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Biological properties and resistance reversal effect of Helichrysum
italicum (Roth) G. Don
E. Guinoiseau1, V. Lorenzi1,*, A. Luciani1, A. Muselli2, J. Costa2, J. Casanova3 and L. Berti1
1
Université de Corse, UMR CNRS 6134, Laboratoire Biochimie et Biologie Moléculaire du Végétal, Campus Grimaldi,
BP 52, 20250 Corte, France
2
Université de Corse, UMR CNRS 6134, Laboratoire Chimie des Produits Naturels, Campus Grimaldi, BP 52, 20250
Corte, France
3
Université de Corse, UMR CNRS 6134, Laboratoire de Chimie et Biomasse, Route des Sanguinaires, 20000 Ajaccio,
France
*E-mail address of corresponding author: vlorenzi@univ-corse.fr
Helichrysum italicum, which belongs to the family Asteraceae, is an evergreen plant native to the Mediterranean area.
Since older times, extracts and essential oils (EOs) from the aerial parts (leaves, flowering tops) of the plant are used in
traditional medicine for herbal remedies. They are known to possess several biological properties, including antimicrobial,
anti-inflammatory, antioxidant and anti-viral activities, as well as preventive effects against insects. The chemical
variability exhibited by H. italicum extracts and EOs could explain all these health promoting activities. This review
summaries the present state of knowledge on chemical constituents of H. italicum and its biological properties.
Keywords Helichrysum italicum sp; biological activities; chemical constituents; essential oils; extracts.
1. Introduction
The genus Helichrysum (Miller) belongs to the Asteraceae family and is a very large genus including approximately
600 species widespread all over the world. Helichrysum species are distributed from the lower-meso-Mediterranean to
the lower-sub-humid bioclimatic environments, growing at a wide range of altitudes from the sea level up to 1700 m,
preferably on sandy or loamy soils [1]. Almost 25 species are native of Mediterranean area and the most widespread
species is Helichrysum italicum (Roth) G. Don (syn. H. augustifolium DC). It is a small aromatic shrub, up to 40-50 cm
high, with yellow flowers growing on dry cliffs and sandy soil (Figure 1).
Fig. 1 photography of the yellow flowering tops of the plant.
H. italicum subsp. italicum and H. italicum subsp. microphyllum (Willd.) Nyman are the most investigated
subspecies [2].
H. italicum has some fairly unusual and very useful properties. In Europe, the plant is used over the years to refresh
the air, repel insects and for medicinal purposes [3]. For instance, dried inflorescences of this plant are used as a moth
antifeedant whereas flowering tops find application in folk medicine for their anti-inflammatory and anti-allergic
properties and in cosmetics for treatment of skin sunburn and erythema [4-5]. Decoctions of flowering tops are also
used for fumigations in the treatment of asthma [6].
Besides its ornamental value, the success of this plant is also due to several activities related to the essential oils
(EOs) produced by the glandular hairs present on their leaves and flower heads. Only the EO extracted from the plants
belonging to H. italicum species is used in aromatherapy practice. Its cicatrizant properties suggest that the EO can be
used to aid skin regeneration and help with wound healing. Voinchet and Giraud-Robert [7] investigated the therapeutic
effects and potential clinical applications of H. italicum EO and a macerated oil of musk rose (Rosa rubiginosa) after
cosmetic and reconstructive surgery. The objectives of reducing inflammation, oedema and bruising were well
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achieved. The authors highlighted that neryl acetate, a main component of the EO, contributed to pain relief. -They also
attributed the observed effects to the occurrence of italidiones in H. italicum EO. This class of molecules is also reputed
to have anti-haematomal properties so that H. italicum EO is often called the ‘super arnica of aromatherapy’. That is
why this useful phlebotonic is indicated for couperose skin (red veins), haematoma (even old haematomas), thrombosis
and the prevention of bruises [8]. When H. italicum EO is mixed with some other specific EOs, the mixtures are thought
to be anti-allergenic. So, these aromatherapy prescriptions could be helpful in cases of asthma, hay fever or eczema
(Table 1).
Table 1 H. italicum essential oil in aromatherapy prescriptions
System H. italicum in mixture with
Integumentary (eczema, inflammation, wound
healing)
Trauma
Lavender, Roman chamomile, geranium, yarrow, vetiver,
patchouli, sandalwood, cypress, rose
Can be used neat or diluted (10-50%)
Immune (allergic responses) Rose, sandalwood, German chamomile
Due to its skin regenerative properties, H. italicum EO is known to prevent skin aging. That is why it is widely used
in the formulation of anti-aging creams and cosmetics based on H. italicum EO that are now flooding the market.
The EO of H. italicum is obtained by steam distillation of flowering tops. The flowering tops are cut by hand, in wild
places, and the cut is from mid-June to mid-July, early flowering. The flowering tops are processed after harvesting.
