Industrial Crops & Products 138 (2019) 111471
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Industrial Crops & Products
journal homepage: www.elsevier.com/locate/indcrop
Everlasting flowers: Phytochemistry and pharmacology of the genus
Helichrysum
Maryam Akaberia, Amirhossein Sahebkarb,c, Narjes Azizid, Seyed Ahmad Emamia,e,
T
⁎
a
Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
c
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
d
Forest and Rangeland Research Department, Khorasan Razavi Agricultural and Natural Resources Research and Education Center. AREEO, Mashhad, Iran
e
Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
b
A R TICL E INFO
A BSTR A CT
Keywords:
Helichrysum
Phytochemistry
Pharmacology
Phloroglucinols
Pyrones
Anti-microbial
The plants belonging to the genus Helichrysum (Asteraceae) are known as everlasting flowers and widely used in
traditional medicine worldwide. Surveys on their traditional uses as well as phytochemical and pharmacological
studies have revealed the potential of these plants for drug discovery. Although there are several studies on some
of the species, most of the plants need to be investigated thoroughly. The aim of this review is to present a
collated and coherent overview of the documented traditional uses, pharmacological activities and particularly
bioactive constituents of Helichrysum species. Scientific databases including Scifinder, ISI Web of Knowledge,
PubMed and Scopus as well as several traditional texts and books were searched to collect the data. Review of
studies showed that Helichrysum spp. have been used in different systems of traditional and folk medicines for the
treatment of various infections, wounds, digestive problems, diabetes and colds, of which some are confirmed in
modern medicine such as the antimicrobial activity. Phytochemical investigations have shown that these plants
are rich in phenolic compounds such as flavonoids, pyrones, phloroglucinols and essential oils, and in some
species terpenes such as sesquitepenes and diterpenes are dominant. However, among these compounds, pyrones
and phloroglucinols have been reported to be the bioactive constituents in most of the studies. Overall, according
to the potential of these plants, further phytochemical, ethnopharmacological and pharmacological studies are
required since only a few species have been investigated so far.
1. Introduction
Helichrysum genus belonging to Asteraceae family consists of about
600 species worldwide. It is originally from Africa (244 species in South
Africa), Madagascar, Australasia and Eurasia. The name of the genus is
derived from the Greek words “helios” and “chryos”, which mean “sun”
and “gold”, respectively. This nomenclature is due to the fact that the
plant species of this genus typically have inflorescences of a bright
yellow color (Perrini et al., 2009). The common names of the plants are
everlasting flowers and immortelles since they retain their form and
color when dried and are used in dry bouquets and flower arrangements. Some species like H. arenarium are also called the golden flower
referring to the golden color of the flowers.
From a systematic point of view, Helichrysum Mill. is a large genus,
with a worldwide distribution (Azizi et al., 2014a, b; Azizi et al., 2019).
The most well-known and studied species of this genus are H. italicum
(Antunes Viegas et al., 2014), H. stoechas (Les et al., 2017), and H.
arenarium (Pljevljakušić et al., 2018). Studies show that Helichrysum
spp. are very rich in phenolic compounds mainly phloroglucinol derivatives and flavonoids (Bohlmann et al.,). Helichrysum spp. have been
used as flavoring spices in a variety of foods and folk medicines, and for
cosmetic purposes for centuries (Antunes Viegas et al., 2014). In addition, Helichrysum spp. have potential pharmacological applications
for their antioxidant, antimicrobial, and anti-inflammatory activities
(Taglialatela-Scafati et al., 2013; Mao et al., 2017).
Considering the important role that the Helichrysum spp. play in the
Abbreviations: CRP, c-reactive protein; DPP-IV, dipeptidyl peptidase-IV; EMA, European medicines agency; HIV, human immunodeficiency virus; IL-1β, interleukin1β; IL-6, interleukin-6; IL-8, interleukin-8; JNK, c-Jun N-terminal kinases; MAPK, mitogen-activated protein kinase; MIC, minimum inhibitory concentration; mPGES1, microsomal prostaglandin E synthase-1; NO, nitric oxide; PGE2, prostaglandin E2; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor; WHO,
World Health Organization
⁎
Corresponding author at: Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
E-mail address: emamia@mums.ac.ir (S.A. Emami).
https://doi.org/10.1016/j.indcrop.2019.111471
Received 11 March 2019; Received in revised form 25 April 2019; Accepted 9 June 2019
0926-6690/ © 2019 Elsevier B.V. All rights reserved.
Name
Traditional use
Country/Region
Plant part/preparation
Ref.
H. adenocarpum DC.
Diarrhea and vomiting in children
South Africa
Roots/decoction
Chest problems or infection of the respiratory tract
Smallpox
Anthelmintic
Coughs and colds and applied externally on wounds
Relax body and to reduce swelling
South
South
South
South
South
H. argyrophyllum DC.
Intestinal problems
South Africa
Leaf eaten raw
Whole plant/wound dressing
Whole plant/wound dressing
Root/wound dressing
Root/ ground and burnt and
smeared on the body
Root as infusion
(Jacot Guillarmod, 1971; Neuwinger, 1996; Phillips,
1917)
(Arnold et al., 2002; Githens, 1949)
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
arenarium
athrixiifolium (Kuntze) Moeser
caespititium (DC.) Harv
caespititium (DC.) Harv
caespititium (DC.) Harv
callicomum Harv
calophalum Klatt
cochleariforme DC.
cochleariforme DC.
cooperi Harv
crispum (L.) D. Don
crispum (L.) D. Don
crispum (L.) D. Don
dregeanum Sond.
ecklonis Sond
faradifani
H.
H.
H.
H.
H.
H.
