential oil depends on the plant species, genetic factors, and geographical region, as well as the drying and extraction method [87], [100], [101], [102]. [Table 2] shows the most important chemical compounds of German chamomile essential oil from several European countries, India, Iran, Egypt, and Bosnia and Herzegovina [87], [99], [103], [104], [105], as well as the European Pharmacopoeia (10th edition, 2020, p. 2254) value limits. The European Pharmacopoeia distinguishes between two chamomile oils, one rich in bisabolol oxides (oil A) and the other rich in α-bisabolol (oil B). However, the European Pharmacopoeia does not differentiate between bisabolol oxide A and B. The total content of bisabolol oxides and α-bisabolol should be at least 20% in oil A, but no limits are prescribed for oil B. Some European [87] and Egyptian [104] oils were in accordance with the European Pharmacopoeia and were rich in bisabolol oxides and α-bisabolol, as well as the Indian oil [99]. The chamomile oils from Bosnia and Herzegovina [105] and from Iran [103] did not comply, as they did not meet the regulations for oil A or oil B. The main components of chamomile oil are α-bisabolol and chamazulene, which account for up to 60% of the total content in European oils but may be much less ([Table 2]). The composition and yield differ depending on the blossomsʼ source and age [91].

Table 2 Chemical composition of essential oils of M. recutita blossoms from different countries [87], [99], [103], [104], [105] in comparison with the European Pharmacopoeia (10th edition, 2020, p. 2254).

Components	Europe (%) [87]	India (%) [99]	Iran (%) [103]	Egypt (%) [104]	Bosnia and Herzegovina (%) [105]	PhEur Limits (%) A	PhEur Limits (%) B
Values are given as relative percentages of compounds. The constituents were determined by GC-MS. PhEur = European Pharmacopoeia. PhEur distinguishes two chamomile oils, one rich in bisabolol oxides (oil A) and the other rich in (−)-α-bisabolol (oil B). The total content of bisabolol oxides and (−)-α-bisabolol in oil A should be at least 20%; for oil B, no values are prescribed. * PhEur does not differentiate between bisabolol oxide A and B.
Chamazulene	0.7 – 15.3	5.6	4.2	0.45 – 1.54	6.4	≥ 1.0	≥ 1.0
α-Bisabolol	0.1 – 44.2	16.0	5.0	7.66 – 16.42	2.4		10 – 65
α-Bisabolol oxide A	3.1 – 56.0	36.5	21.5	11.61 – 16.57	7.0	29 – 81*
α-Bisabolol oxide B	3.9 – 27.2	8.6	7.0	25.31 – 32.99	6.3
α-Bisabolone oxide A	0.5 – 24.8	0.4	10.0		3.0
β-Bisabolone	0.0 – 0.4		0.2
β-Farnesene	2.3 – 6.6	14.0	6.1	1.54 – 21.85	29.8
α-Farnesene	0.0 – 1.3	0.6			9.3
(Z)-Spiroether (cis-en-yn-dicycloether)	8.8 – 26.1	2.8		5.82 – 8.57	5.1
Spathulenol	1.7 – 4.8	0.1	9.4	0.8 – 3.67	0.2
Germacrene D	0.1 – 1.7	1.6	0.8		6.2
α-Pinene	0.1	0.1	0.1		1.9
Limonene	0.1 – 0.4	0.3	0.2		0.3
1,8-Cineol	0.1 – 0.5	0.1	2.1		0.1
Linalool	0.1 – 0.3	0.1	0.1		0.3

The monocyclic sesquiterpene alcohol α-bisabolol is liquid, clear, and colorless with a fruity, coconut-like aroma. It is insoluble in water and slightly soluble in ethanol [106]. The oil quality can be assessed by the deep blue color caused by chamazulene due to the conjugated system [107], which does not appear naturally in chamomile oil but is formed from the sesquiterpene lactone matricine during steam distillation [87], [107]. When chamomile flowers are heated to about 100 °C, acetic acid and water are removed from matricine to form chamazulene carboxylic acid. Chamazulene is formed from this after carbon dioxide is removed ([Fig. 2]).

Fig. 2 Transformation from colorless matricine to blue chamazulene during steam distillation.

Investigations on biological activity

Anti-inflammatory and immunoregulatory activity

Various in vitro and in vivo studies have demonstrated that α-bisabolol had antimicrobial, anti-inflammatory, anti-irritant, analgesic, and anticancer activity, as well as neuro-, cardio-, and nephroprotective effects [106], [108]. For example, α-bisabolol inhibited nephrotoxicity upon doxorubicin administration, an antineoplastic agent from the anthracycline group, by neutralizing doxorubicin-induced free radicals, as well as by interfering with NF-κB/MAPK signaling cascades and inhibiting caspase-dependent apoptosis [108]. In in vitro, in vivo, and in silico studies, α-(−)-bisabolol inhibited pro-inflammatory cytokine production, alleviated skin inflammation, and showed the strongest antiphlogistic activity among all constituents [109], [110]. It was also demonstrated in vitro that matricine inhibited LPS- and TNF-α-induced gene expression of the adhesion molecule ICAM-1 in a concentration-dependent manner (10 – 75 µM) by inhibiting NF-kB signaling in endothelial cells, thereby exerting an anti-inflammatory effect. Chamazulene was inactive [111]. Chamazulene was further found to exhibit anti-inflammatory activity by inhibiting the formation of leukotriene B₄ from arachidonic acid in neutrophil granulocytes [107]. The effects of proazulene matricine, as well as the azulenes chamazulene and guaiazulene, proved to be very different. A study reported that matricine had the most potent antiphlogistic effect, being about as effective as α-bisabolol. Chamazulene and guaiazulene were about equally effective, although the duration of action of chamazulene was significantly longer [112]. The degradation product, chamazulene carboxylic acid, inhibited cyclooxygenase-2 (but not cyclooxygenase-1) and had anti-inflammatory effects in several animal models with local and systemic applications [113]. Spiroethers ([Fig. 1 k]) are also known for their anti-inflammatory and antispasmodic properties, but they are easily decomposed at elevated temperatures [93].

Furthermore, an immunoregulatory potential of chamomile oil could be demonstrated in animal experiments by influencing Th2 cell activation with chamomile oil, which could also prevent the progression of atopic dermatitis in humans. Chamomile oil inhibited IgE or IgG1 overproduction, as well as IL-4 production by Th2 cells. Furthermore, a reduction in histamine release from mast cells was shown. This resulted in relieved itching and decreased scratching in the mice. It is currently unclear which components of the oil contribute to alleviating atopic dermatitis-like immunological and skin changes in mice [110]. A recent in vitro study showed that the anti-inflammatory effect of chamomile oil involved immune cell modulation in mice and humans. The essential oil inhibited M1 macrophages and upregulated endogenous antioxidant defense systems. It induced NRF2 and inhibited NF-κB and may also act on human CD4+ T cells of the adaptive immune response. However, further in vivo studies are needed [114].

Other activity

Although studies reported the anticancer effects of chamomile extract in vitro [115], [116], fewer studies have been published on the antitumor activity of chamomile essential oil. In a recent investigation, chamomile oil showed significant inhibition of proliferation, migration, and invasion of a TNBC (triple negative breast cancer) cell line, which was believed to be due to inhibition of the PI3K/Akt/mTOR signaling pathway. However, further studies in vitro and in vivo would be necessary for the therapy of TNBC, whereby low toxicity and good tolerability could be achieved [117]. One study reported an anxiolytic effect of α-bisabolol on mice. At low doses, locomotor activity was not affected, but at higher doses, it had a sedative effect and negatively influenced motor coordination. α-Bisabolol seems to act anxiolytically through interaction with the GABA_A receptor. Here again, further investigation with chronic administration are required to substantiate this assumption and clarify the mechanism of action [118].

Clinical trials investigated chamomile essential oils as a therapeutic agent in psychiatric issues, such as anxiety disorders, depression, sleep disorders [119], or stress [67], and showed a positive, significant influence on the examined diseases [67], [119]. Furthermore, chamomile essential oil is used in obstetrics. In a randomized controlled trial, chamomile oil was used with massages, which increased maternal satisfaction and reduced labor pain scores [120]. Another randomized, double-blind clinical trial investigated the effect of chamomile essential oil on cesarean section pain in primiparous women, resulting in reduced pain and reduced need for pain relievers [121]. Moreover, in orthopedic issues, topical application of chamomile oil had a positive effect on patients with knee osteoarthritis [122] and patients with mild to moderate [123], as well as severe [124] carpal tunnel syndrome. Even local application on the lower back led to an improvement of symptoms [125]. In addition, the application of chamomile oil was successfully examined on patients suffering from migraine [126]. Several studies indicated safe use and no side effects or complications using chamomile oil [121], [122], [126].

Rose oil

Rose oil is the essential oil extracted from Rosa x damascena, also known as damask rose, which is a hybrid between R. gallica and R. phoenicia and belongs to the Rosaceae family [127]. R. damascena is one of the 200 species of the genus Rosa [128]. It is a perennial plant with large pink flowers that grows up to 2.5 meters in height and is native to Europe and the Middle East but originated from Iran [127], [128], [129]. Rose essential oil has been isolated from R. damascena since 700 AD in Iran [128]. Today, the leading producers of rose oil are Bulgaria, Turkey, China, Russia, Egypt, Morocco, Iran, and India [127], [130], [131], but the best quality oil was reported as the Bulgarian rose oil [128]. The petals contain only about 0.03% of essential oil, which makes it one of the most expensive essential oils in the world [128], [132]. The highest oil content in R. damascena seems to be obtained when moderate temperatures and moist air are provided during the flowering period [133]. The harvest period is from the second half of May to the end of June, with cooler seasons increasing the essential oil content in the collected flowers. For oil production, only fresh flowers are used, which are picked by hand early in the morning and should be distilled soon, as fermentation through storage reduces the oil content. However, fermentation for a short time is acceptable, as this increases the citronellol content, which should be at least 35% [132].

It is important to distinguish between rose essential oil, rose water or hydrosol, and rose absolute, as they show different constituents and pharmacological activities. Essential oil and hydrosol are produced during the distillation procedure, the hydrosol being a by-product. The absolute is derived from extracting the concrete with ethanol during solvent extraction [130]. Those three commercial products differ in price, with the essential oil being the most expensive due to its low yield [129]. Three thousand parts of flowers supply the one part of the essential oil that retains the main constituents citronellol and geraniol ([Fig. 1 l]), responsible for biological activities [128]. Rose absolute is obtained from the semi-solid, waxy concrete from solvent extraction by dissolving it in alcohol, precipitating and filtering the waxes by cooling, and evaporating the alcohol by vacuum. With 0.22 – 0.25%, the yield of rose concrete is higher than the yield of the rose essential oil: 400 parts of flowers yield one part of concrete. The yield of rose absolute is about 62 – 65%, which is the highest. The main component of rose absolute is water-soluble phenylethyl alcohol ([Fig. 1 m]; 60 – 75%), which is much less contained in the lipophilic essential oil. However, the odor of the concrete is most reminiscent of the true scent of rose petals due to this hydrophilic composition [134]. Another difference is the color of the products. Rose essential oil is yellow, rose water is colorless, and rose absolute is orange-red [127]. Rose water holds 0.02 – 0.09% essential oil, highly worshiped due to relaxing and calming effects in Iran [128]. Furthermore, antiseptic, antioxidant, antiphlogistic, analgesic, laxative, and anti-aging properties were reported [128], [135]. In addition, rose water is a prevalent food additive [136].