The yield of production is about 0.9 to 1.5: ie a ton of flowering tops produces about 900 g to 1.5 kg of EO. This EO is
increasingly sought after, but unfortunately many sites are endangered (fires, advanced buildings...) and its price
becomes higher due to its rarity.
2. Components of H. Italicum Extracts and Essential Oils
Since the end of the fifties, phytochemicals belonging to different families of compounds have been identified in
solvent extracts of H. italicum and when necessary their structure elucidated. Representative components are listed
below:
- acids: acetic acid, caprilic acid [9], fatty acids [10];
- angeloylated glycerides, constituting an unusual class of lipids named santinols [11];
- phenolic compounds: caffeic, p-coumaric, ferulic and chlorogenic acids [9, 12] as well as phenolics that includes
coumarates, benzofurans, pyrones [11] and 7-hydroxy-5-methoxyphthalide and 12-hydroxytremetone (bitalin A) [12];
- triterpenes: β- sitosterol and ursolic acid [10], α-amyrin, uvaol and ursolic acid lactone [13]
- flavonoids : apigenin, glycosyl-apigenin, luteolin, gnafalin, naringenin, glycosyl-naringenin [4], kaempferol-3-
glucoside and naringenin-glycoside [5], B-ring deoxyflavonoids [14];
- chalcones: glycosyl-chalcone [4] 4,2',4',6'-tetrahydroxychalcone-2'-glucoside [14];
- acetophenone glucosides and a benzo-γ-pyrone glucoside [15];
- arzanol, a prenylated heterodimeric phloroglucinyl α-pyrone and helipyrone, a dimeric pyrone [15,16,17].
Identification of individual components of H. italicum EO has been investigated since a long time. However, our
attention will be focused on papers that report on chemical analyses carried out with modern analytical techniques. H.
italicum EO exhibited various compositions depending of the sub-species, the location of harvest, the physiological
stage of the plant, etc. They are summarized on the table 2.
In short, H. italicum EOs contained numerous monoterpenes and sesquiterpenes usually found in EOs. The structure
of new compounds has been elucidated, various acyclic 1,3-diones [18, 19], italicene and isoitalicene, helifolene and
iso-helifolene, various bisabolane diols [32] eudesm-5-en-11-ol [20].
H. italicum of the Adriatic coast (sub-species not specified) produces EO with α-pinene, α- and γ-curcumene as
major components [33, 34, 35]. EO (subsp italicum) from Tuscany contained mainly α-pinene and neryl acetate [25]
while an oil sample from Southern Italy was dominated by iso-italicene epoxide [26]. Other Italian EOs contained
mainly γ-curcumene, β-selinene and α-selinene [27].
H. italicum EOs from Mediterranean islands exhibited various compositions. For instance, oil from the Greek island
of Amorgos (ssp italicum) was dominated by geraniol [28] while plants from Crete (ssp microphyllum) produced oil
containing mainly sequiterpene hydrocarbons [21]. H. italicum ssp microphyllum from Corsica and Sardinia is rich in
neryl acetate [1, 22, 23] while some samples contained appreciable amounts of eudesm-5-en-11-ol [24]. Some Sardinian
oil samples contained rosifoliol and γ-curcumene as main components [22].
The composition of H. italicum ssp italicum EO from Corsica and Tuscan Archipelago Islands was dominated by
neryl acetate [25, 29, 30]. Correlations between the EO composition and various parameters were shown: texture and
acidity of soils, inorganic composition of plant and soil, vegetative stage of development [37]. Some oil samples from
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Tuscan Archipelago Islands contained unusually high amounts of β-diketones [30]. Oils from Elba Island (Italy) were
characterized by a high content of oxygenated monoterpenes while monoterpene hydrocarbons and sesquiterpene
hydrocarbons reached appreciable in some samples [31, 35, 36].
Table 2 Components of H. italicum essential oils.