H.
foetidum (L.) Moench
foetidum (L.) Moench
foetidum (L.) Moench
foetidum (L.) Moench
fulgidum (L.f.) Willd
graveolens
italicum
Antiseptic, coleretic and spasmolytic agent
Chest complaints
Headaches
Nausea, virility
Wound healing
Colic
Hyperfunction of the lower gastro-intestinal tract
Coughs
Infections of the respiratory tract
Used as love charm
Coughs, bronchitis, urinary tract infections and tuberculosis
Colds and coughs
Emetic and purgative
Head cold
Diarrhea in children
A wound-healing and disinfectant agent, disinfectant, syphilis, diarrhea, cough and
headache
Infected sores
Influenza
Infected wounds, and herpes
Eye problems
Used for washing sore eyes
Controlling the symptoms of diabetes mellitus, wound healing and as a diuretic
Toothache, digestive disorders and catarrh, analgesic, anti-odontalgic, astringent,
antiemetic and dermatologic tonic, allergy, stomach cleanser, cough, colds, tracheitis and
laryngitis, skin diseases, and mouth antiseptic, liver and gall disorders, sleeplessness,
headache, sniffles, helmintic infections, asthma
Coughs and pulmonary tuberculosis
Wounds
Bronchitis, cough and pharyngitis, cardiotonic
H.
H.
H.
H.
H.
appendiculatum
appendiculatum
appendiculatum
appendiculatum
appendiculatum
(L.f.)
(L.f.)
(L.f.)
(L.f.)
(L.f.)
Less.
Less.
Less.
Less.
Less.
2
H. kraussii Sch. Bip
H. longifolium DC.
H. melaleucum Rchb.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
nudifolium var. leiopodium
nudifolium var. leiopodium
nudifolium var. leiopodium
obconicum DC
odoratissimum (L.) Sweet
odoratissimum (L.) Sweet
odoratissimum (L.) Sweet
orientale (L.) Vaill
panduratum O. Hoffm.
pandurifolium Schrank.
Intestinal parasites
Chest complaints
Respiratory infections
Headache
Colic in children
Stomach and intestinal disorders
Wounds and burns
Headache
Tonic for pregnant women
Asthma and cough
Malaria
Respiratory conditions, back pain, heart trouble, kidney disease, and kidney stones
Africa
Africa
Africa
Africa
Africa
Africa
South Africa
South Africa
South Africa
South Africa
South Africa
South Africa
South Africa
Madagascar
South
South
South
South
South
Africa
Africa
Africa
Africa
Africa
(Arnold et al., 2002; Batten and Bokelmann, 1966;
Walker, 1996; Watt and Breyer-Brandwijk, 1962)
Leaf as smoke
Whole plant/smoke
Root as decoction
Whole plant/ointment
Enema
Root
Infusion
Whole plant/decoction
Leaf/ointment
(Arnold et al., 2002; Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
Leaf as decoction
Root/extract
Leaf/smoke
Root/decoction
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Benelli et al., 2018)
Leaves/poultice
Leaf/extract
Leaf/wound dressing
Root/extract
Decoction
(Grierson and Afolayan, 1999)
(Lourens et al., 2008)
(Lourens et al., 2008)
Europe
Aerial parts
(Antunes Viegas et al., 2014)
South Africa
South Africa
Portugal
Flower and seed/smoke
Leaf
Flower heads and leaves/
infusion
Tea
Whole plant/decoction
Root
Leaf/smoke inhalation
Decoction as enema
Flower and leaves/infusion
Leaf/wound dressing
Leaf/smoke
Leaf/decoction
Flowers/infusion
Whole plant/sap
Infusion
(Lourens et al., 2008)
(Lourens et al., 2008)
(Rivera and Obón, 1995)
South Africa
South Africa
South Africa
South Africa
South Africa
Portugal
South Africa
South Africa
South Africa
Portugal
South Africa
South Africa
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Rivera and Obón, 1995)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Rivera and Obón, 1995)
(Lourens et al., 2008)
(Lourens et al., 2008)
(continued on next page)
Industrial Crops & Products 138 (2019) 111471
H. miconiifolium DC.
South
South
South
South
South
South
Africa
Africa
Africa
Africa
Africa
M. Akaberi, et al.
Table 1
The traditional uses of Helichrysum spp. in different parts of the world.
Industrial Crops & Products 138 (2019) 111471
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Bigovic et al., 2010; Polat et al., 2013; Yeşilada et al.,
1995)
(Tetik et al., 2013)
(Polat et al., 2013)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Lourens et al., 2008)
(Antunes Viegas et al., 2014)
(Antunes Viegas et al., 2014)
South Africa
South Africa
Turkey
Turkey
Turkey
South Africa
South Africa
South Africa
South Africa
Spain
Spain
Coughs, colds, catarrh, headache, fever, menstrual disorders, and urinary tract infections
Renew virility in men
Gastric and hepatic disorders, jaundice, dysuria and kidney stones
Wounds
Diabetes
Dysmenorrhea
Colic
Epilepsy
Rheumatism
Toothache, urologic conditions and digestive disorders
Conjunctivitis and ocular infections, pharyngitis and tonsillitis, wounds, hemorrhoids,
intestinal parasitic infections, toothache, kidney disorders
Headaches
Sore eyes
Bladder problems
3. Traditional uses
All over the world, the plants of genus Helichrysum has been used in
traditional medicine for at least 2000 years. These plants have traditionally been used for ornamental, medicinal and food purposes
(Antunes Viegas et al., 2014). For instance, H. italicum subsp. picardii is
an aromatic halophyte common in southern Europe frequently used as a
spice and traditional medicine.
Generally, everlasting flowers have been used mainly in different
traditional medicines as an infusion or decoction; for example, H.
stoechas Moench infusion has been used traditionally to treat diverse
disorders such as influenza and cold, fever, nervousness, as well as
gallbladder, urinary bladder, digestive and pancreas problems (Benítez
et al., 2010). The preparation of H. arenarium in the form of an infusion
or decoction that is based on its traditional use for treating digestive
problems (e.g. fullness and bloating) has been approved by the World
Health Organization (WHO) and the European Medicines Agency
(EMA).