A search request with “Rosa damascena AND essential oil” on pubmed.ncbi.nlm.nih.gov resulted in 40 results in the last 10 years (accessed on 21.09.2023 22 : 59). Concerning psychiatric issues like anxiety, depression, stress [137], and insomnia [138], meta-analyses are available. Furthermore, pain [139] and sexual dysfunctions [140], [141] are research topics. The way of application differs in clinical studies. Inhalation aromatherapy [142], [143], oral intake [140], [141], and topic local application [144] seem to be the most common methods of application.

Chemical composition of rose essential oil, absolute, and hydrosol

The essential oil of petals from R. damascena contains monoterpene alcohols (citronellol, geraniol, linalool, and nerol), monoterpene esters (geranyl acetate and citronellol acetate), alcohols (phenylethyl alcohol), phenols (eugenol ([Fig. 1 n])), phenyl ether (methyl eugenol), aliphatic monoterpenes (α-pinene and β-myrcene), alkanes (9-nonadecane, nonadecane, heptadecane, and heneicosane), and alkenes (nonadecene) [129]. [Table 3] shows a comparison of the relative percentages of the main compounds of rose essential oil, absolute, and hydrosol [129]. This example illustrates the importance of distinguishing between the three products, as the compositions strongly differ. The essential oil from rose petals mainly consisted of citronellol (35.23%), followed by geraniol (22.19%), nonadecane (13.85%), and nerol (10.26%). In rose absolute, phenylethyl alcohol clearly predominated (78.38%), while citronellol is obtained in much lower concentration than in the essential oil (9.91%), as well as nonadecane (4.35%) and geraniol (3.71%). The hydrosol mainly contained geraniol (30.74%) and citronellol (29.44%), followed by phenylethyl alcohol (23.74%) and nerol (16.12%) [129]. Another study reported the significant components of the essential oil to be citronellol (23.5 – 47.5%), nonadecane (0 – 39.7%), geraniol (0 – 18%), and heneicosane (0 – 17.5%) [133] ([Table 3]). As described above, discrepancies in composition can be ascribed to ecological factors, genotype, the development stages of the blossoms in the moment of picking, extraction method, and storage conditions [128], [133], [145].

Table 3 Comparison of the main contents of two R. damascena oils, an absolute and a hydrosol [129], [133].

Components	Rose oil (%)		Rose absolute (%)	Hydrosol (%)
	[129]	[133]	[129]	[129]
Values are given as relative percentages of compounds. The constituents were determined by GC-MS.
Citronellol	35.23	23.55 – 47.43	9.91	29.44
Geraniol	22.19	0 – 18.12	3.71	30.74
Nonadecane	13.85	0 – 39.70	4.35
Nerol	10.26	0 – 1.15	1.43	18.12
Heneicosane	4.85	0 – 17.45
9-Nonadecene	2.79	2.63 – 4.89
Phenylethyl alcohol	2.30	0 – 0.39	78.38	23.70
Geranyl acetate	2.00
Methyl eugenol	1.97	0 – 0.87	0.69	1.52
Eugenol	1.18
Heptadecane	0.90	1.10 – 1.59
α-Pinene	0.80
Citronellol acetate	0.70	0 – 0.13
Linalool	0.53	0 – 0.29
Germacrene-D	0.45

Rose absolute contained β-carotene (422.3 ± 35.6 ppm), α-tocopherol (2397.1 ± 72.5 ppm), and γ-tocopherol (343.1 ± 28.4 ppm) in high concentrations, which makes it a strong natural antioxidant. The essential oil only contained γ-tocopherol in much lower concentration (9.6 ± 0.56 ppm), whereas none of these antioxidant substances were detected in rose hydrosol [129].

The rose ketones β-damascenone, β-damascone, and β-ionone are responsible for more than 90% of the odor of the essential oil of R. damascena. These are formed during degradation of carotenoids (enzymatic or oxidative cleavage) and are present in less than 1% of the oil, but the odor recognition thresholds are low. It is assumed that β-damascenone is formed during steam distillation and is not released from the blossoms of R. damascena [146]. The quality of rose essential oil is determined by a high content of citronellol, while 2-octamine should be obtained as little as possible due to its toxicity [127], [133]. Furthermore, the ratio between citronellol/geranial should be between 1.25 and 1.3 [127]. High-quality rose oil is generally supposed to have a high monoterpene alcohol content and a low alkane content [131]. High phenolic content is found in rose absolute and the essential oil and contributes to the medicinal properties of damask rose, such as free-radical scavenger, anticancer, anti-inflammatory, and antidepressant activities [128], [129]. A study demonstrated that due to the phenolic content, they show intense antibacterial activity against E. coli, B. subtilis, S. aureus, Chromobacterium violaceum, and Erwinia carotovora. The rose absolute was additionally effective against P. aeruginosa, whereas the hydrolate showed no antibiotic activity at all [129].

Investigations on biological activity

Antimicrobial and anti-inflammatory activity

Various components of rose essential oils have different beneficial healing properties [130]. Geraniol, geranyl acetate, eugenol, and nerol showed antibacterial activity against B. subtilis, Enterococcus aerogenes, E. coli, P. aeruginosa, S. aureus, and Yersinia enterocolitica (among others) [147]. In another study, the efficacy of rose damask oil, as well as eugenol and geraniol, was investigated, and antibacterial activity against E. coli, Salmonella enterica, Campylobacter jejuni, and L. monocytogenes was shown [148]. In previous studies, eugenol has demonstrated diverse effects against pathogens and harmful microorganisms. Therefore, some pesticides contain eugenol and methyl eugenol as insect attractants [149]. Geraniol proved an effective mosquito repellent and insecticide impact with low mammalian toxicity and biodegradability. In previous studies, geraniol showed antimicrobial, antioxidant, and anti-inflammatory effects [150].

Citronellol and geraniol have been reported to inhibit ergosterol biosynthesis in fungi, resulting in a loss of cell membrane integrity and functionality in T. rubrum cells, a causative agent of dermatophytosis. In addition, they hindered mycelial growth, conidia germination, and fungal growth on human nail fragments [151]. Furthermore, citronellol and geraniol showed anti-inflammatory activity. TNF-α activates neutrophil granulocytes and leads to their adhesion to an infected lesion through the adhesion molecules CD11b/CD18 as an important role in the defense response. However, excessive inflammatory response can also be triggered by the release of proinflammatory factors by neutrophils, leading to tissue damage. It was demonstrated that citronellol and geraniol suppressed TNF-α-induced adhesion of human neutrophils to plastic sheets in vitro [152]. Another publication reported an anti-inflammatory effect of rose oxide ([Fig. 1 o]), a fragrant in rose oil, in animal experiments by inhibiting IL-1β production and leukocyte migration. However, the exact mechanism of action is not known [153].

Phenylethyl alcohol smells very floral and is popular in the flavor and fragrance industries. However, it could also be beneficial in cosmetic formulations as a preservative due to bacteriostatic activities and, thus, prevent the products of microbial growth during storage [154]. Some studies attributed phenylethyl alcohol to emit an antibacterial effect [155], such as inhibiting DNA synthesis in E. coli [156]. Another study showed that phenylethyl alcohol negatively affected the structure and permeability of the bacterial cell wall and degraded it to a limited extent, resulting in inhibition of DNA synthesis. Furthermore, the compound was reported to increase the efflux rate of cellular potassium by the energy-dependent potassium pump [157].

Antispasmodic activity

In addition, it was reported that citronellol, geraniol, eugenol, and methyl eugenol showed antispasmodic effects on rat or guinea pig isolated ileum [158], [159], [160]. A stronger inhibition of contraction in the isolated rat ileum by the single compounds geraniol and citronellol compared to the essential oil of R. damascena was demonstrated. The authors concluded that geraniol and citronellol were responsible for the contraction-inhibiting effect of rose oil and, therefore, supported the use of rose water to treat abdominal cramps [158]. Another study showed concentration-dependent and reversible relaxing and antispasmodic effects on rat ileum through direct action on smooth muscle cells rather than indirect release of neurotransmitters. The mechanism of action seems to be an autonomous of changes in resting membrane potential and extracellular Ca²⁺ influx. The authors further suggested that eugenol may be the functional principle for the medicinal efficacy of healing plants in gastrointestinal disorders [159]. Furthermore, concentration-dependent and reversible relaxing and antispasmodic effects by receptor-dependent and -independent mechanisms on guinea pig ileum was shown, which was through direct action on smooth muscle cells rather than indirect release of neurotransmitters. Methyl eugenol was assumed to be the major principle for the medicinal efficacy of healing plants in gastrointestinal disorders [160].

Psychological effects

Clinical studies on the effect of R. damascena oil inhalation or oral intake on psychiatric disorders make up a large proportion of the studies found in the literature. A meta-analysis concluded that the inhalation or oral intake of R. damascena oil influenced state anxiety, depression, and stress positively [137]. Even in exceptional situations, damask rose oil decreased state anxiety and improved sleep, as a randomized controlled trial on inhalation aromatherapy in operating room personnel reported during the COVID-19 pandemic [142]. Even in invasive medical intervention, another kind of exceptional situation, inhalation aromatherapy with R. damascena oil, had a significant effect on stress and anxiety, which influenced hemodynamic parameters positively [143]. Another meta-analysis concluded that R. damascena oil (inhalation aromatherapy/oral intake) improved adultsʼ sleep quality [138].

In addition, it is assumed that contents of R. damascena oil probably affect the hypothalamic–pituitary–gonadal axis, leading to hormone shifts, which counteract one of the underlying mechanisms of sexual dysfunction [161]. Opioid substitution therapy influences this hormone axis in favor of sexual dysfunctions [141]. Hence, studies investigated the effects of damask rose oil on patients with opioid use disorder treated with maintenance therapy. Females treated with methadone suffering from sexual dysfunction benefited from orally taken R. damascena oil, which resulted in improved sexual function, increased happiness, and a positive shift of female sexual hormones [141]. A similar study investigating males with opioid disorder and maintenance therapy and the influence of the essential oil of R. damascena resulted in improved sexual function and a positive influence on testosterone levels [140]. Furthermore, patients with an opioid disorder seemed to benefit from therapy with R. damascena oil, particularly male patients treated with selective serotonin-reuptake inhibitors, in which sexual dysfunctions are a noteworthy side effect [162].