origin Major components Other components Ref
Helichrysum italicum ssp microphyllum
Crete
β
-selinene (17.1/16.7%),
γ-curcumene (13.7/6.6%)
α-selinene (3.8/5.4%),
Italicene (5.1/1.4%). [21]
Sardinia
neryl acetate (28.9%),
neryl propionate (11.4%)
γ
-curcumene (11.4%),
nerol (10.7%) [22]
Sardinia rosifoliol (20.2%),
γ-curcumene (18.2%) linalool (14.9%) [22]
Sardinia neryl acetate (21.4/16.9%),
dihydro-occidentalol (12.2/7.6%)
nerol (7.3/5.4%),
neryl propionate (5.6/4.6%) [23]
Sardinia neryl acetate (17.6-56.1%), eudesmen-
5-en-11-ol (3.7-23.5%) nerol (3.7-14.4%) [24]
Corsica neryl acetate (55.7/41.5%) neryl propionate (12.7/5.6%) [1]
Helichrysum italicum ssp italicum
Tuscany
(Italy) α-pinene (4.1-53.5%),
neryl acetate (0.3-22.0%)
β
-selinene (7.2-12.5%),
β-caryophyllene (5.7-11.0%) [25]
Cilento
(Italy) iso-italicene epoxide (16.8%) hexadecene (9.8%),
β-costol (7.5%) [26]
Italy
γ
-curcumene (0-41.0%),
β-selinene (0-38.0%),
α-selinene (0-26.5%),
γ-eudesmol (0-20.4%)
nerol (0.4-18.8%),
(E)-β-caryophyllene (0-18.6%),
neryl acetate (0.4-15.1%)
[27]
Amorgos
(Greece) geraniol (35.6%) geranyl acetate (14.7 %),
(E)-nerolidol (11.9%). [28]
Corsica
neryl acetate (15.8-42.5%)
γ-curcumene (0.8-13.6%)
limonene (1.9-7.3%),
neryl propionate (1.5-6.7%),
[29]
[25]
Corsica
neryl acetate (32.0%),
ar-curcumene (6.4%)
4,6,9-trimethyldec-8-en-3,5-dione (11.0%) [27]
Tuscan
Archipelago
(Italy)
neryl acetate (14.9–44.5%),
neryl propionate (3.0–16.4%)
γ-curcumene (5.4-13.7%),
nerol (1.4-7.6%),
eudesm-5-en-11-ol (1.1-7.6%)
[30]
Elba Island
(Italy)
neryl acetate (5.6-45.9%),
α-pinene (0.8 –32.9%),
1,8-cineole (up to 18.2%)
eudesm-5-en-11-ol (1.8-17.2%),
nerol (up to 12.8%),
limonene (up to 12.9%)
[31]
Elba Island
(Italy)
neryl acetate (11.4%),
γ−eudesmol (8.5%)
(Ε)−
β
−caryophyllene (7.8%),
γ-curcumene (7.7%) [27]
Sub-species not specified
Ex-Yugoslavia α-pinene (21.7%),
γ-curcumene (10.4%)
neryl acetate (6.1%),
β-selinene (6.0%), [32]
Croatian Adriatic
coast α-pinene (0.1-29.9%),
α-curcumene (1.0-28.6%),
γ-curcumene (0-22.0%)
α-cedrene (0.2-16.7%),
neryl acetate (4.1-13.5%),
spathulenol (up to 13.2%)
[33]
Croatia α-pinene (10.2%),
neryl acetate (11.5%) α-cedrene (9.6%) [34]
Elba island
(Italy)
neryl acetate (25.3% ± 2.9),
α-pinene (14.5% ± 2.1)
limonene (12.3% ± 2.8),
γ-curcumene (8.7% ± 1.4).
[35]
[36]
It is likely that the variability of components present in H. italicum extracts and EOs has a strong influence on their
biological activity.
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3. Biological Activities of H. Italicum Essential Oil and Extracts
Metabolites isolated from H. italicum, and especially its volatile fraction, have been found to display many biological
properties, such as antimicrobial, anti-inflammatory, anti-viral antioxidant activities. The insecticidal effects of the EO
have also been described. Until now, no reports on the possible phytotoxic activity of the secondary metabolites of the
plant have been reported.
3.1. Antimicrobial activity
Of all the properties claimed for H. italicum, the antibacterial effect of extracts, EOs and their constituents has received
a main attention. Several data report the effectiveness of H. italicum extracts against Gram positive bacteria. Nostro and
coworkers [38] demonstrated that diethyl ether extracts of H. italicum has inhibitory effect on Staphylococcus aureus
strains reducing both their growth and some of the enzymes considered as virulence factors. With minimum inhibitory
concentration (MIC) values ranging from 125 to 500 mg/L, this extract is so effective on methicillin sensitive S. aureus
strains (MSSA) as on methicillin resistant S. aureus isolates (MRSA). It also inhibits the enzymatic activity of these
strains with a more pronounced effect on the coagulase than on the DNAse, lipase and thermonuclease. Other works
have been done to evaluate the effects of H. italicum extracts on different bacterial virulence factors, such as toxins
production or cell aggregation. It has been shown that low concentrations of H. italicum diethyl ether extract reduce the
enterotoxins B and C production by S. aureus [39]. In the same way, it was highlighted that subminimum inhibitory
concentrations (7.81 to 31.25 µg/mL) of H. italicum ethanolic extracts inhibit in vitro adherence and cellular
aggregation of the cariogenic Streptococcus mutans bacterium [40] extracts seem to be able to interfere with bacterial
virulence and thereby show considerable interest to control undesirable and pathogenic bacteria.