Table 1 shows the application of different Helichrysum spp. in various traditional medicine. These data show that the most frequently
reported traditional uses of Helichrysum spp. are related to its antimicrobial properties. However, it has been also used as an analgesic
agent and for the treatment of diabetes and digestive problems.
South Africa
South Africa
South Africa
Leaf and root/infusion
Leaves
South Africa
South Africa
4. Phytochemistry
Lloyd et al. was the first group who investigated the phytochemical
composition of the plants belonging to the genus Helichrysum in 1967
by working on the species H. dendroideum (Bohlmann and Zdero, 1973),
of which some terpene alcohols were isolated. Other studies on this
genus confirmed the presence of terpenoids and essential oils as one of
the main classes of secondary metabolites. However, further studies by
other research groups on the genus showed that phenolic and oxygenated compounds contributed the major components. The reported
secondary metabolites from the genus can be categorized into six
structural types: flavonoids and chalcones, phenolic acids, terpenes and
essential oils, pyrones (both homo- and heterodimeric), benzofurans
(bitalin esters) and phloroglucinols (Taglialatela-Scafati et al., 2013)
consisting mainly of two types of substituents: a prenyl/geranyl group
and an acyl group. The most common acyl substituents are methyl,
isopropyl, and 2-methylbutanoyl.
The isolated pyrones from Helichrysum spp. can be either monomers
such as the compound micropyroe 1 and glycosylated forms of yangonin 2-3 (acylated styrylpyrones) (D’ Abrosca et al., 2013) or they can
be hetero- and homo-dimers (Fig. 1 and Table 6); helipyrone A 4 (Opitz
and Hänsel, 1970), B 5, and C 6 (Vrkcoč et al., 1975) are examples of
H. stoechas
H. stoechas
H. plicatum
H. plicatum
4.1. Pyrones
H. plicatum
H. pedunculatum Hilliard and Burtt
H. pedunculatum Hilliard &
B.L.Burtt
H. petiolare Hilliard and Burtt
Infusion
South Africa
Heart trouble, backache, kidney disease, coronary thrombosis, bladder conditions/
infections, asthma, and influenza
Antiseptic
Inflammation and wounds
H. patulum (L.). Don.
The selection of relevant data was made through a search using the
keyword “Helichrysum” in scientific databases such as “SciFinder”,
“Google Scholar”, “ISI Web of Knowledge”, “PubMed”, “ScienceDirect”
and “Wiley Online Library”. Information obtained in local and foreign
books and other sources including several traditional texts and books
were used to collect the information. Table 7 shows the scientific names
of Helichrysum taxa reviewed in this paper.
Leaf/tea
Root/decoction
Flowers as infusion, and
decoction
Ointment as infusion
Flowers as infusion
Root/decoction
enema
Leaf/decoction
Roots
Flowers as infusion
Flowers and stems as decoction
and ointment
Aerial parts/smoke inhalation
Decoction
Root/decoction
(Lourens et al., 2008)
(Bhat and Jacobs, 1995)
2. Search strategy
Country/Region
(Lourens et al., 2008)
traditional medicinal practices of many countries around the world,
reviewing the studies and investigations about these valuable plants
could be helpful for future drug discovery investigations. The present
review deals with the traditional uses and pharmacological studies of
Helichrysum spp. In addition, this review introduces the bioactive
compounds isolated from the genus.
Traditional use
Name
Table 1 (continued)
Plant part/preparation
Ref.
M. Akaberi, et al.
3
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M. Akaberi, et al.
Fig. 1. Pyrones from Helichrysum spp.
homo-dimer pyrones. Hetero-dimer pyrones are reported to consist of
one phloroglucinol ring attached to an α-pyrone moiety via a methylene
bridge. Bohlmann et al. (1980) isolated 23-methylauricepyrone 7 as a
mixture with norauricepyrone 8 from H. auriceps (Bohlmann and Zdero,
1980b). Appendino et al. (2001) isolated and identified arzanol 9 and
arenol 10 as novel prenylated phloroglucinol α-pyrones from H. italicum (Roth) Don spp. Microphyllum (Appendino et al., 2007a; Lavault
and Richomme, 2004). Although the presence of a prenyl side chain is
typical to these heterodimers like 9-14 (Appendino et al., 2007a;
Akaberi et al., 2019), 7, 16 (Bohlmann and Zdero, 1980b), and 24
(Rosa et al., 2007), in some reported structures it can be absent (norauricepyrone 8) (Jakupovic et al., 1986), rearranged (heliarzanol, 15)
(Taglialatela-Scafati et al., 2013), or doubled as a geranyl group (17-23
isolated from H. decumbens) (Tomás-Barberán et al., 1990; TomásLorente et al., 1989; Akaberi et al., 2019). Not only hetero-dimers but
also hetero-trimers with two α-pyrone rings have been found from the
genus, for instance, 23-methylitalidipyrone 25 and italidipyrone 26
from H. italicum (Hänsel et al., 1980).
4
Industrial Crops & Products 138 (2019) 111471
M. Akaberi, et al.
Fig. 2. Phloroglucinols from Helichrysum spp.