R. damascena oil was also investigated regarding pain-relieving effects. Aromatherapy with damask rose had a positive effect on reducing acute pain, as a meta-analysis demonstrated. However, insufficient evidence for safety and efficacy was criticized [139]. Aromatherapy with the oil showed favorable effects on pain severity and anxiety in the first stage of labor among nulliparous women, as a randomized controlled trial reported [163]. Moreover, local application of R. damascena oil reduced lower back pain and positively affected the functional ability in pregnant women. In addition, it was pointed out that the application had no significant adverse effect [144]. Topic application of R. damascena oil in patients with migraine may also help patients with certain syndromes but had no significant effect on pain intensity or photophobia [164].

Jasmine oil and absolute

Jasmine oil and absolute are obtained from the flowers of the popular aromatic shrub Jasminum grandiflorum (Spanish jasmine), which belongs to the Oleaceae family and is cultivated commercially for its pleasant fragrant blossoms [165], [166]. The jasmine genus includes about 2000 species worldwide, with 40 species found in India [167], [168], [169]. Since antique times, Jasminum species have been among Indiaʼs most favored fresh-picked blossoms [170]. The summer-blooming species J. grandiflorum is native to Africa (Djibouti, Eritrea, Ethiopia, Somalia, Sudan, Kenya, Uganda, and Rwanda) and Asia (Oman, Saudi Arabia, Yemen, India, and Pakistan) and is cultivated in Africa (Egypt and Morocco), India, and France [168], [171]. The blossoms taste acrid-bitter with a sharp flavor [172].

Another species commonly cultivated in India is J. sambac, although its blossoms and fragrance differ significantly. The petals of J. grandiflorum are more delicate, and the fragrance is described as intensely floral, warm, and very diffuse, while the petals of J. sambac are heavier, robust, thick, and waxy with a sweet, fruity, and sultry scent [165], [173].

Jasmine flowers bloom all year round, yet the primary harvest season of J. grandiflorum is reported to be from March to July [165], while another study claimed that in India it typically endures from June to November and peaks in late July to September [173]. Jasmine absolute is produced mainly from delicate blossoms, selected early in the day (6 a. m.) to preserve the fragrance [165], [173]. To obtain 1 kg of jasmine absolute, 600 kg of J. grandiflorum flowers are needed, with 11 000 to 12 000 flowers weighing 1 kg [173]. The control of the release of fragrance molecules from flowers follows an internal circadian clock of the plants, J. grandiflorum emitting the greatest amount at night and accumulating the most significant amounts in the late bud stage. Furthermore, the biosynthesis of volatile aroma compounds such as aromatic alcohols and monoterpene alcohols occurs in the floral tissue, where they are stored mostly in nonvolatile glycosylated form. When flowers open, they are enzymatically hydrolyzed and released as a fragrance to attract pollinators [166].

In Indian Ayurvedic herbal medicine, the leaves and blossoms of J. grandiflorum play a vital role in the treatment of toothache, stomachache, earache, skin diseases, ulcers, ulcerative stomatitis, wounds, dysmenorrhea, and sexual impotence [167], [171]. The leaves can be chewed to treat ulcers in the mouth, or the fresh juice is used for corns due to the salicylic acid content in the leaves [174].

Jasmine absolute is the most important product from J. grandiflorum and is considered valuable in the perfume industry [171]. It has been mentioned as an essential ingredient in perfumes since about 1700 and is contained in some well-known perfumes today, such as the heart note in Chanel No. 5, which has been on the market since 1921 [168]. Its consistency is liquid to viscous, and the color is light orange to reddish-brown. The fragrance is intense floral and lasts for a long time [171]. The central producing countries of J. grandiflorum absolute are India, China, Egypt, Turkey, and Morocco [171], [173]. It is also very popular in aromatherapy for its antidepressant, aphrodisiac, euphoric, relaxing, and stimulating effects [175].

Chemical composition of jasmine essential oil and absolute

Blossom extracts contain carbonic acid esters (benzyl acetate ([Fig. 1 p]), benzyl benzoate, benzyl salicylate, methyl salicylate, (Z)-3-hexenyl benzoate, (Z)-3-hexenyl acetate, and methyl anthranilate), monoterpene alcohols (linalool), monoterpene esters (geranyl acetate), sesquiterpenes (α-farnesene ([Fig. 1 q]), β-farnesene, δ-, γ-cadinene, caryophyllenes, and germacrene D ([Fig. 1 r])), sesquiterpene alcohols (α-cadinol ([Fig. 1 s]), τ-cadinol, τ-muurolol, neridol, and farnesol), diterpene alcohols (phytol ([Fig. 1 t]), isophytol, geranyl linalool), fatty acids and their methyl esters (palmitic acid, stearic acid, and oleic acid), alcohols ((Z)-3-hexenol, benzyl alcohol, and cinnamyl alcohol), aromatic heterocyclic amines (indole), cyclopentenones ((Z)-jasmone ([Fig. 1 u])), oxylipines ((Z)-jasmonate), alkanes (5-methyl tricosane, tetracosane, tetradecane, hexadecane, and nonadecane) and mixed hydrocarbons [165]. The extraction method used affects the chemical composition and fragrance of the isolate, especially in the case of jasmine flowers [168]. Steam distillation is unsuitable for the extraction of jasmine flowers because their many thermolabile constituents are degraded, or some polar compounds are lost [165], [171]. Merely small amounts of an essential oil of poor odor quality are obtained by this method. Thus, in terms of smell, the J. grandiflorum essential oil and the absolute are very different, so that jasmine essential oil is actually of no commercial value [168]. Solvent extraction with hexane or supercritical fluids such as CO₂ is more suitable and used in jasmine oil production to obtain fragrant volatiles [171]. In solvent extraction, n-hexane or n-pentane is added to the blossoms to produce the concrete, containing volatile scent molecules and undesirable lipophilic constituents such as pigments and fatty acid esters that can affect the pharmacological properties. It is also important to mention that volatile constituents may be entrained during the solvent removal step, or solvent residues may remain. A better option would be the production by enfleurage, which is, however, very labor-intensive and unsuitable for industrial scale. The use of supercritical CO₂ extraction proved to be advantageous due to the low extraction temperature [165].

[Table 4] shows the composition of J. grandiflorum flower essential oil compared to its absolute, with the data from different publications. In one study, the absolute derived from flowers harvested in Delhi, India, yielded 0.27%, which was much higher than the essential oil with 0.05% [165]. (E,E)-α-Farnesene, benzyl acetate, and (Z)-3-hexenyl benzoate were the most abundant, both in the essential oil and in the absolute and, together with indole, methyl anthranilate, (Z)-jasmone, (Z)-methyl jasmonate, and (Z)-methyl epi-jasmonate, were liable for the high diffusivity of the jasmine odor [165]. The major component of the essential oil was (E,E)-α-farnesene, followed by benzyl acetate, (Z)-3-hexenyl benzoate, α-cadinol, linalool, and δ-cadinene, while die major component of the absolute was (Z)-3-hexenyl benzoate, followed by (E,E)-α-farnesene, benzyl acetate, linalool, (Z)-3-hexenyl acetate, methyl linoleate, and methyl anthranilate. The absolute generally consisted of more oxygenated monoterpenes and polar compounds (C < 11) (16.2%) than the essential oil, more benzene (37.8%), more sesquiterpene hydrocarbons (21.1%), fewer oxygenated sesquiterpenes and polar compounds (5.7%) but many more fatty acids/esters (9.8%) and long-chain hydrocarbons (4.2%), the latter not being detected in the essential oil at all. In contrast, τ-cadinol (4.5%) and α-cadinol (7.2%) were present in relatively high proportions in the essential oil, whereas in the absolute they were not at all or hardly at all found. Therefore, it can be concluded that these structures were artifacts from the corresponding glycosides, formed during distillation. The same study also examined a flower extract prepared by supercritical CO₂ extraction and reported that this method produced the most beneficial product. There were mainly (Z)-3-hexenyl acetate (5.5%), linalool (9.6%), benzyl acetate (12.0%), methyl anthranilate (3.1%), (E,E)-α-farnesene (20.0%), and (Z)-3-hexenyl benzoate (24.8%) detected in the extract. It also had more significant amounts of compounds relevant to the fragrance properties of the extract, such as methyl salicylate (0.3%), indole (0.3%), (Z)-jasmon (0.2%), (Z)-methyl jasmonate (0.2%), and (Z)-methyl epi-jasmonoate (0.3%). The liquid CO₂ extract had the finest jasmine scent because it was enriched with volatiles and it was free of solvent residues [165]. A further study reported the major essential oil compounds to be benzyl acetate (32.4%), (Z)-nerolidol (11.9%), and (Z)-jasmone (8.5%) ([Table 4]) [176].

Table 4 Comparison of the chemical composition of two J. grandiflorum essential oils and absolutes [165], [169], [176], [177].

Components	Essential oil (%)		Absolute (%)
	[165]	[176]	[165]	[177]	[169]
Essential oil (%)		Absolute (%)
[165]	[176]	[165]	[177]	[169]
Values are given as relative percentages of compounds. Essential oils were extracted by liquid CO2 extraction [165] and hydro-distillation [176]. Constituents in [165], [169], [176], [177] were determined by GC-MS.
(E,E)-α-Farnesene	26.2 ± 0.6	7.6	17.0 ± 0.4	1.1	1.1
Benzyl acetate	18.3 ± 0.5	32.4	11.3 ± 0.3	15.5	23.7
(Z)-3-Hexenyl benzoate	12.2 ± 0.6	1.1	22.0 ± 0.6	0.9	0.9
α-Cadinol	7.2 ± 0.3		0.7 ± 0.1
Linalool	7.1 ± 0.3	3.6	8.1 ± 0.3	4.5	8.2
δ-Cadinene	5.7 ± 0.3		0.5 ± 0.1
τ-Cadinol	4.5 ± 0.3
(Z,E)-α-Farnesene	2.5 ± 0.3		1.0 ± 0.2	0.1
Methyl linoleate	1.2 ± 0.2		3.0 ± 0.3	0.2	2.8
Hexyl benzoate	1.2 ± 0.2
(Z)-Caryophyllene	0.8 ± 0.2	6.2
Germacrene D	0.8 ± 0.2		1.9 ± 0.2
Methyl palmitate	0.6 ± 0.1		1.6 ± 0.2		1.4
Benzyl benzoate	0.4 ± 0.1	7.4	0.6 ± 0.1	11.4	20.7
τ-Muurolol	0.4 ± 0.1		0.6 ± 0.1
(E)-Caryophyllene	0.4 ± 0.1
Benzyl salicylate	0.3 ± 0.1	2.5	0.1	0.2
Methyl anthranilate	0.3 ± 0.1	2.5	3.0 ± 0.3
(Z)-3-Hexenol	0.3 ± 0.1		0.4 ± 0.1
(E)-β-Farnesene	0.2 ± 0.1		0.5 ± 0.1
Methyl salicylate	0.2 ± 0.1		0.1	0.1	0.08
Indole	0.2 ± 0.1		0.1	2.6	1.8
Benzyl alcohol	0.2 ± 0.1		0.3 ± 0.1	0.7	1.3
(E)-Nerolidol	0.2 ± 0.1			0.1	0.3
(Z)-Nerolidol	0.1	11.9	2.0 ± 0.3
(Z)-Jasmone	0.1	8.5	< 0.1	1.5	1.9
Methyl stearate	0.1		0.9 ± 0.3	0.3
(Z)-3-Hexenyl acetate	< 0.1		6.3 ± 0.2		0.01
(E)-3-Hexenyl acetate	< 0.1		1.2 ± 0.2
5-Methyl tricosane			1.8 ± 0.3
Stearic acid			1.8 ± 0.3
Methyl linolenate			1.2 ± 0.4	2.3
Tetracosane			1.2 ± 0.3
Palmitic acid			1.0 ± 0.2
Mixed hydrocarbons			0.8 ± 0.3
(E,E)-Farnesol			0.8 ± 0.2
(E,Z)-Farnesol			0.5 ± 0.1
(E,E)-Farnesyl acetate			0.5 ± 0.1
(Z)-Methyl jasmonate		1.8	0.1		0.6
(Z)-Methyl epi-jasmonate		1.6	0.1
Geranyl acetate			0.1
Hexadecane		1.3	0.1
Nonadecane		1.2	0.1
Phytol		3.5		10.9	10.9
Isophytol				8.0	5.5
Heneicosane		3.4
2,3-Epoxy squalene				11.7