Two main studies carried out in our laboratories report the antibacterial properties of H. italicum EO and its related
constituents. Rossi and coworkers [41] demonstrated that the EO, obtained from endemic plants of Corsica, is more
effective on the Gram positive bacterium S. aureus than on the Gram negative strains Escherichia coli, Enterobacter
aerogenes, Pseudomonas aeruginosa. It is commonly known that Gram negative bacteria are less susceptible to EOs
than Gram positive bacteria, and this is directly connected to the bacterial cell wall structure. In Gram negative bacteria,
the cell wall is a complex envelope constituted by the cytoplasmic membrane, the periplasm and the outer membrane.
The latter one restricts diffusion of hydrophobic molecules through its lipopolysaccharide covering, thus acting as a
strong permeability barrier [42].
So, these bacteria are particularly difficult to eradicate, especially as they have also developed effective mechanisms
of resistance such as efflux pumps overexpression. Efflux pumps play a key role in the bacterial resistance to antibiotics
and contribute to the spread of multidrug resistant pathogens (MDR phenotype). These protein carriers are able to expel
from the cells structurally diverse drugs, including antibiotics, rendering them therapeutically ineffective. By blocking
this mechanism with efflux pump inhibitors (EPIs), it is possible to restore the effectiveness of antibiotics. Lorenzi and
coworkers [43] have shown that H. italicum EO significantly reduces the MDR resistance of several Gram negative
strains of Enterobacter aerogenes, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. The
highest activity was obtained for the MDR clinical isolate of E. aerogenes EA27, which overexpresses the AcrAB-TolC
efflux pump and are thus resistant against the last resort antibiotic used in intensive care units, i.e chloramphenicol. At a
concentration of 2.5%, H. italicum EO reduces eightfold the MIC (from 1,024 to 128 mg/L) of chloramphenicol for
EA27 strain. Moreover, H. italicum EO restores the chloramphenicol susceptibility of EA27 to a level that is close to
that of the control phenylalanine arginine ß-naphthylamide (PAßN), i.e MIC of 64 mg/mL. It is clear from these data
that H. italicum EO contains one or more compounds that have EPI activity. Therefore, a chromatographic fractionation
assay was made to isolate that or these agents. Then, the EPI’s activity of the main fractions recovered was evaluated
against the derivative mutant of E. aerogenes EA27, i.e EAEP289 strain. It has been shown that combinations of the
two most active fractions (italidiones, F2 and alcohols, F3) can reduce chloramphenicol resistance from an initial MIC
of 1,024 to 128 mg/L. Reduction of resistance was also achieved when either the F2 or F3 fraction was combined with
PAßN. Combination of the latter produced the strongest effect comparable to a complete reversal of chloramphenicol
resistance (MIC of less than 0.25 mg/L). Due to the high activity of the F3 fraction, several chloramphenicol
susceptibility assays were performed with commercially available constituents of this fraction. Among the compounds
tested, geraniol produces significant restoration of susceptibility of the MDR strain EAEP289 to chloramphenicol by as
much as 16-fold. When combined with PAßN, it rendered the bacterium fully susceptible to chloramphenicol, i.e., it
completely reversed initial resistance. Geraniol (3,7-dimethylocta-2(E),6-dien-1-ol) is an acyclic monoterpenic
compound which presents a stereochemistry (E). Its hydrocarbon backbone is constituted of two isoprene units and
functionalized with an hydroxyl group (Figure 2).
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OH
Fig. 2 Chemical structure of geraniol
Geraniol is soluble in dimethylsulfoxide (DMSO) and methanol. These solvents complicate experiments and cause reproducibility
difficulties, related to the lack of homogeneity of the solutions. So, complementary tests were carried out with several derivatives
compounds of geraniol in order to improve its solubility while retaining its efficiency. It was found that hydrochloride geranyl amine
salt (Figure 3), a water soluble compound, is as effective as geraniol since it reduces the MIC of chloramphenicol to the same extent
as PAßN.
NH3+Cl-
Fig. 3 Chemical structure of hydrochloride geranyl amine
It was thus concluded that the replacement of the primary alcohol group of geraniol by an amino-hydrochloride
function has improved the solubility of the molecule.
If the antibacterial properties of H. italicum are widely described in the literature, less is known about its effect
against yeasts and fungi. However, it has been reported that the EO of H. italicum from Croatia and, more precisely, its
oxygenated fraction are active against Candida albicans. The terpenoid components of this fraction inhibit the growth
of the yeast by producing an inhibition zone of 10 mm and a MIC of 5 µg/mL [37].