As abovementioned, in some derivatives, the prenyl or geranyl
groups are rearranged and create new scaffolds. They may undergo
cyclization leading to the formation of chromane and benzofuran derivatives such as compounds italipyrone 27, 20-prenylitalipyrone 28,
plicatipyrone 29, isobutyrylhelichromenopyrone 30, 2-methylbutyrylhelichromenopyrone 31, helicerastripyrone 32 (Bohlmann et al.,
1984; Hänsel et al., 1980; Rios et al., 1991), helicepyrone 33, cycloarzanol 34, and helicyclol 35 (Akaberi et al., 2019). Lepidissipyrone
36 and 8-prenyllepidissipyrone 37 are examples of a chromanone
moiety in the molecules isolated from H. lepidissimum (Jakupovic et al.,
1989b). In a recent study, two new pyrone derivatives Helitalone A 38
and B 39 have been isolated and identified from H. italicum (Werner
et al., 2019). Interestingly, these compounds are the first examples of
pyrones reported from Helichrysum genus bearing an isopropyl and 1butyl substitutes in the pyrone ring moieties.
It is noteworthy that in arzanol 9 or other α-pyrone phloroglucinols,
the presence of several hydrogen bond donor or acceptor sites makes
intramolecular hydrogen bonding patterns the dominant stabilizing
factor. The lowest energy conformers have the highest number of
stronger intramolecular hydrogen bonds (Mammino, 2017). In this
case, thanks to the presence of an acyl group (COR group) whose sp2 O
can form an intramolecular hydrogen bond with one of the two ortho
OHs, and the presence of an α-pyrone ring which is attached to one
position meta to the COR group, arzanol can form up to three OeH···O
bonds simultaneously (Mammino, 2017).
5
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M. Akaberi, et al.
Fig. 3. Benzofurans and phtalides from Helichrysum spp.
et al., 1986; Popoola et al., 2015b). Some reported phloroglucinols from
this genus include helinudifolin 40, 41 (Jakupovic et al., 1986), helinivene A 42 and B 43, 1-(butanone)-3-prenyl-phloroglucinol 44, 1-(2methylbutanone)-3-prenyl-phloroglucinol
45,
1-butanone-3-(3-
4.2. Phloroglucinols
Phloroglucinols as homo-dimers and monomers are another class of
secondary metabolites present in most of the studied species (Jakupovic
Table 2
Flavonoids and phenolic acids reported from Helichrysum spp.
Helichrysum spp.
Compound (s)
Activity
Ref.
H. arenarium subsp.
arenarium
Caffeic acid conjugates (chlorogenic acid and dicaffeoylquinic acids) and
flavonoids (apigenin, naringenin, apigenin-7-O-glucoside and naringenin-Ohexosides)
Naringenin-7-O-β-d-glycoside, isoquercitrin, and astragalin
Galangin
Antibacterial
(Gradinaru et al., 2014)
_
Antibacterial and
antioxidant
Antifungal
(Yang et al., 2009)
(Cushnie and Lamb, 2006; De
La Puerta et al., 1999)
(Tomás-Lorente et al., 1989)
_
(Gouveia and Castilho, 2009)
Atimicrobial
(Malolo et al., 2015)
Anti-biofilm
_
(D’Abrosca et al., 2013)
(Karasartov et al., 1992)
Anticarcinogenic
Antimicrobial
_
(Yagura et al., 2008)
(Malolo et al., 2015)
(Gouveia and Castilho, 2011)
_
(Mutanyatta-Comar et al.,
2006)
Antioxidant
Antioxidant
(Aiyegoro and Okoh, 2009)
(Carini et al., 2001)
Antioxidant
(Popoola et al., 2015a)
H. arenarium (L.) Moench
H. aureonitens
H. decumbens
H. devium
H. foetidum (L.) Moench
H. italicum
H. italicum
H. maracandicum
H. mechowianum Klatt.
H. obconicum
H. paronychioides
H. pedunculatum
H. stoechas
H. teretifolium
3,5-dihydroxy-6,7,8-trimethoxyflavone, 5,7-dihydroxy-3,6,8-trimethoxy-flavone
and 3,5-dihydroxy-6,7-dimethoxyflavone
Quinic acid derivatives, O-glycosylated flavonoids, caffeic acid derivatives and a
protocatechuic acid derivative
7, 4′-dihydroxy-5-methoxy-flavanone, 6′-methoxy-2′,4, 4′-trihydroxychalcone, 6′methoxy-2′,4-dihydroxychalcone -4′-O-β-D-glucoside, apigenin (4), apigenin-7-Oβ-D-glucoside, kaur-16-en-18-oic acid
Lignans, and quinic acid derivatives
Kaempferol, 3,5,7-trihydroxy-8-methoxyflavone and 3,5-dihydroxy-6,7,8trimethoxyflavone
Naringenin chalcone, and isosalipurposide
3,5,7-trihydroxy-8-methoxyflavone, and 4,5-dicaffeoyl quinic acid
Quinic acid deriavtives, caffeoylquinic acid, malonylcaffeoylquinic acid,
coumaroylquinic acid, and caffeoylshikimic acids
3-methylquercetin, 3,3´-dimethylquercetin, 3,7-dimethylkaempferol, penduletin,
eupalitin, 2-(2-methylpropanoyl)-4-prenylphloroglucinol, and 2-(2methylbutanoyl)-4-prenylphloroglucinol
Flavonoids, proanthocyanidin and phenolic contents
Neo-chlorogenic acid, chlorogenic acid and crypto-chlorogenic acid, isomeric
dicaffeoyl quinic acids, isomeric naringenin glucosides, quercetin, kaempferol and
apigenin glucosides and a tetrahydroxychalcone-glucoside
Isoxanthohumol, 2',4',6'-trihydroxy-3'-prenylchalcone, isoglabranin, glabranin,
quercetin and compounds 44-48
6
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M. Akaberi, et al.
Fig. 4. Flavonoids and chalcones from Helichrysum spp.