In another J. grandiflorum flower absolute sample from India, the main constituents determined were benzyl acetate (23.7%), benzyl benzoate (20.7%), phytol (10.9%), linalool (8.2%), isophytol (5.5%), geranyl linalool (3.0%), methyl linoleate (2.8%), and eugenol (2.5%) [169]. In the third absolute sample from India listed in [Table 4], benzyl acetate (15.5%), 2,3-epoxy squalene (11.7%), benzyl benzoate (11.4%), phytol (10.9%), isophytol (8.0%), and phytyl acetate (6.0%) were obtained as the major compounds [177]. Another study reported the main constituents of the essential oil from J. grandiflorum flowers from Slovakia to be benzyl acetate (37%), benzyl benzoate (34.7%) and linalool (9.6%), (Z)-jasmone (5%), isophytol (3.3%), and eugenol (2.1%) [178], which was quite different from the essential oils in [Table 4]. This differences in the chemical compositions are probably due to the different geographical areas or harvest periods of the blossoms [165].

Investigations on biological activity

The search for clinical studies concerning J. grandiflorum yielded only a few results, mainly preclinical investigations. Unfortunately, there is also much unserious literature on the jasmine plant, so often, only the extract is reported, without distinguishing between the essential oil or the absolute, which, however, makes a big difference from the ingredients and, thus, properties [168]. In addition, some studies investigated the biological effects of the essential oil [178], while another review claimed that jasmine essential oil had no commercial value [168]. There are only a few studies reporting on the properties of J. grandiflorum absolute extracted from blossoms. However, this review will discuss only the effects of J. grandiflorum flower extracts, essential oil, and absolute.

J. grandiflorum oil decreased neuroinflammatory processes and oxidative stress responses, which may result in inhibited overactivation of microglia. Thus, the essential oil could be a potential agent in the treatment of neuroinflammation-related disorders like Alzheimerʼs disease [179]. Another study reported that boiling water and hydromethanolic flower extracts of J. grandiflorum inhibited the enzymes acetylcholinesterase and butyrylcholinesterase due to phenolic compounds, which is important in the treatment of Alzheimerʼs disease. However, the extracts were much weaker in their activity than the known Alzheimerʼs agent galanthamine. The extracts also showed inhibition of the enzyme monoaminooxidase-A (MAO-A), which plays an important role in the treatment of depression, again in a much weaker extent compared to MAO-A inhibitor clorgyline. By inhibiting MAO-A, the extracts can also inhibit H₂O₂ production, therefore prohibiting oxidative cell damage [180].

The antioxidant activity of J. grandifolium flower essential oil was classified as high with an inhibition of 58.47% as measured by the DPPH method. Furthermore, the antimicrobial activity was determined, which was classified as rather weak, with inhibition zones ranging from 2.33 to 5.33 mm. The MIC was lowest against Candida glabrata (MIC₅₀: 0.65 µL/mL; MIC₉₀: 0.97 µL/mL) and highest against S. aureus, S. pneumoniae, and P. aeruginosa (MIC₅₀: 11.36 µL/mL; MIC₉₀: 15.26 µL/mL) [178]. However, the vapor phase of the essential oil exhibited more potent antimicrobial activity on foods such as apples, pears, carrots, and mild radishes than the contact application due to the significant number of volatile compounds. Furthermore, it had less impact on the sensory properties of the items, which offers the possibility of using vapor phase jasmine essential oils for food preservation. Additionally, the study demonstrated an insecticidal activity of the essential oil against Oxycarenus lavatera and Brassicogethes aeneus. From a concentration of 12.5%, it could be inhibited by more than 50%. Thus, J. grandiflorum flower essential oil could represent a natural, environmentally friendly, effective, and relatively safe insecticide, although synthetic repellents are currently favored [178].

Since clinical and preclinical studies on jasmine essential oil are very limited, investigations on the flower extract will be mentioned at this point. In an in vivo study on rats, an extract of J. grandiflorum was found to be effective against cisplatin-induced nephrotoxicity. By affecting several molecular pathways and reducing cisplatin-induced gene expression, it has been found that contents of J. grandiflorum extract counteracted cisplatin-induced nephrotoxicity [181]. In another preclinical study, the extract was suggested to be an effective remedy to treat gastric ulcerations [182]. Furthermore, J. grandiflorum leaves, flowers, and roots have been reported to show wound-healing properties, with the leaves having the greatest potential [183]. However, one study showed that topical treatment with the flower ethanol extract in rats resulted in wound contraction, thus shrinkage of the wound area, and increased hydroxyproline content of granulation tissue, the main component of collagen that provides strength to the tissue [172].

Neroli oil

Neroli essential oil is obtained from the flowers of the bitter orange tree (Citrus x aurantium), which belongs to the Rutaceae family [184]. The bitter orange (C. aurantium) is also called sour orange and is a hybrid from C. maxima (pomelo) and C. reticulata (tangerine). It originates from Southeast Asia but is now found throughout the Mediterranean region and grown in India and America. The plant prefers subtropical and near-tropical climates and is very hardy and able to persist in poor soil conditions [185]. Three different types of essential oils can be obtained from the bitter orange plant. An essential oil called petitgrain is obtained by steam distillation from the leaves and tiny buds of the green fruits, while the oil obtained by steam or water distillation of the blossoms is called neroli. The third essential oil is received by the cold pressing of the peel of the fruit [186]. The three different products vary in color, fragrance, and chemical composition. Petitgrain oil is pale yellow, smells woody, and consists mainly of linalyl acetate (45%), geranyl acetate, linalool, and geraniol. Neroli oil is pale or dark yellow and contains mainly linalool, linalyl acetate, and limonene. The cold-pressed peel oil is yellowish-brown, smells fresh floral, and includes a very high proportion of limonene (up to 90%) [185].

The European Pharmacopoeia (10th edition, 2020, p. 2326 – 2327) describes neroli oil as a clear, pale, or dark yellow essential oil with a characteristic odor, obtained from fresh flowers of C. aurantium by steam distillation. The odor of the essential oil is described as pleasant floral, green, methyl-like, and honey-like [184] or slightly bitter-sweet and floral [185]. However, since only tiny quantities of essential oil can be obtained by distillation – one ton of fresh bitter orange flowers yields one kilogram of pure neroli oil – it is one of the most expensive essential oils in the world, with an estimated production volume of 4.5 – 6.5 tons per year [184], [187]. Cheaper products with a very similar odor to neroli oil have been developed and are often found on the market as adulterations of the genuine oil [188]. Neroli oil is produced in many countries, such as Algeria, Morocco, Egypt, France, and Spain. However, the oil manufactured in Tunisia is reported to be the best and most expensive and has a considerable economic value for the country [187]. The blossoms must be picked by hand early in the morning, with the flowering period between the end of April and the beginning of June. They are distilled with water or steam, yielding between 0.08% and 0.13% of the oil. High labor costs and reduced acreage of bitter oranges led to a decreasing production rate in the European Mediterranean region [188]. Weather and temperature conditions throughout the year affect the quality of neroli oil [184]. Rose, jasmine, and neroli are the three most popular aromatic flowers in perfumery and are often called the “three pearls of perfumery” [188]. In addition to in the perfume industry, jasmine flowers are also used in teas and the food industry, where neroli essential oil is utilized in liqueurs [189]. Orange floral water, the by-product of the distillation process, is used to flavor sweets [189]. Furthermore, the flower water is traditionally used in Tunisia as a cardiac stimulant and carminative, as well as a sleep aid for infants [187]. C. aurantium oil is very common in aromatherapy [190].

Chemical composition

Neroli oil mainly contains monoterpenes (β-pinene, limonene, (E)-β-ocimene, sabinene, myrcene, α-pinene, (Z)-β-ocimene, α-terpinolene, γ-terpinene, and 3-δ-carene ([Fig. 1 v])), monoterpene alcohols (linalool, α-terpineol, geraniol, nerol, and terpinene-4-ol), monoterpene esters (linalyl acetate, geranyl acetate, neryl acetate, and terpinyl acetate), monoterpene oxides (linalool oxide), sesquiterpenes (β-caryophyllene and δ-germacrene), sesquiterpene alcohols ((E)-farnesol and (E)-nerolidol), and anthranilic acid ester (methyl anthranylate) [189]. The chemical composition differs widely depending on the country of origin. The main components of neroli oils from four different countries, as well as the defined limits according to the European Pharmacopoeia, are listed in [Table 5], describing that none of the oils fully complied. Greek neroli oil contained too much β-pinene (19.1%) and (E)-farnesol (5.1%) [189]. The oil from Cyprus contained far too little linalool (14.1%), β-pinene (2.4%), and limonene (5.8%); geranyl acetate and methyl anthranilate were not detected [191]. The essential oil from Tunisia did not correspond at all to the pharmacopoeia [192]. Some Egyptian oils were almost equivalent, but all contained too little β-pinene (1.9 – 3.7%), and the content of (E)-nerolidol was not given [188].

Table 5 Chemical composition of essential oils of C. aurantium from four different countries [188], [189], [191], [192] in comparison with the European Pharmacopoeia standards (10th edition, 2020, p. 2328).