3.2. Anti-inflammatory activity
H. italicum is known to contain ketones that contribute to reduce the inflammation process. Arzanol, a prenylated
heterodimeric phloroglucinyl α-pyrone (Figure 4), was identified as the major anti-inflammatory component [44].
OH
HO OH
O
O
OH
O
Fig. 4 Chemical structure of arzanol
Inflammation is a complex biological response that involves several enzymatic reactions. The prostanoids and
leukotrienes (LTs) formed from arachidonic acid via the cyclooxygenase (COX)-1/2 and 5-lipoxygenase (5-LO)
pathway, respectively mediate inflammation, chronic tissue modeling, cancer, asthma and autoimmune disorders. The
non-steroidal anti-inflammatory drugs administered for therapeutic purposes act by blocking formation of all the
prostanoids but their clinical use is hampered by severe side effects including gastrointestinal injuries, renal irritations
and cardiovascular risks [19]. It has been shown that arzanol potently inhibits the nuclear transcription factor NFκβ
activation in T cells as well as the release of pro-inflammatory mediators such as interleukin (IL)-1β, Il-6, Il-8, tumor
necrosis factor (TNF)α and in lipopolysaccharide stimulated monocytes [18]. More recently, Bauer and coworkers [44]
have investigated the effects of arzanol on the biosynthesis of prostanoids and LTs and have evaluted its anti-
inflammatory efficacy in vitro and in vivo. They have shown that this molecule potently inhibits the inducible
microsomal prostaglandin (PG)E2 synthase (EC 5.3.99.3), COX-1(EC 1.14.99) and 5-LO (EC 7.13.11.34) in vitro with
IC50 values ranging from 0.4 to 9 µM. In vivo, arzaanol suppresses the inflammatory response of the carrageenan-
induced pleurisy in rats (3.6 mg/kg, intraperitoneal) with significantly reduced levels of PGE2 (2.27 ng/rat) in the
pleural exudates. Taken together, all these findings show that arzanol act as potent dual-inhibitor of pro-inflammatory
mediators and inflammatory enzymes, providing a mechanistic rationale for the well-known anti-inflammatory activity
of H. italicum. Moreover, this compound displays a large spectrum of properties including anti-oxidant and anti-viral
activities (see sections 3.3 and 3.4).
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3.3. Anti-viral activity
A few studies of the anti-viral properties of H. italicum extracts and their constituents have been published. It has been
pointed out that a diethyl ether extract, obtained from the flowering tops of H. italicum, possesses significant activity
against the herpes simplex virus type 1 (HSV-1) at concentrations ranging from 100 to 400 µg/mL. Moreover, this
extract has no genotoxic effect since it does not provoke DNA damages at concentrations up to 200 µg per disk [45]. In
a more recent study, Appendino and coworkers [18] have shown that arzanol inhibits the HIV-1 replication in T cells.
This anti-HIV activity was further investigate by infecting Jurkat cells with the pNL4-3 HIV-1 clone pseudotyped with
the VSV envelope, which can supports a robust HIV-1 replication. Upon integration into host chromosomes, this
recombinant virus expresses the firefly luciferase gene, and therefore, luciferase activity in infected cells correlates with
the rate of viral replication. A pretreatment of Jurkat cells 30 min prior to infection with increasing doses of arzanol
resulted in a dose-dependent inhibition of luciferase activity.
3.4. Antioxidant activity
Some flavonoids constituents of H. italicum exhibit antioxidant activities, which are closely related to their anti-
inflammatory effects. In a study investigated by Sala and coworkers [46], whose purpose was to assess the antioxidant
properties of three flavonoids (gnaphaliin, pinocembrin and tiliroside) isolated from the aerial parts of H. italicum, the
tiliroside was identified as the most active compound. More precisely, the scavenger properties of these flavonoids were
tested first in vitro and then in vivo by means of different models of inflammation. Tiliroside shows significant
inhibition of enzymatic and non-enzymatic lipid peroxidation (IC50 values: 12.6 and 28 µM respectively). It has
scavenger properties (IC50 = 21.3 µM) and very potent antioxidant activity in the reduction of stable radical 1,1-
diphenyl-2-pycryl-hydrazyl (DPPH) test (IC50 = 6 µM). In vivo, it significantly reduces the mouse paw oedema induced
by phospholipase A2 (ID50 = 35.6 mg/kg) and the mouse ear inflammation induced by TPA (ID50 =
0.357 mg/ear).
Recently, the protective effect in lipid peroxidation of azarnol was highlighted. Its antioxidant activity was assessed
against the oxidative modification of lipid components induced by Cu2+ ions in human low density lipoprotein (LDL)
and by tert-butyl hydroperoxide (TBH) in cell membranes. In vitro, LDL pretreatment with azarnol significantly
preserves lipoproteins from oxidative damage at 2 h of oxidation and exerts a remarkable reduction of polyunsaturated
fatty acids and cholesterol levels. At non-cytotoxic concentrations, it also protects VERO cells against TBH induced
oxidative stress [47]. So, azarnol can be qualified as a potent natural antioxidant with a protective effect against lipid
oxidation in biological systems.