1989b) (Fig. 2 and Table 6). Recently, helispiroketals A–H 58-65,
phloroglucinol derivatives bearing an α,β-unsaturated spiroketal unit
with five-membered rings, have been isolated from the endemic Iranian
H. oocephalum (Akaberi et al., 2019).
methylbut-2-enylacetate)-phloroglucinol 46, 1-(2-methylpropanone)-3prenylphloroglucinol 47, caespitate 48 (Popoola et al., 2015b), 2-butanoyl-4-prenylphloroglucinol 49 (Mutanyatta-Comar et al., 2006), 2(2-methylpropanoyl)-4-prenylphloroglucinol 50 (Jakupovic et al.,
1986), 2-(2-methylbutanoyl)-4-prenylphloroglucinol 51 (Bohlmann
and Mahanta, 1979), caespitin 52 (Dekker et al., 1984), 53 (Drawert
and Beier, 1976), 54 (Bohlmann and Mahanta, 1979), 55 (Bohlmann
et al., 1984), 56 (Randriaminahy et al., 1992), and 57 (Jakupovic et al.,
4.3. Benzofurans and phtalides
Benzofuran derivatives are another class of heterocyclic compounds
7
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M. Akaberi, et al.
Table 3
The major constituents and pharmacological activities of the essential oils from Helichrysum spp.
Helichrysum spp.
Major compounds
Activity
Ref.
H. arenarium (L.) Moench.
Spathulenol (36.6%) and β-pinene (12.5%)
_
Beta-caryophyllene, δ-cadinene, octadecane, heneicosane
Antimicrobial
Antibacterial
_
Linalool (1.7%), anethole (3.2%), carvacrol (3.6%) and α-muurolol (1.3%)
Hexadecanoic acid (14.7%), β-caryophyllene (10.6%), α-humulene (7.7%)
Alpha-pinene (38.5%), β-caryophyllene (23.0%), 1,8 cineole (12.0%), Isoborneol
(28.2%), β-caryophyllene (12.9%), δ-cadinene (6.3%), bornyl acetate (6.0%),
carvacrol (37.7%), α-pinene (19.7%) and β-caryophyllene (8.5%)
Beta-pinene (10.3%), 1,8-cineole (24.8%) and α-humulene (10.1%)
1,8-cineole (27.3%)
1, 8-cineole (18%), α-humulene (11.6%) and β-caryophyllene (9.6%)
_
_
_
(Chinou et al., 2004)
(Moghadam et al., 2014)
(Judzentiene and
Butkiene, 2006)
(Czinner et al., 2000)
(Javidnia et al., 2009)
(Azar et al., 2011)
Bera-caryophyllene (46.4%) and α-humulene (10.9%)
(E)-caryophyllene (55.6%)
Alpha-fenchene (35.6%), γ-curcumene (17.7%)
Alpha-fenchene (32.3%), γ-curcumene (19.4%), (E)-β-caryophyllene (14.2%), αcurcumene (2.9%), limonene (2.8%), lavandulyl acetate (2.1%) and α-fenchene
hydrate (1.7%)
(E)-caryophyllene (34.6%)
Selina-5,11-diene (45.3%), δ-3-carene (7.8%), 1,8-cineole (4.2%) and βcaryophyllene (4.9%)
Alpha-cubebene (10.5%), β-caryophyllene (9.4%), azulene-octahydro (7.5%),
caryophyllene oxide (8.2%)
1,8-cineole (47.4%)
1,8-cineole (47.4%), bicyclosesquiphellandrene (5.6%), γ-curcumene (5.6%), αamorphene (5.1%) and bicyclogermacrene (5%)
1,8-cineole (59.7%)
1,8-cineole (51.5%)
(E)-caryophyllene (34.0%)
Gamma-curcumene, α-pinene, β-selinene, α-selinene, and limonene
Neryl acetate (32.65%), γ‐Curcumene (11.64%), Italidione I (7.42%), Limonene
(5.54%), Neryl propionate (4.80%), Italidione II (2.65%), Italidione III (1.92%)
Alpha-trans-bergamotene (10.2%) and β-acoradiene (10.1%) Neryl acetate
(8.1%), β-acoradiene
Nerol (2.8-12.8%) and neryl acetate (5.6-45.9%)
Iso-italicene epoxide (16.8%), β-costol (7.5%) and (Z)-α-trans-bergamotol (4.7%)
Alpha-Cedrene (13.61%), α-curcumene (11.41%), geranyl acetate (10.05%),
limonene (6.07%), nerol (5.04%), neryl acetate (4.91%) and α-pinene (3.78%)
Alpha-cedrene (13.61%), α-curcumene (11.41%), geranyl acetate (10.05%),
limonene (6.07%), nerol (5.04%), neryl acetate (4.91%) and α-pinene (3.78%)
Alpha-pinene (10.2%), α-cedrene (9.6%) aromadendrene (4.4%), β-caryophyllene
(4.2%), and limonene (3.8%), neryl acetate (11.5%), 2-methylcyclohexyl
pentanoate (8.3%), 2-methylcyclohexyl octanoate (4.8%), and geranyl acetate
(4.7%)
Neryl acetate (26.0%), nerol (9.1%), neryl propionate (6.7%), γ-curcumene
(10.8%) and cis-dihydro-occidentalol (4.3%)
Nerol and its esters (acetate and propionate), limonene, and linalool
Neryl acetate (17.6–35.6%), nerol (3.7–14.4%) and eudesmen-5-en-11-ol
(6.4–23.5%)
Nerol (10.7%), neryl acetate (28.9%), neryl propionate (11.4%) and γ-curcumene
(11.4%)
Guaiol (8.9%), nerol (7.0%) and β-caryophyllene (6.0%)
Beta-caryophyllene (30.7%), α-pinene (12.1%), α-humulene (9.8%) and βsesquiphellandrene (6.9%)
Rosifoliol (22.3%), β-caryophyllene (10.1%) and α-humulene (9.0%)
Limonene (74.6%) and α-pinene (12.9%)
Beta-caryophyllene (35.4%) and γ-curcumene (22.3%)