Components	Greece (%) [189]	Cyprus (%) [191]	Tunisia (%) [192]	Egypt (%) [188]	PhEur (%)
Values are given as relative percentages of compounds. Constituents were determined by GC-MS. PhEur = European Pharmacopoeia
Linalool	29.14	14.12		43.69 – 53.33	28.0 – 44.0
β-Pinene	19.08	2.43		1.89 – 3.70	7.0 – 17.0
Limonene	12.04	5.8	27.5	7.87 – 11.89	9.0 – 18.0
(E)-β-Ocimene	6.06	2.31	4.3	3.31 – 5.11
(E)-Farnesol	5.14	1.63	8.0	1.17 – 2.03	0.8 – 4.0
α-Terpineol	4.56	4.87	14.0	4.89 – 6.22	2.0 – 5.5
Geraniol	4.31		0.3	2.94 – 3.83
Linalyl acetate	3.88	4.53		2.19 – 14.57	2.0 – 15.0
Geranyl acetate	2.59			3.01 – 3.08	1.0 – 5.0
Sabinene	2.01		0.5	0.85 – 1.56
(E)-Nerolidol	1.76	4.41	17.5		1.0 – 5.0
Myrcene	1.59	1.61	0.3	1.33 – 1.74
α-Pinene	1.35		0.2	0.15 – 0 – 26
Neryl acetate	1.30	2.50		1.43 – 1.45	≤ 2.5
Nerol	0.83	1.51		0.95 – 1.28
(Z)-β-Ocimene	0.77		0.8	0.47 – 0.61
Terpinen-4-ol	0.68		0.4	0.44 – 0.79
α-Terpinolene	0.47			0.26 – 0.43
β-Caryophyllene	0.42	1.25	0.1	0.56 – 0.94
γ-Terpinene	0.36		0.3	0.11 – 0.28
Linalool oxide	0.29			0.13 – 0.25
Terpinyl acetate	0.20		11.7	0.05 – 0.07
Methyl anthranylate	0.19		1.2	0.04 – 0.12	0.1 – 1.0
3-δ-Carene	0.17		2.4	0.03 – 0.09
δ-Germacrene	0.13		0.7	0.03 – 0.08

Investigations on biological activity

Antioxidant activity

The antioxidant activity of neroli oil has been studied several times. One study reported the highest antioxidant activity of the essential oils in old leaves, followed by the flowers, young leaves, and peel, with antioxidant potential determined by DPPH assay. Authors claimed that citrus essential oils could help prevent oxidation as an antioxidant and free-radical scavenger [189]. Another investigation described a very high antioxidant activity of the essential oil of C. aurantium flowers, even higher than that of the standard antioxidant ascorbic acid in a DPPH test [192]. A further study confirmed moderate DPPH radical scavenging and H₂O₂ scavenging activities, with the flower essential oil having lower activities than the flowersʼ ethanol extract. However, the antioxidant activities of essential oil and ethanol extract due to high proportions of monoterpenes and sesquiterpenes, which have similar antioxidant activity to phenolic compounds, were lower (p ≤ 0.05) than those of ascorbic acid and quercetin standards [191]. In contrast, another study published low ABTS free-radical scavenging activity of neroli oil. Authors explained these findings with the high content of limonene, which showed neglectable low ABTS-radical scavenging activity. y-Terpinene would elicit antioxidant activity but was present in too little amounts in neroli oil [187]. It is important to mention that the antioxidant activity of a natural product is mostly explained by the synergism, antagonism, and additivity of different compounds [187].

Antimicrobial activity

More publications demonstrated the antimicrobial potential of the essential oil extracted from C. aurantium flowers in vitro. A study discovered the high antibacterial activity of neroli oil against E. coli (MIC: 781 µL/mL), Salmonella typhimurium (MIC: 1562 µL/mL), S. aureus (MIC: 391 µL/mL), Bacillus cereus (MIC: 781 µL/mL), and L. monocytogenes (MIC: 391 µL/mL), with Gram-positive bacteria being more sensitive to neroli oil than Gram-negative germs [191]. Gram-negative bacteria may be more resistant to hydrophobic plant essential oils due to the hydrophilic polysaccharide chain in their outer membrane [192]. According to the literature, the antimicrobial activity of the essential oil is due to the presence of constituents such as β-pinene, linalool, α-terpineol, β-myrcene, and limonene [185]. The potent antimicrobial activity was further ascribed to high percentages of hydrocarbons, monoterpenes, and oxygenated monoterpenes. Moreover, antibacterial activity in vitro against Gram-positive bacteria such as B. subtilis (MIC: 2.5 µL/mL), B. cereus (MIC: 0.625 µL/mL), S. aureus (MIC: 0.312 µL/mL), Staphylococcus epidermis (MIC: 1.25 µL/mL), E. faecalis (MIC: 1.25 µL/mL), Micrococcus luteus (MIC: 2.5 µL/mL), L. monocytogenes (MIC: 0.312 µL/mL) and Gram-negative bacteria such as S. enteritidis (MIC: 0.625 µL/mL), E. coli (MIC: 1.25 µL/mL), P. aeruginosa (MIC: 2.5 µL/mL), and K. pneumoniae (MIC: 2.5 µL/mL) was reported [192]. Synergistic effects of the essential oilsʼ various central and minor components seem to play a major role [191]. Another study reported pronounced antibacterial activity of neroli oil, especially against P. aeruginosa, as well as powerful antifungal activity compared to nystatin, with limonene, (E)-nerolidol, and (E,E)-farnesol mainly responsible for the antifungal effect [185], [187]. All above-mentioned studies consider neroli essential oil as a promising natural preservative in the food industry for the future.

Other activity

The essential oil of C. aurantium flowers caused a reduction in abdominal constriction in mice when injected intraperitoneally by interfering with prostaglandin synthesis. Furthermore, the involvement of the nitric oxide (NO) pathway in the analgesic effect of the oil was evidenced, which affects cereptive processing in the peripheral and central nervous systems. The analgesic effect was shown to be due to the presence of linalool in neroli oil. However, linalyl acetate, nerolidol, farnesol, α-terpineol, or limonene could also be involved in the effect [193]. Previous studies have demonstrated that R-(+)-limonene, a major compound in neroli oil, had an antinociceptive effect in mice due to inhibiting the synthesis of inflammatory mediators rather than interaction with opioid receptors [194]. α-Terpineol also showed a reduction in nociceptive behavior in several pharmacological experiments in mice and was characterized as the compound responsible for the analgesic effect of essential oils [195]. Neroli oil also demonstrated activity against acute and chronic inflammation, with the involvement of arachidonic acid metabolites and inhibition of NO production considered the mechanism of action. Linalool and the corresponding acetate in the essential oil seem to play a fundamental role in the anti-inflammatory effect, probably inhibiting the biosynthesis of prostaglandins [193].

Neroli oil induced vasodilatation in animal experiments by relaxing vessels via action on the vascular endothelium via the NO-sGC pathway but mainly via action on the vascular smooth muscle by reducing intracellular calcium (Ca²⁺) concentration, attenuating vascular contraction. It inhibited extracellular Ca²⁺ influx via a cation channel and a store-operated Ca²⁺ entry mechanism mediated by the RyR pathway [196]. Furthermore, an antagonizing effect of linalool was found on extracellular Ca²⁺-dependent contraction in mesenteric arteries, thus reducing blood pressure [197]. In an in vivo study, the main compounds of neroli essential oil (linalool, linalyl acetate, nerolidol, (E,E)-α-farnesol, α-terpineol, and limonene) were found to have an anticonvulsant effect in mice [198].

Psychological effects

Sedative effects of neroli oil have been reported [199]. Linalool seems to be mainly responsible for the CNS suppressive and anxiolytic effects of neroli oil, which blocks the binding of glutamate to glutamatergic receptors in the CNS and, thus, the activation of glutamatergic receptors, resulting in decreased excitability and reducing anxiety. Furthermore, inhibition of norepinephrine and serotonin receptors, as well as the ability to activate GABA receptors, is thought to cause dissection [186].

Neroli essential oil is a research topic in both clinical and preclinical issues, although only a few studies can be found in the literature. In a randomized controlled trial, the effect of neroli oil aromatherapy at childbirth was investigated. This study concluded that neroli oil aromatherapy decreased anxiety and pain in labor [200]. In addition, the application in acute situations is also likely to have an antianxiety effect, as demonstrated by a double-blind placebo-controlled trial on the effect of neroli oil inhalations in patients with acute coronary syndrome [201]. Another double-blind, randomized study reported that C. aurantium flower distillate may reduce anxiety prior to a minor outpatient surgical procedure in patients who had no experience with surgery or previous hospitalizations [202].

In a meta-analysis, aromatherapy with neroli oil was attributed with the improvement of sexual functions. However, the small number of studies and a need for more standardization was mentioned as limiting [203]. Another randomized controlled trial regarding neroli oil inhalations on menopausal symptoms resulted in positive effects on blood pressure, stress, and sexual desire [204]. In addition, a study on several oils, including neroli, showed that smelling the oils could affect oxytocin levels in postmenopausal women. This may reduce the loss of muscle mass and positively affect quality of life [205]. Furthermore, the effectiveness of aromatherapy with neroli oil on female students with premenstrual syndromes was reported. The intervention significantly reduced psychological but not physical symptoms and social function [206].

Ylang-ylang oil

Ylang-ylang oil is the essential oil extracted by water or steam distillation from the fresh and mature blossoms from the tropical Asian tree Cananga odorata, which belongs to the Annonaceae family [207], [208]. It is in high demand for perfume and soap production in the fragrance industry due to its pleasant scent [209].

C. odorata originally derives from Indonesia and is now grown throughout the Indian Ocean region, with the Union of Comoros, Madagascar, and Mayotte being the central producing countries [208], [209]. The Union of Comoros produces most of the worldʼs ylang-ylang oil of the highest quality, which is of great economic value to the country [209]. C. odorata is also found in nature on many Pacific islands and in Australia and was brought to China, India, Africa, and America [210]. In the 19th century, the well-known British Macassar hair oil was produced to stimulate hair growth and shine by combining ylang-ylang oil and coconut oil. From the 20th century, the oil was traditionally used to treat tropical fevers such as malaria in Java and Vietnam [211], [212]. In Indonesia, ylang-ylang oil is believed to reduce fears and inhibitions during sex and to exhibit a euphoric effect, which is why the flowers are placed on the beds of newlyweds [213]. In India, the essential oil of C. odorata is used to treat headaches, eye inflammation, and gout. In Malaysia, the leaves are rubbed on the skin to treat itching [214].