3.5. Anti-larvicidal activity
Only a few reports describe the effects of H. italicum against insects. It has been recently shown that the EO isolated
from the leaves of H. italicum, growing on Elba Island, induces larval mortality of the Culicidae mosquito Aedes
albopictus at 300 ppm with mortality rates ranging from 98.3% to 100% [38]. Use of botanical derivatives in mosquito
control, instead of synthetic insecticides, is thought to be harmless to humans and other nontarget organisms. So, further
investigations are needed to identify natural mosquitocidal compounds, which could be utilized in commercial
formulations.
4. Conclusion
In conclusion, this survey of the literature showed that H. italicum sp exhibits interesting biological activities that seem
to be due to the large diversity of its chemical contents. These remarkable properties explain the enthusiasm that exists
around H. italicum sp essential oil and extracts. However, care should be taken to the species or species derivatives,
maturation state, part of the plant used, and to the extraction procedures that are undertaken to produce bio-active
extracts.
References
[1] Perrini R, Morone-Fortunato I, Lorusso E, Avato P. Glands, essential oils and in vitro establishment of Helichrysum italicum
(Roth) G. Don ssp. microphyllum (Willd.) Nyman. Industrial Crops and Products. 2009; 29: 395-403.
[2] Jeanmonod D., Gamisans J. Flora Corsica, Edisud, 2007.
[3] Schiller C and Schiller D. The Aromatherapy Encyclopedia: A Concise Guide to Over 385 Plant Oils. 2008: 121.
[4] Maffei FR, Carini M, Mariani M, Cipriani C. Anti-erythematous and photoprotective activities in guinea pigs and in man of
topically applied flavonoids from Helichrysum italicum G. Don. Acta Therapeutica. 1988; 14: 323-345.
[5] Maffei FR, Carini M, Franzoi L, Pirola O, Bosisio E. Phytochemical characterization and radical scavenger activities of
flavonoids from Helichrysum italicum G. Don (Compositae). Pharmacological Research. 1990; 22: 709-720.
Microbial pathogens and strategies for combating them: science, technology and education (A. Méndez-Vilas, Ed.)
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[6] Mancini E, De Martino L, De Falco E, Di Novella N, De Feo V. Usi populari di specie vegetali nel Vallo di Diano (Salerno).
Italian Journal of Agronomy. 2009; 4: 387-396.
[7] Voinchet V, Giraud-Robert AM. Utilisation de l’huile essentielle d’hélichryse italienne et de l’huile végétale de rose musquée
après intervention de chirurgie plastique réparatrice et esthétique. Phytothérapie. 2007; 5: 67-72.
[8] Peace Rhind Jennifer. Essential Oils: A Handbook for Aromatherapy Practice. 2012: 148-149.
[9] Di Modica G, Tira S. Sostanze isolate da Helichrysum italicum G. Don: Frazini neutre. Annali di Chimica. 1958; 48: 681-689.
[10] Tira S, Di Modica G, Rossi PF. Isolamento e riconoscimento di acidi presenti in Helichrysum italicum G. Don. Atti
dell’Academia, Scienze Fisiche. 1959; 94: 185-190.
[11] Taglialatela-Scafati O, Pollastro F, Chianese G, Minassi A, Gibbons S, Arunotayanun W, Mabebie B, Ballero M, Appendino G.
Antimicrobial phenolics and unusual glycerides from Helichrysum italicum subsp. microphyllum. Journal of Natural Products.
2013; 76: 346-353.
[12] Zapesochnaya, GG, Dzyadevich TV, Karasartov BS. Phenolic compounds of Helichrysum italicum. Chemistry of Natural
Compounds. 1990; 26: 342-343.
[13] Mezzetti T, Orzalesi G, Rossi C, Bellavita V. A new triterpenoid lactone, α-amyrin and uvaol from Helichrysum italicum.
Planta Medica. 1970; 18: 326-331.
[14] Wollenweber E, Christ M, Dunstan RH, Roitman JN, Stevens JF. Exudate Flavonoids in Some Gnaphalieae and Inuleae
(Asteraceae). Zeitschrift für Naturforschung. 2005; 60c: 671-678.
[15] Sala A, del Carmen Recio M, Giner RM, Máñez S, Ríos JL. New Acetophenone Glucosides Isolated from Extracts of
Helichrysum italicum with Antiinflammatory Activity. Journal of Natural Products. 2001; 64: 1360-1362.