Neryl acetate (18.2%), rosifoliol (5-eudesmen-11-ol, 11.3%) Delta-cadinene
(8.4%) and γ-cadinene (6.7%)
Gamma-gurjunene (11.06%), spathulenol (9.90%), alloaromadendrene (7.53%),
β-caryophyllene (7.10%)
β-pinene (51.6%), limonene (16.9%), α-humulene (5.6 %), β-caryophyllene (4.7
%)
Alpha-pinene (47% and 41%), β-caryophyllene (14% and 5%) and α-curcumene
(4% and 20%)
Alpha-pinene (43.4%), (E, E)-farnesol (16.8%) and α-humulene (14.6%)
Beta-caryophyllene (13.5%), menthone (10.8%), dodecane (9.1%) and menthol
(8.9%)
Fenchene (88.3%)
Cis-α-bisabolene (22.7%), β-caryophyllene (12.6%), β-caryophyllene oxide
(8.8%), β-bisabolene (4.7%) and viridiflorol (3.7%)
Beta-elemene, beta-caryophyllene, geraniol, and camphene
1,8-cineole (11.7%) and β-caryophyllene (29.5%)
_
_
Insecticidal
_
(Baser et al., 2002)
(Cavalli et al., 2001)
(Ramanoelina et al.,
1992)
(Baser et al., 2002)
(Cavalli et al., 2001)
(Benelli et al., 2018)
(Cavalli et al., 2006)
_
_
(Cavalli et al., 2001)
(El-Olemy et al., 2005)
_
(Bagci et al., 2013)
Insecticidal
Cytotoxic, antimalarial,
and antioxidant
_
_
_
_
Antibacterial
(Kasmi et al., 2017)
(Afoulous et al., 2011)
(Cavalli et al., 2001)
(Baser et al., 2002)
(Cavalli et al., 2001)
(Jerković et al., 2016)
(Cui et al., 2015)
_
(Zeljkovic et al., 2015)
_
Phytotoxic
Antimicrobial
(Leonardi et al., 2013)
(Mancini et al., 2011)
(Djihane et al., 2017)
Antimicrobial
(Djihane et al., 2017)
Anti-bacterial and
antifungal
(Mastelic et al., 2005)
_
(Marongiu et al., 2003)
Antifungal
_
(Angioni et al., 2003)
(Usai et al., 2010)
_
(Satta et al., 1999)
_
Antimicrobial
(Tsoukatou et al., 1999)
(Bougatsos et al., 2003)
_
_
Anticancer
(Javidnia et al., 2009)
(Ruberto et al., 2002)
(Pino et al., 2004)
(Ornano et al., 2015)
_
(Elkiran et al., 2013)
Antibacterial and
cytotoxic
_
(Lawal et al., 2015)
(Kuiate et al., 1999)
_
_
(Lwande et al., 1993)
(Firouznia et al., 2007)
_
Antimicrobial
(Öztürk et al., 2014)
(Bougatsos et al., 2003)
_
(Baser et al., 2002)
H. artemisioides Boiss. et Hausskn.
H. aucheri
H. bracteiferum
H. cordifolium
H. faradifani
H. forsskahlii (Gmel) Hilliard et Burt
H. graveolens
H. gymnocephalum
H. hypnoides
H. italicum
H. italicum G. Don ssp.
microphyllum (Willd) Nym
H. italicum ssp. serotinum
H. kraussii
H.
H.
H.
H.
leucocephalum Boiss.
litoreum Guss.
melaleucum Rchb. ex Holl.
microphyllum Cambess. ssp.
tyrrhenicum Bacch.
H. noeanum Boiss.
H. odoratissimum (L.) Less.
H. oocephalum Boiss.
H. plicatum subsp. isauricum
H. rugulosum
H. rupestre
H. rusillonii
_
_
_
(continued on next page)
8
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M. Akaberi, et al.
Table 3 (continued)
Helichrysum spp.
Major compounds
Activity
Ref.
H. selaginifolium
H. splendidum
Beta-pinene (38.2%)
Germacrene D-4-ol (17.08%), germacrene D (9.04%), bicyclogermacrene (8.79%)
and δ-cadinene (8.43%)
Alpha-terpinene (14.9%), β-pinene (10.2%) and 1,8-cineole (8.6%)
Beta-caryophyllene, α-humulene, α-pinene and limonene
Alpha-pinene (28.3%), epi-α-bisabolol (21.9%) and β-caryophyllene (5.5%)
Alpha-pinene (28.3%), epi-α-bisabolol (21.9%) and β-caryophyllene (5.5%)
_
_
(Cavalli et al., 2001)
(Marongiu et al., 2006)
_
Antibacterial
_
_
(Chagonda et al., 1999)
(Roussis et al., 2002)
(Tsoukatou et al., 1999)
(Tsoukatou et al., 1999)
H. stoechas (L.)
H. stoechas ssp. stoechas
69 (Rosa et al., 2007), 70 (Jerković et al., 2016), 71 (Proksch and
Rodriguez, 1983), isocaproylbitalin A 72 (Bohlmann and Zdero, 1970)
and bitalin A β-D-glucopyranoside derivative 73 (D’ Abrosca et al.,
2013), nonanoylbitalin A 74 (Bohlmann and Zdero, 1970), oleoylbitalin
A 75 (Bohlmann and Zdero, 1970), propanoylbitalin A 76 (Bohlmann
and Zdero, 1970), 2,3-dihydro-5,7-dihydroxy-2-isopropenyl-6-(2-methylpropenoyl)benzofuran 77 (Bohlmann et al., 1984), 78, 79 (D’
Abrosca et al., 2013), 80 (Opitz and Hansel, 1971), and 81 (Hänsel
et al., 1980) have been identified in different Helichrysum species. In a
study in 2016, supercritical CO2 extraction of dried immortelle flowers
(H. italicum) yielded tremetone derivatives 12-acetoxytremetone, gnaphaliol 70 as well as bitalin A 66 and 9-acetylgnaphadiol (Jerković
et al., 2016). These compounds can be found as glucosides like β-D-OGlcs of gnaphadiol (Bohlmann et al., 1984; Mari et al., 2014; Rigano
et al., 2014; Rosa et al., 2007; Taglialatela-Scafati et al., 2013).