The word ylang-ylang comes from the Filipino Along-Ilang (“hanging or fluttering object”), referring to the drooping flowers of C. odorata [215]. The tree prefers hot temperatures and rich volcanic soils in rainforest regions. Two months before the rainy season (starting from June), the seeds are sown in nursery beds. Two months after germination, the plantlets, already about 50 cm tall, are planted in the field. Flowers are expected from the fifth year onward, with the main flowering periods reported to be from April to June and from October to December [216]. In the main producing area, the Comoros, 900 – 1500 kg of ylang-ylang blossoms can be harvested from a 1 ha plantation, yielding 18 – 30 kg of the pale to deep yellow essential oil [215], [217]. Due to the pleasant scent of ylang-ylang oil, which is described as delicate, fresh, floral, slightly fruity, and sweet, it is very popular in cosmetic products such as massage oils, shower gels, creams and can be found in scented candles [210].

Chemical composition

The essential oil obtained from C. odorata blossoms contains monoterpenes (α-, β-pinene), monoterpene alcohols (linalool and geraniol), monoterpene esters (geranyl acetate), carbonic acid esters (benzyl benzoate, methyl benzoate, (E)-cinnamyl acetate, benzyl salicylate, and benzyl acetate), ethers (p-cresyl methyl ether), sesquiterpenes ((E,E)-α-farnesene, α-humulene ([Fig. 1 w]), germacrene D, α-muurolene, γ-cadinene, and β-caryophyllene), sesquiterpene alcohols (τ-cadinol, farnesol, and τ-muurolol), sesquiterpene esters ((E,E)-farnesyl acetate), and phenylpropanoids ((E)-isoeugenol) [209]. [Table 6] summarizes the main constituents of the essential oils extracted from C. odorata blossoms at five stages of development (from green buds to overly mature flowers), showing qualitative and quantitative differences [209]. In all stages, geranyl acetate was present in the essential oil to the greatest extent, with the content being lowest in the earliest stage, stage 1 (18.57%) but highest in the second stage (27.08%). It was about the same in the third and fourth stages and slightly lower than in the second stage (25.85% and 25.42%) and was 26.5% in the fifth and final, overly mature stage. Other significant components in stage 1 were linalool (18.88%), benzyl benzoate (16.36%), (E,E)-α-farnesene (6.05%), and α-humulene (3.08%). In the second stage, linalool (20.5%), benzyl benzoate (13.92%), p-cresyl methyl ether (5.11%), α-humulene (3.08%), and methyl benzoate (2.85%) were also found. In the third, fourth, and fifth stages, the main components were very similar, consisting of linalool (25.69%, 25.92%, and 20.9%, respectively), benzyl benzoate (6.72%, 4.71%, and 5. 83%, respectively), p-cresyl methyl ether (6.48%, 8.29%, and 6.27%, respectively), methyl benzoate (4.31%, 5.5%, and 4.94%, respectively), and benzyl acetate (6.49%, 11.69%, and 14.84%, respectively). Interestingly, some components were present in the buds in much higher concentrations than in the mature flowers and vice versa. While benzyl acetate was present at 1.12% in the earliest stage and increased up to 14.84% in the overripe stage, the content of (E,E)-α-farnesene decreased from 6.05% in the earliest stage to 0.94% in the mature blossom stage. β-Caryophyllene was present only in the flowers at the earliest stage and was undetectable in the others. [Table 6] also lists the data from another investigation [218], which analyzed three different flower stages: small undeveloped green flowers, green flowers of intermediate maturity, and fully matured flowers of deep yellow coloration (equivalent to stages 2, 3, and 4 of reference [209]).

Table 6 Chemical composition of two C. odorata essential oils from three or five different flower maturity stages [209], [218].

Components	Reference	Stage 1 (%)	Stage 2 (%)	Stage 3 (%)	Stage 4 (%)	Stage 5 (%)
		green flower buds with closed petals	small green flowers with open petals	less mature green flowers turning yellow	mature yellow flowers	overly mature yellow flowers turning brown
In reference [209], five flower stages were studied, from buds to overripe flowers. In reference [218], three flower stages were investigated, from small still green flowers to mature yellow flowers. Values are given as relative percentages of compounds. Constituents were determined by GC-MS.
Geranyl acetate	[209]	18.57 ± 5.71	27.08 ± 1.87	25.85 ± 6.29	25.42 ± 4.86	26.5 ± 2
	[218]		0.87 ± 0.08	2.99 ± 0.38	1.96 ± 0.09
Linalool	[209]	18.88 ± 4.12	20.5 ± 3.04	25.69 ± 1.18	25.92 ± 2.11	20.9 ± 5.64
	[218]		20.95 ± 2.81	38.97 ± 4.27	35.49 ± 1.14
Tetradecane	[209]
	[218]		28.14 ± 1.21	12.25 ± 1.01	5.51 ± 0.65
Benzyl benzoate	[209]	16.36 ± 1.75	13.92 ± 1.47	6.72 ± 3.93	4.71 ± 2.45	5.83 ± 3.14
	[218]		4.72 ± 1.05	7.21 ± 2.17	6.19 ± 1.78
p-Cresyl methyl ether	[209]	2.27 ± 1.18	5.11 ± 0.5	6.48 ± 0.58	8.29 ± 1.93	6.27 ± 2.9
	[218]
(E,E)-α-Farnesene	[209]	6.05 ± 2.9	2.32 ± 1.85	2.41 ± 0.82	0.94 ± 0.71	1.16 ± 0.89
	[218]		1.47 ± 0.52	1.06 ± 0.58	2.34 ± 0.05
Methyl benzoate	[209]	0.87 ± 0.49	2.85 ± 0.12	4.31 ± 0.59	5.5 ± 1.07	4.94 ± 1.17
	[218]			3.20 ± 1.09	6.50 ± 1.42
(E)-Cinnamyl acetate	[209]		1.73 ± 1.43	2.85 ± 0.33	2.51 ± 1.07	4.06 ± 1.03
	[218]			1.42 ± 0.67	2.09 ± 0.39
α-Humulene	[209]	3.08 ± 4.81	3.65 ± 1.15	2.71 ± 2.71	2.28 ± 0.94	2.69 ± 1.39
	[218]		2.29 ± 0.43	1.25 ± 0.32	0.74 ± 0.11
Germacrene D	[209]	3.22 ± 1.83	1.65 ± 1.62	0.9 ± 0.74	0.07 ± 0.12	0.26 ± 0.16
	[218]		11.23 ± 1.47	7.06 ± 0.29	5.55 ± 0.17
τ-Cadinol	[209]	2.96 ± 1.64	0.59 ± 0.32	0.96 ± 0.61	0.34 ± 0.07	0.42 ± 0.19
	[218]
Farnesol	[209]	2.84 ± 0.63	1.16 ± 0.97	1.09 ± 0.66	0.32 ± 0.29	0.83 ± 0.5
	[218]		1.58 ± 0.39	1.19 ± 0.33	0.84 ± 0.04
Geraniol	[209]	2.24 ± 1.84	2.07 ± 1.76	2.97 ± 0.15	2.46 ± 1.19	1.93 ± 0.8
	[218]
τ-Muurolol	[209]	2.76 ± 1.35	0.84 ± 0.06	0.74 ± 0.61	0.19 ± 0.17	0.43 ± 0.2
	[218]		0.09 ± 0.01
Benzyl salicylate	[209]	1.51 ± 0.42	2.58 ± 0.81	1.66 ± 0.95	1.79 ± 1.22	2.38 ± 1.75
	[218]		0.48 ± 0.18	0.51 ± 0.13	1.37 ± 0.48
Benzyl acetate	[209]	1.12 ± 0.56	2.44 ± 0.28	6.49 ± 1.92	11.69 ± 0.61	14.84 ± 1.26
	[218]		0.15 ± 0.01	4.78 ± 1.25	11.63 ± 1.87
(E,E)-Farnesyl acetate	[209]	0.83 ± 0.46	0.44 ± 0.12	0.46 ± 0.31	0.22 ± 0.1	0.31 ± 0.23
	[218]		0.44 ± 1.19	0.28 ± 0.07	0.61 ± 0.30
(E)-iso-Eugenol	[209]	1.7 ± 2.94	2.42 ± 0.55	2.18 ± 0.72	1.89 ± 0.73	1.82 ± 0.64
	[218]		0.25 ± 0.03	1.03 ± 0.12	0.37 ± 0.08
α-Muurolene	[209]	0.78 ± 0.7	1.17 ± 2.03	0.25 ± 0.44
	[218]
α-Pinene	[209]	0.94 ± 0.58	0.6 ± 0.03	0.47 ± 0.09	0 ± 0.1	0.43 ± 0.04
	[218]		9.64 ± 0.95	2.85 ± 0.61	1.87 ± 0.32
β-Pinene	[209]	0.4 ± 0.25	0.35 ± 0.01	0.23 ± 0.19	0.33 ± 0.1	0.25 ± 0.08
	[218]		3.03 ± 0.22	0.90 ± 0.18	0.66 ± 0.11
γ-Cadinene	[209]	0.16 ± 0.28	0.26 ± 0.46		0.08 ± 0.14
	[218]				0.12 ± 0.01
β-Caryophyllene	[209]	1.04 ± 0.11
	[218]		5.46 ± 0.56	3.69 ± 0.45	1.69 ± 0.27

In another ylang-ylang oil, the main compounds were benzyl acetate (18.12%), linalool (15.23%), benzyl benzoate (11.39%), geranyl acetate (9.46%), methyl benzoate (7.64%), p-methyl anisole (7.38%), trans-caryophyllene (5.42%), germacrene D (4.61%), benzyl salicylate (4.47%), and α-farnesene (2.02%). Information on the blossom stage was not given [219]. However, the variable chemical composition of essential oils in the literature may depend on various factors cited above, in addition to the different stages of development of the harvested flowers [208], [209].

Four grades of ylang-ylang oil are available on the market from fresh, mature flowers with different qualities and uses: extra, first, second, and third [210], [220]. These are obtained by taking fractions at different time intervals during distillation, with physicochemical properties and fragrance varying by fraction [215]. The extra grade has the best fragrance because it is the first to be sampled and contains more volatile components responsible for the fragrance, such as linalool, p-cresyl methyl ether, methyl benzoate, benzyl acetate, and geranyl acetate. It is, therefore, used to produce high-quality perfumes [215], [220]. The later in time the fraction is taken, the more sesquiterpenes are contained, which are less volatile, such as β-caryophyllene, germacrene D, and (E,E)-α-farnesene [210], [215]. The first and second are used mainly in the cosmetics industry, and the third for soap production [210], [220]. There is also a fifth grade, complete, which is a mixture of all fractions [220].

Investigations on biological activity

Anti-inflammatory activity

Many properties of ylang-ylang essential oil have been studied, but few effects have been reported for the blossoms. Antibacterial, antifungal, and antiprotozoal effects of C. odorata have been investigated mainly from the essential oil of the whole plant [221]. Those effects are due to the presence of linalool, linalyl acetate, and methyl eugenol [210]. Insecticidal activity was detected primarily in ylang-ylang flower essential oils [222]. Furthermore, they displayed limited antioxidant actions [215] but significant anti-inflammatory potential [219].