[16] Appendino G, Ottino M, Marquez N, Bianchi F, Giana A, Ballero M, Sterner O, Fiebich BL,| Munoz E. Arzanol, an anti-
inflammatory and anti-hiv-1 phloroglucinol α-pyrone from Helichrysum italicum ssp. microphyllum. Journal of Natural
Products. 2007; 70: 608-612.
[17] Rosa A, Deiana M, Atzeri A, Corona G, Incani A, Melis MP et al. Evaluation of the antioxidant and cytotoxic activity of
arzanol, a prenylated alpha-pyrone-pholoroglucinol etherodimer fom Helichrysum italicum subsp microphyllum. Chemico-
Biological Interactions. 2007; 165: 117-126.
[18] Tira S, Di Modica G. New β-diketones from Helichrysum italicum G. Don. Tetrahedron Letters. 1967; 143-149.
[19] Manitto P, Monti D, Colombo E. Two new β-diketones from Helichrysum italicum. Phytochemistry. 1972; 11: 2112-2114.
[20] Bianchini A, Tomi F, Richomme P, Bernardini AF, Casanova J. Eudesm-5-en-11-ol from Helichrysum italicum essential oil.
Magnetic Resonance in Chemistry. 2004; 42: 983–984.
[21] Roussis V, Tsoukatou M, Petrakis PV, Chinou I, Skoula M, Harborne JB. Volatile, constituents of four Helichysum species
growing in Greece. Biochemical Systematics and Ecology. 2000; 28: 163-175.
[22] Satta M, Tuberoso CIG, Angioni A, Pirisi FM, Cabras P. Analysis of the essential oil of Helichrysum italicum G. Don ssp.
microphyllum (Willd) Nym. Journal of Essential Oil Research. 1999; 11: 711-715.
[23] Marongiu B, Piras A, Desogus E, Porcedda S, Ballero M. Analysis of the volatile concentrate of the leaves and flowers of
Helichrysum italicum (Roth) G. Don ssp. microphyllum (Willd) Nyman (Asteraceae) by supercritical fluid extraction and their
essential oils. Journal of Essential Oil Research. 2003; 15: 120-126.
[24] Usai M, Foddai M, Bernardini AF, Muselli A, Costa J, Marchetti M. Chemical composition and variation of the essential oil of
wild Sardinian Helichrysum italicum G. Don subsp. microphyllum (Willd) Nym. fom vegetative period to post-blooming.
Journal of Essential Oil Research. 2010; 22: 373-380.
[25] Bianchini A, Tomi P, Bernardini AF, Morelli I, Flamini G, Cioni PL, Usaï M, Marchetti M. A comparative study of volatile
constituents of two Helichrysum italicum (Roth) Guss. Don Fil subspecies growing in Corsica (France), Tuscany and Sardinia
(Italy). Flavour Fragrance Journal. 2003; 18: 487–491.
[26] Mancini E, De Martino L, Marandino A, Scognamiglio MR, De Feo V. Chemical Composition and Possible in Vitro Phytotoxic
Activity of Helichrsyum italicum (Roth) Don ssp. italicum. Molecules 2011; 16: 7725-7735.
[27] Morone-Fortunato I, Montemurro C, Ruta C, Perrini R, Sabetta W, Blanco A, Lorusso E, Avato P. Essential oils, genetic
relationships and in vitro establishment of Helichrysum italicum (Roth) G. Don ssp. italicum from wild Mediterranean
germplasm. Industrial Crops and Products. 2010; 32: 639-649.
[28] Chinou IB, Roussis V, Perdetzoglou D, Loukis A. Chemical and biological studies of two Helichysum species of Greek origin.
Planta Medica. 1996; 62: 377-379.
[29] Bianchini A, Tomi P, Costa J, Bernardini AF. Composition of Helichrysum italicum (Roth) G. Don fil. subsp. italicum essential
oils from Corsica (France). Flavour Fragrance Journal. 2001; 16: 30–34.
[30] Paolini J, Desjobert JM, Costa J, Bernardini AF, Buti Castellini C, Cioni PL, Flamini G, Morelli I. Composition of essential oils
of Helichrysum italicum (Roth) G. Don fil subsp. italicum from Tuscan archipelago islands. Flavour Fragrance Journal. 2006;
21: 805–808
[31] Leonardi M, Ambryszewska KE, Melai B, Flamini G, Cioni PL, Parri F, Pistelli L. Essential-oil composition of Helichrysum
italicum (Roth) G. Don ssp. italicum from Elba Island (Tuscany, Italy). Chemistry and Biodiversity. 2013; 10: 343-355.
[32] Weyerstahl P, Marschall-Weyerstahl H, Weirauch M, Meier N, Manteuffel E, Leimner J, Sholtz S. Isolation and Synthesis of
compounds from the essential oil of Helichrysum italicum. In Progress in Essential Oil Research, Brunke ES (eds). Walter de
Gruyter: Berlin, 1986; 178-195.