Phtalide derivatives have also been reported from Helichrysum spp.
Platypterophtalide 82 (Jakupovic et al., 1987b) has been identified
from the roots of H. platypterum (Jakupovic et al., 1987b). The compound 5,7-dihydroxyphtalide 83 (Vrkoč et al., 1973), 5,7-dimethoxyphtalide 84 (Opitz and Hansel, 1971), 7-hydroxy-5-methoxyphthalide
85 (Opitz and Hansel, 1971) and its glucosides 7-O-β-D-glucopyranoside, 7-O-(6-O-malonyl-β-D-glucopyranoside), and 7-O-[β-D-glucopyranosyl -β-D-glucopyranoside] have been reported from H. italicum, H.
arenarium and H. polyphyllum.
4.4. Flavonoids, chalcones, and phenolic acids
These compounds play an important role in the antioxidant and
anti-inflammatory activities reported for this genus and contribute the
major components of the polar fractions from various species (Facino
et al., 1990). Table 2 shows the phenolic compounds isolated so far
from the polar extracts of Helichrysum spp. Flavonoids have been found
as both glycosides and free aglycones as well as dimers, trimers, or
more complex aggregates (Fig. 4). For instance, free aglycones of apigenin, naringenin and kaempferol as well as their glycosides have been
reported from the flower heads of H. plicatum (Bigović et al., 2017).
Some other known flavonoids reported from Helichrysum spp. are
prunin, isosalipurposide, narirutin, naringin, eriodictyol, luteolin, galuteolin, astragalin and quercetin (Bohlmann et al., 1984; Grinev et al.,
2016; Mao et al., 2017). Since Helichrysum spp. are rich in flavonoids,
many new structures have also been reported. Flavonoid-related
structures 86-89 (Popoola et al., 2015a) have been isolated and identified from H. teretifolium (Popoola et al., 2015a). Compounds 90-93
(Morikawa et al., 2009) including four new flavanone and chalcone
glycosides named arenariumosides I, II, III, and IV have been reported
from the methanolic extract from the flowers of H. arenarium (Wang
Fig. 5. Sesquiterpenes from Helichrysum spp.
and possible active constituents present in Helichrysum spp. (Fig. 3).
Tremetone derivatives such as bitalin A 66 (Bohlmann and Zdero, 1970;
Rosa et al., 2007), acetoxytremetone 67, 68, acetoxyhydroxytremetone
9
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M. Akaberi, et al.
Fig. 6. Diterpenes from Helichrysum spp.
et al., 2009).
Moreover, the precursors of flavonoids have been detected as
monomers and dimers; chemical profiling of infusions and decoctions of
H. italicum subsp. picardii by UHPLC-PDA-MS showed chlorogenic and
quinic acids, dicaffeoylquinic-acid isomers and gnaphaliin-A as the
major constituents (Pereira et al., 2017). Cameroonenoside A 94, a new
cinnamic acid glycoside ester has been isolated for the first time from H.
cameroonense (Antoine et al., 2011).
Among various flavonoid constituents of Helichrysum, chalcones are
considered to be one of the most important bioactive compounds (95
and 96) (do Nascimento and Mors, 1972d; Popoola et al., 2015a). For
example, Aljancic et al. (2014) could identify two structurally distinct
chalcone dimers namely tomoroside A 97 and tomoroside B 98 from H.
zivojinii with anti-cancer activities. Similar to these chalcone dimers,
Morikawa et al. (2015) identified three new dimeric dihydrochalcone
glycosides named arenariumosides V-VII 99-101 from a methanol extract of everlasting flowers of H. arenarium L. Moench.
4.5. Terpens and essential oil
Studies on the essential oil profile of plants belonging to Helichrysum
genus constitute the major investigations established on these plants
and revealed that these species produce a complex bouquet of vegetative and floral volatiles. Several essential oil products from Helichrysum
spp. are being sold in the markets for medicinal and non-medicinal
purposes. Table 3 summarizes the main compounds in the essential oil
of different species and their biological activities. The studies have
shown that the essential oil mainly includes monoterpenes and sesquiterpenes and the most reported activity for the oil is antibacterial
and antifungal properties; however, there are a few reports about their
insecticidal and cytotoxic activities.
Helichrysum spp. is a rich source of sesquiterpenes like other members of the plants belonging to Compositae family. The chemical
structures of sesquiterpenes that have been reported to date are depicted in Fig. 5 (102-119). Eudesman sesquiterpenes like eudesm-5-en11-ol 116 from the oil of H. italicum (Bianchini et al., 2004), drimane
10
Industrial Crops & Products 138 (2019) 111471
M. Akaberi, et al.
Fig. 7. Miscellaneous compounds from Helichrysum spp.
derivatives like helinudichromene quinone 140 (Jakupovic et al., 1986),
6-acetyl-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran
141
(Bohlmann and Stöhr, 1980; de Quesada et al., 1972), 6-benzoyl-5,7dihydroxy-2-methyl-2-(4-methyl-3-pentenyl)chroman 142 (Bohlmann
and Zdero, 1980a), 5,7-dihydroxy-6-isobutyryl-2,2-dimethylchroman
143, 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethylchroman 144, 2,2dimethyl-8-(2-methyl-1-oxopropyl)-5,7-dimethylchroman 145, 146
(Jakupovic et al., 1986), 5,7-dihydroxy-2,3-dimethyl-4-chromanone 147
(Mutanyatta-Comar et al., 2006), acetophenones like 4-hydroxy-3-(3methyl-2-butenyl)acetophenone 148 (Appendino et al., 2007a; Sala
et al., 2001), some phenolic derivatives 149 (Bohlmann and Misra,
1984), 150 (Bohlmann and Hoffmann, 1979), 151 (Bohlmann and
Hoffmann, 1979), 152 (Sala et al., 2001), 153 (Jakupovic et al., 1987a),
154 (Bohlmann and Ziesche, 1979), glycosides like everlastosides A-M
155-160 (Morikawa et al., 2009), and other miscellaneous compounds,
such as polyacetylenes, sulphur containing compounds, coumarins like
sesquiterpenes, and guaiane sesquiterpenes are found to be the most
reported ones (Mari et al., 2014).