An in vitro study demonstrated that ylang-ylang flower essential oil reduced leukocyte chemotaxis, which was induced by a chemoattractant that activated MAPK and phosphatidylinositol 3-kinase, releasing proinflammatory cytokines [219]. Since linalool already reduced LPS-induced production of TNF-α and IL-1β in vitro by inhibiting NFkB [49], it can be assumed that it is also responsible for hindering neutrophil chemotaxis by inhibiting the release of proinflammatory cytokines. However, the influence of other ylang-ylang oil components on the anti-inflammatory effect cannot be excluded. Excessive phagocytosis of neutrophils was also reduced, which could reduce associated tissue damage. In the in vivo experiments of the same study, ylang-ylang oil reduced paw edema and hyperalgesia in rats [219].

Psychological effects

Aromatherapists commonly use ylang-ylang oil through massage or inhalation due to its blood pressure and rapid breathing lowering effects, which is beneficial in trauma situations, and for its pleasant and relaxing scent [223], [224]. Furthermore, the essential oil showed antidepressant and euphoric properties [224]. A previous study reported that the exposure of male mice to ylang-ylang oil was shown to alter brain concentrations of two monoamine neurotransmitters associated with anxiety disorders. Dopamine concentration in the striatum decreased significantly, whereas serotonin content in the hippocampus increased. The components in the oil responsible for the anxiolytic effect were benzyl benzoate, benzyl alcohol, and linalool, which are believed to act synergistically [223]. Various studies have already demonstrated the anxiolytic effect of linalool [76], [225]. Other results suggested the influence of mitogen-activated protein kinase (MAPK) signaling pathways by exposure to ylang-ylang essential flower oil. Ylang-ylang oil down-regulated stress-triggered ERK1/2 phosphorylation, which usually causes phosphorylation from the cAMP response element-binding protein (CREB) in response to stress. Thereby, the expression of the c-Fos gene in the hippocampus and prefrontal cortex was decreased; thus, anxiety behavior in rats could be reduced [226].

There is a limited number of investigations concerning the insecticidal effect of ylang-ylang essential oil [227], [228], [229]. Applications studied on humans in clinical studies include local application [230], aromatherapy [231], and inhalation [232], [233]. It appears that clinical studies mainly focused on the impact of ylang-ylang essential oils against psychiatric disorders. In a randomized controlled trial, ylang-ylang aromatherapy was examined as an anxiety reliever in patients hospitalized for neuroradiological interventions. It reduced trait anxiety and salivary α-amylase activity, which was used as an anxiety biomarker [231]. Moreover, there are older studies with a small number of patients included, which indicated that ylang-ylang essential oil could increase calmness, reduce cognitive abilities [234], relax participants, and decrease blood pressure [232], [235], [236]. It can be concluded from these studies that ylang-ylang essential oil is likely to have pronounced calming and sedative effects [230], [231], [232], [234].

In vivo testing on mice showed neuropathic pain relief and decreased pain-associated anxiety [237]. Moreover, inhalation of ylang-ylang essential oil decreased anxiety and increased the social and cognitive abilities of autism-like rats [233]. Other studies suggested antiviral [238] and antifungal [239] effects of ylang-ylang essential oil. Finally, the possibility of application against insects, especially mosquitoes, should be mentioned [227], [228], [229].

Magnolia oil

Magnolia oil is the essential oil extracted by steam distillation from the blossoms of Michelia x alba (or Magnolia x alba), which belongs to the Magnoliaceae family. It is a popular scent compound in cosmetics and perfumes and has been used in Asian traditional medicine for centuries [240]. The genus Michelia includes about 30 species [241]. M. alba, a hybrid of Magnolia champaca and M. montana [240], also known as “white champaca” or “white jade orchid tree”, is native to tropical and subtropical Southeast Asia but is also very common in China and Taiwan as an ornamental plant [242], [243], [244]. Traditionally, the indigenous of Malaysia and Indonesia use the grey bark of the 10 – 30 m tall tree to treat fever, syphilis, gonorrhea, and malaria, and the blossoms as an abortifacient [240], [241]. Furthermore, the blossoms of M. alba are important for heart maintenance and as an antipyretic in Thailand [245]. Indian natives use them to prevent bronchitis, prostatitis, and leucorrhoea [246]. M. champaca, another species, is traditionally applied by Indian natives to treat abdominal tumors [243]. In addition, the flowers are used to make flower wreaths for wedding ceremonies in Indonesia, along with jasmine [244].

Cultivation of M. alba is difficult because the seeds germinate poorly due to the tough seed coat and are very short-lived [244]. The flowers are picked in the evening and at dawn, as they bloom between 10 p. m. and 9 a. m. [240]. They have a strong, fresh, sweet, and seductive fragrance [242], [247], [248]. They are used traditionally in China to aromatize green tea [248]. The species Michelia is popularly used to produce essential oils of high value for the perfume industry. It is, for example, the main note in Diorʼs Jʼadore. The essential oil of M. alba is very expensive for perfume production due to its low yield [242]. The fragrance of the blossom essential oil can be characterized as sugary, floral, and champagne-like with a little herbal flavor [240].

Chemical composition

The chemical composition of M. alba flower essential oil was reported to include monoterpenes (3-carene, α-, β-pinene, β-myrcene, and camphene), monoterpene alcohols (linalool, α-terpineol, nerol, terpinen-4-ol, and endo-borneol), sesquiterpenes (β-elemene ([Fig. 1 x]), caryophyllene, β-selinene, γ-, δ-cadinene, 1,5,9,9-tetramethyl-1,4,7-cycloundecatriene ([Fig. 1 y]), copaene, α-cubebene, α-santalene, cis-α-bergamotene, and β-farnesene), sesquiterpene alcohols (τ-Muurolol, nerolidol, cubenol, neointermedeol, spathulenol ([Fig. 1 z]), and α-cadinol), sesquiterpene oxides (caryophyllene oxide), phenylpropanoids (methyl isoeugenol and safrole), carbonic acid esters (methyl 2-methylbutyrate, methylethylacetic acid, ethyl 2-methylbutyrate, linoleic acid ethyl ester, 9,12-Octadecadienoic acid (Z,Z)-, and methyl ester), and alcohols (phenylethyl alcohol). Other constituents were detected in traces under 0.1% [249]. The components are summarized in [Table 7]. The major compound of M. alba flower essential oil extracted by steam distillation was linalool (43.47%), followed by β-elemene (8.03%), caryophyllene (6.80%), methyl 2-methylbutyrate (4.05%), β-selinene (4.00%), methyl isoeugenol (3.30%), and δ-cadinene (3.30%) [249]. The main compounds identified in other studies were partly very different. The analysis of M. alba flower essential oil resulted in a much higher percentage of linalool (91.74%), followed by ethyl 2-methylbutyrate (1.47%), β-elemene (1.42%), methyl eugenol (1.36%), methyl 2-methylbutyrate (1.31%), β- caryophyllene (1.00%), germacrene D (0.82%), β-selinene (0.59%), and α-humulene (0.30%) as the central essential oil components of M. alba extracted by steam distillation ([Table 7]) [247]. For another study, a magnolia oil with the main compounds linalool (66.9%), caryophyllene (7.5%), and β-elemene (5.2%) was used ([Table 7]) [250].

Table 7 Chemical composition of three M. alba flower essential oils [247], [249], [250].

Compounds	% [249]	% [247]	% [250]
Values are given as relative percentages of compounds. The constituents were determined by GC-MS.
Linalool	43.47	91.74	66.93
β-Elemene	8.03	1.42	5.18
Caryophyllene	6.80		7.56
Methyl 2-methylbutyrate	4.05	1.31
β-Selinene	4.00	0.59	1.80
α-Selinene			1.55
Methyl isoeugenol	3.30
δ-Cadinene	3.30
β-cis-Ocimene	2.94		1.12
3-Carene	2.84
1,5,9,9-Tetramethyl-1,4,7-cycloundecatriene	1.71
Copaene	1.40		1.08
α-Terpineol	1.29
τ-Muurolol	0.93
Nerolidol	0.74
Caryophyllene oxide	0.70		1.30
Phenylethyl alcohol	0.69
Nerol	0.56
Cubenol	0.53
Neointermedeol	0.52
β-Pinene	0.48
Ethyl 2-methylbutyrate	0.36
α-Cubebene	0.34		0.29
Spathulenol	0.28
α-Cadinol	0.27
Linoleic acid ethyl ester	0.25
(Z)-9-Cycloheptadecen-1-one	0.24
α-Pinene	0.24
α-Santalene	0.23
(Z,Z)-9,12-Octadecadienoic acid, methyl ester	0.22
γ-Cadinene	0.21
cis-α-Bergamotene	0.21		0.25
Linalool oxide acetate	0.20
β-Farnesene	0.20
Terpinen-4-ol	0.20
endo-Borneol	0.18
β-Mycrene	0.12
(−)-Camphene	0.11
Safrole	0.10
Indole	0.09
α-Humulene		0.30	2.16
Germecrene D		0.82	1.30

Various methods can produce the essential oil from M. alba blossoms, but yields and compositions of the products vary. Water distillation yielded 0.23% essential oil and water-steam and steam distillation 0.12%, respectively. Linalool (83 – 91%) was the primary component of all three distillation methods. Cold enfleurage absolute yielded 0.35% with indole as the major compound (67.9%). Hot enfleurage produced 2.75%, mainly comprising linalool (91%). The yield of hexane absolute was 0.05%, dominated by phenylethyl alcohol (39.1%) and indole (25.98%). The essential oil of the distillation processes was deep yellow in color and had a smell of boiled flowers. The absolute prepared by enfleurage had the most similar scent to fresh blossoms due to the indole content, which can boost the perceived odor strength and enhance the stability of other fragrant substances in essential oils [247].

Investigations on biological activity

Antimicrobial activity

A study showed that the essential oil of M. alba flowers in the vapor phase inhibited the growth of Aspergillus flavus on malt extract agar by 100%. Furthermore, the oil vapor exhibited antifungal properties in cooked brown rice, which is easily contaminated with bacteria or mold, and could extend the shelf-life by a factor of six [249], [250]. Linalool, the main component in the essential oil, interrupted the cell wall biosynthesis and enhanced the ionic permeability of the mold cell membrane, thus destroying it [251]. However, only 11.32% linalool of 43.47% in the essential oil remained after cooking the brown rice. In contrast, β-elemene content increased from 8.03% to 34.38% and caryophyllene from 8.80% to 19.58% by cooking the rice. In addition, treatment of brown rice with the essential oil vapor of M. alba flowers enhanced odor, taste, color, and overall consumer acceptance of brown rice [249]. The scent of linalool was defined as floral, sweet, and citrusy, while β-elemene smelled grassy and woody, and caryophyllene smelled like bubble gum [252]. Cooking duration and hardness of cooked rice, furthermore, were reduced by harming the rice bran layer, thereby promoting water absorption. No adverse effects were shown on its nutritive composition. Additionally, the study showed that consumption of oil-treated brown rice could stimulate the human brain to increase alpha and beta waves during smelling, chewing, and swallowing, which had stress-reducing and relaxing effects [249].