[33] Blažević N, Petričić J, Stanić G, Maleš Ž. Variations in yields and composition of immortelle (Helichrysum italicum, Roth
Guss.) essential oil from different locations and vegetation periods along Adriatic coast. Acta Pharmaceutica. 1995; 45: 517-
522.
[34] Mastelic J, Politeo O, Jerkovic I, Radosevic N. Composition and antimicrobial activity of Helichrysum italicum essential oil and
its terpene and terpenoids fractions. Chemistry of Natural Compounds. 2005; 41: 35-39.
[35] Conti B, Canale A, Bertoli A, Gozzini F, Pistelli L. Essential oil composition and larvicidal activity of six Mediterranean
aromatic plants against the mosquito Aedes albopictus (Diptera: Culicidae). Parasitology Research. 2010; 107: 1455-1461.
Microbial pathogens and strategies for combating them: science, technology and education (A. Méndez-Vilas, Ed.)
© FORMATEX 2013
____________________________________________________________________________________________
1079
[36] Bertoli A, Conti B, Mazzoni V, Meini L, Pistelli L. Volatile chemical composition and bioactivity of six essential oils against
the stored food insect Sitophilus zeamais Motsch. (Coleoptera Dryophthoridae). Natural Product Research. 2012; 26: 2063-
2071.
[37] Bianchini A, Santoni F, Paolini J, Bernardini AF, Mouillot D, Costa J. Partitioning the Relative Contributions of Inorganic
Plant Composition and Soil Characteristics to the Quality of Helichrysum italicum subsp. italicum (Roth) G. Don fil. Essential
Oil. Chemistry and Biodiversity. 2009; 6: 1014-1033.
[38] Nostro A, Bisignano J, Cannatelli MA, Crisafi G, Germano MP, Alonzo V. Effects of Helichrysum italicum extract on growth
enzymatic activity of Staphylococcus aureus. International Journal of Antimicrobial Agents. 2001 ;17: 517-520.
[39] Nostro A, Cannatelli MA, Musolino AD, Procopio F, Alonzo V. Helichrysum italicum extract interferes with the productions of
enterotoxins by Staphylococcus aureus. Letters in Applied Microbiology. 2002; 35: 181-184.
[40] Nostro A, Cannatelli MA, Crisafi G, Musolino AD, Procopio F, Alonzo V. Modifications of hydrophobicity, in vitro adherence
and cellular aggregation of Streptococcus mutans by Helichrysum italicum extract. Letters in Applied Microbiology.2004; 38:
423-427.
[41] Rossi PG, Berti L, Panighi J, Luciani A, Maury J, Muselli A. De Rocca Serra D, Gonny M, Bolla JM. Antibacterial action of
essential oils from Corsica. Journal of Essential Oil Research. 2007; 19: 176-182.
[42] Burt SA. Essential oils: their antibacterial properties and potential applications in food: a review. International Journal of Food
Microbiology. 2004; 94: 223-253.
[43] Lorenzi V, Muselli A, Bernardini AF, Berti L, Pages JM, Amaral L, Bolla JM. Geraniol restores antibiotic activities against
multidrug-resistant isolates from gram-negative species. Antimicrobial agents and chemotherapy. 2009; 53: 2209-2211.
[44] Bauer J, Koeberle A, Dehma F, Pollastro F, Appendino G ,Northoff H, Rossi A, Sautebin L, Werz O. Arzanol, a prenylated
heterodimeric phloroglucinyl pyrone, inhibits eicosanoid biosynthesis and exhibits anti-inflammatory efficacy in vivo.
Biochemical Pharmacology. 2011; 81: 259-268.
[45] Nostro A, Cannatelli MA, Marino A, Picerno I, Pizzimenti FC, Scoglio ME, Spataro P. Evaluation of antiherpesvirus-1 and
genotoxic activity of Helichrysum italicum extract. Microbiologica. 2003; 26: 125-128.
[46] Sala A, Recio MC, Schinella GR, Máñez S, Giner RM, Cerdá-Nicolás M, Ríos JL. Assessment of the anti-inflammatory activity
and free radical scavenger activity of tiliroside. European Journal of Pharmacology. 2003; 461: 53-61.
[47] Rosa A, Pollastro F, Atzeri A, Appendino G, Melis MP, Deiana M, Incani A, Loru D, Dessì MA. Protective role of arzanol
against lipid peroxidation in biological system. Chemistry and Physics of Lipids. 2011; 164: 24-32.
Microbial pathogens and strategies for combating them: science, technology and education (A. Méndez-Vilas, Ed.)
© FORMATEX 2013
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