Full inhibition of spore germination and mycelial growth of A. flavus by M. alba in the vapor phase (≥ 450 µL/L air) was demonstrated [253]. However, the essential oil from the leaves of M. alba was more effective against A. flavus than the flower essential oil [249]. Furthermore, an inhibitory effect of M. alba essential flower oil was reported on E. coli and S. aureus growth by 63.10% [254].

Other activity

The essential oil of the flowers of M. alba showed an antidepressant effect in animal experiments on mice, which, however, was weaker than that of L. angustifolia. The antidepressant effect was believed to be due to the presence of linalool and phenylethyl alcohol [255]. Many studies have already investigated the antidepressant-like effects of linalool. Results indicated that linalool acts via the monoaminergic system, through the serotonergic pathway via postsynaptic 5-HT_1A receptors and the adrenergic system via α ₂-receptors [256]. Another study demonstrated an antidepressant effect of phenylethyl alcohol in mice [257].

Furthermore, the antidiabetic activities of M. alba flower essential oil were studied. The essential oil exerted promising α-amylase inhibitory activity, which could reduce postprandial hyperglycemia and, thus, have a positive effect on insulin secretion and/or insulin action in diabetic patients. After the essential oil showed a considerable inhibitory effect on the carbohydrate-hydrolyzing enzyme in the α-amylase inhibition assay, an in silico study of the five main compounds linalool, eugenol methyl ether, indole, linalool oxide, and pyran linalool oxide was performed. Linalool was found to be the compound with the highest docking interaction. However, in vivo experiments and clinical studies are still required [245].

Biological activity of main components

Although the flowers of M. alba are popular in traditional Asian medicine [240], comparatively few studies have been conducted on the biological effects of the essential oil of the blossoms and their use in aromatherapy. The main component of the essential oil is linalool, which has already been found in a wide variety of concentrations up to 74% [242]. Young flowers of M. alba contained an exceptionally high content of linalool, which is 10 times higher compared to leaves and stems [258]. The extensive biological activity of linalool has already been cited above.

In Asia, there are many reports about the potential role of β-elemene in cancer therapy, another major component of M. alba essential oil (8.06%, [Table 7]) [249]. In traditional Chinese medicine (TCM), it is already used to treat a wide variety of cancers [259].

The bicyclic sesquiterpene and third prominent constituent of M. alba essential oil, caryophyllene (6.80%, [Table 7]), also showed many biological properties as a selective phytocannabinoid agonist of type 2 receptors (CB2-R) [260]. Various effects of this component have been reported, such as anxiolytic [261], antidepressant [261], analgesic [262], anticonvulsant [263], and neuroprotective [264] properties in vivo, as well as anti-inflammatory [265] and antioxidant [266] activities in vitro.

Thus, due to high linalool, β-elemene, and caryophyllene contents, all above described properties could also be expected from the flower essential oil of M. alba. However, much research is still needed on this topic.

Discussion and Conclusion

This overview focuses on essential oils derived from seven aromatic blossoms selected for their popular use in aromatherapy, summarizing their most important chemical constituents, biological activities, and potential clinical applications. The medicinal value of various essential oils was already recognized thousands of years ago, mainly in ancient Egypt, Mesopotamia, China, Persia, and India [267]. Most of the mentioned blossoms originally derived from exotic plants from Asia: damask rose from Iran, Spanish jasmine from India (and Africa), bitter orange and white champaca from Southeast Asia, ylang-ylang from Indonesia, and German chamomile from West Asia (and Europe). True lavender is native to the Mediterranean region of Europe. However, yields of the essential oil flowers described are rather low: L. angustifolia flowers contain 2.0 – 3.0% of essential oil [38], C. odorata blossoms 1.0 – 2.0% [217], M. recutita flowers 0.24 – 2.0% [91], M. alba blossoms 0.119 – 0.225% [247], C. aurantium flowers 0.08 – 0.13% [188], J. grandiflorum flowers 0.05% [165], and R. damascena petals 0.03 – 0.04% [132], making some of them the most expensive essential oils (rose, jasmine, and neroli oil). A complex mixture of more than 100 different low-molecular-weight compounds is usually found in essential oils from blossoms in widely varying concentrations. These compounds mostly belong to the monoterpenes and sesquiterpenes, but phenylpropanoids also occur. Interestingly, most of the compounds are present in low concentrations (between 0.1 – 8.0%), and only a few significant constituents can account for up to 70% of the total oil [4]. These mainly determine the biological properties of the oil. However, synergistic effects are often emphasized, which can also be initiated by substances present in small quantities in the essential oil [38], [50]. It is worth mentioning that steam distillation is not suitable for the extraction of all flowers. Especially when extracting jasmine blossoms, this method negatively affects the oilʼs composition and fragrance. Thus, the jasmine essential oil has barely any commercial value, unlike the absolute [168].

Although each essential flower oil described in this work has its characteristics in terms of origin, harvest, yield, chemical composition, fragrance, and appearance, some commonalities were found in the application areas and partly in the oil components. However, the reported chemical compositions of individual essential oils strongly vary. The variation is primarily due to ecological factors such as geographical origin, climate, and soil, as well as genotype, developmental stages of the blossoms at the time of harvest, extraction methods, storage conditions, and the method of analysis [3], [133], [145]. There will undoubtedly be some challenges in the future to produce essential oils of constant composition and quality and, thus, ensure constant pharmacological effects. Therefore, standardization of essential oils, production procedures, and aromatic plant cultivation is required and should be a topic in further studies.

Considerable preclinical studies have documented medicinal properties and mechanisms of action of essential oils from blossoms. Many studies have highlighted much attention on the antimicrobial activities of essential oils, especially from L. angustifolia flowers. The essential oil constituents and their antimicrobial activity vary depending on the harvest origin since plants often secrete essential oils as a protection against corresponding environmental influences and as a defense against microbes [51]. However, the large number of ingredients in essential oils results in a great variety of mechanisms of action and molecular targets [4]. For example, linalool, one of the main components of lavender oil, kills bacterial cells by damaging the integrity of the bacterial cell membrane by reducing the membrane potential. Furthermore, linalool affects metabolites and key enzymes of diverse metabolic pathways [54], [55] and is effective against multi-resistant bacteria such as E. coli and P. aeruginosa [44]. It is found not only in L. angustifolia but also in comparable concentrations in C. aurantium, C. odorata, and M. alba and in lower concentrations in J. grandiflorum. In M. recutita and R. damascene, linalool is present in very low concentrations (below 1%). Geraniol, geranyl acetate, eugenol, and nerol from damask rose oil [147], as well as β-pinene, β-myrcene, limonene, and α-terpineol from neroli oil [185], also showed antimicrobial activities in previous studies. Jasmine [178] was found to show lower antimicrobial potential. Essential oils from blossoms have been demonstrated to be beneficial antimicrobial agents in the food and pharmaceutical industries. Since essential oils consist of several components that attack pathogens by different mechanisms of action, the problem of antibiotic resistance due to multi-drug resistant pathogens, as well as the negative impact on local ecosystems when antibiotics enter surface waters and soils, could be counteracted in the future by using essential oils to support antibiotic therapy [44]. Hospital stays, morbidity, and mortality could be reduced. In addition, it has been noted that lavender essential oil or linalool could be used as a preservative in food, for example, by spraying it into the headspace of packaging or applying it to coatings [57]. Moreover, essential oils of flowers such as ylang-ylang or jasmine proved to be effective, environmentally friendly insect repellents and insecticides [178], [228].

Further preclinical studies have demonstrated anti-inflammatory [49], antioxidant [51], and anticancer [115] effects of flower essential oils in vitro, as well as sedative [71], anti-anxiety [186], anti-stress [226], antidepressant [255], analgesic, and antispasmodic [193] effects in animal models. Clinical studies confirm the effectiveness of essential flower oils for specific issues. They are mainly used for psychiatric disorders. Lavender and chamomile oil were reported to show effects against stress, anxiety, depression, and sleep disorders [67], [119]. They are thought to act (among other effects) through the limbic system, where they may enhance the action of GABA in the amygdala [18], [118], [119]. Damask rose oil, neroli oil, and ylang-ylang oil have also shown anti-anxiety, antidepressant, and anti-stress effects in various clinical studies [137], [200], [231]. In addition, essential flower oils have proven to be effective supplements in somatic diseases and exceptional situations through aromatherapy [82], [85]. The most common forms of application are inhalation [142], [143], oral intake [140], [141], and topical application [144]. However, only a few studies have been conducted in humans, with lavender oil being the most clinically studied compared to the other flower oils chosen. No clinical studies using magnolia flower essential oil could be found in the databases, although it is popular in traditional Asian medicine, and antidepressant effects have already been shown in animal models [255]. Anxiety and depression are mental disorders that represent significant and, especially since the COVID-19 pandemic, dramatically growing public health problems. According to the World Health Organisation, more than 300 million people suffer from major depressive disorder, and depression is one of the most common mental disorders [268]. However, antidepressant drugs only take effect after a few weeks and have numerous side effects, which impair patient compliance. Essential oils could be administered as a supportive treatment with lower toxicity, as the components can penetrate the blood–brain barrier and act on receptors associated with depression [269]. However, the lack of human studies limits the potential of using essential oils as effective and safe phytotherapeutics.

Since our overview is not a systematic review, some weaknesses have to be considered: essential oils were chosen by the authors for being, in our opinion, the most important flower essential oils used in aromatherapy. We therefore neither discussed all blossom oils nor did we include all possible biological impacts of these oils. The literature was cited due to its availability from the databases, using no systematic search methods. The literature excluded was mainly due to language (only English and German literature was considered), unavailability, poor scientific methodology, and low outcome.

In conclusion, essential flower oils can make a significant contribution to the healing of various diseases. Therefore, they should be further explored in well-designed clinical trials to achieve a high level of scientific evidence and fully identify mechanisms of action and possible adverse effects in humans.

Contributorsʼ Statement

Conceptualization, S. P. and I. S.; writing–original draft preparation, S. P.; writing–review and editing, I. S.; supervision, I. S. All authors have read and agreed to the published version of the manuscript.

Conflict of Interest

The authors declare no conflicts of interest.

Acknowledgements

This work is dedicated to Professors Rudolf Bauer, Chlodwig Franz, Brigitte Kopp, and Hermann Stuppner for their invaluable contributions and commitment to Austrian pharmacognosy, as well as to Prof. Gerhard Buchbauer for his efforts in essential oil research.

^# This work is dedicated to Professors Rudolf Bauer, Chlodwig Franz, Brigitte Kopp, and Hermann Stuppner for their invaluable contributions and commitment to Austrian Pharmacognosy.

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Publication History

Received: 28 September 2023

Accepted after revision: 03 November 2023

Article published online:
06 June 2024