A large number of diverse diterpenes have been reported from
Helichrysum genus. Most of them belong to abietan, pimaran, and
kaurane diterpenes (120-139) (Fig. 6and Table 6). For example, a diterpene acid related to erythroxydiol A 124 has been isolated from H.
refluxum (Bohlmann et al., 1985). Triterpenes have also been isolated
from some species. A few examples are 3β-hydroxy-28,13-ursanolide,
ursololactone (Lloyd and Fales, 1967), and 3-acetyl-28-oleananoic acid
(Bohlmann et al., 1979b).
4.6. Miscellaneous compounds
The compounds of Helichrysum spp. are not limited to the abovementioned compounds. This genus contains some other compounds belonging to other classes of natural products such as coumarate
11
Compound /Extract
Biological activities
Study design/Result
Ref.
42 and 43
Helinivene A and B
Antioxidant and anti-tyrosinase
(Popoola et al., 2015b)
9
Arzanol
Antioxidant
9, 24, and 4
Arzanol, methylarzanol, and helipyrone
Antioxidant
45
2-(2-methyl-butanoyl)-4-prenylphloroglucinol
Antioxidant
_
Methanol extract of H. foetidum Moench
Antioxidant
_
9, 10
9
Methanol extracts of H. sanguineum (L.) Kostel
Arzanol and arenol
Arzanol
Antioxidant and radical scavenging activity
Anti-tyrosinase
Anti-inflammatory and anti-HIVe
149 and 1
4-hydroxy-3-(3-methyl-2-butenyl)acetophenone and 4hydroxy-3-(2-hydroxy-3-isopentenyl)acetophenone
Anti-inflammatory
9
Arzanol
Anti-inflammatory
9
The aqueous extracts (decoction) from the aerial parts of H.
stoechas, as well as chlorogenic acid, cynarin, and arzanol
Narirutin, naringin, eriodictyol, luteolin, galuteolin, astragalin,
kaempferol
Antiacetylcholinesterase
In vitro, FRAP, ORAC, TEACa and Fe2+-induced microsomal lipid peroxidation
assays Antioxidant activity at IC50 = 5.12 ± 0.90; 3.55 ± 1.92 ppm Antityrosinase activity at IC50 = 35.63 ± 4.67 and 26.72 ± 5.05 ppm
The protective effect against the oxidative modification of lipid components
induced by Cu2+ ions in human low density lipoprotein (LDL) and by tertbutyl hydroperoxide (TBH) in cell membranes Preserved lipoproteins from
oxidative damage at 2 h of oxidation, and showed a remarkable protective
effect on the reduction of polyunsaturated fatty acids and cholesterol levels,
inhibiting the increase of oxidative products
In vitro, autoxidation and iron (EDTAb)-mediated oxidation of linoleic acid at
37 °C, thermal (140 °C) autoxidation of cholesterol Protect linoleic acid
against free radical attack
In vitro, Cu-induced LDL oxidation assay Inhibit LDL oxidation at
concentrations 0.5-10 μM
In vitro, ABTSc assay, DPPHd radical-scavenging, ß-carotene/linoleic acid
assay, scavenging of hydrogen peroxide test, superoxide anion scavenging test
and hypochlorous acid scavenging test
DPPH assay, IC50 = 12.90 ppm
IC50 35.63 and 26.72 ppm, respectively
Inhibit HIV-1 replication in T cells and the release of pro-inflammatory
cytokines in stimulated primary monocytes
The chronic inflammation induced by 12-O-tetradecanoylphorbol 13-acetate,
the phospholipase A(2)-induced mouse paw oedema test, the carrageenaninduced mouse paw oedema test, and the writhing induced by acetic acid in
the mouse Inhibit oedema formation, showing a similar profile to that
obtained with cyproheptadine, inhibitor of both cyclooxygenase and 5lipoxygenase
In vivo, inhibit 5-lipoxygenase (EC 7.13.11.34) activity and related
leukotriene formation in neutrophils, as well as the activity of cyclooxygenase
(COX)-1 (EC1.14.99.1) and the formation of COX-2-derived prostaglandin
(PG)E2 in vitro (IC50 = 2.3–9 mM), inhibits microsomal PGE2 synthase
(mPGES)-1 (EC 5.3.99.3, IC50 = 0.4 mM) rather than COX-2, block COX-2/
mPGES-1-mediated PGE2 biosynthesis in lipopolysaccharide-stimulated
human monocytes and human whole blood, suppress the inflammatory
response of the carrageenan-induced pleurisy in rats (3.6 ppm, i.p.), with
significantly reduced levels of PGE2 in the pleural exudates
In vitro Flowers and stems/leaves extracts inhibited antiacetylcholinesterase
with IC50 values of 260.7 and 654.8 ppm
AS model using thoracic aortas vascular ring Inhibit the expression of VEGFf,
CRPg, JNK2h, p38 and NO (nitric oxide) at different level, reduce the
expression of CRP, inhibit the kinases activity of JNK2 and p38, and then
suppress the mitogen-activated protein kinase (MAPK) pathway, which
resulted in the decrease of NO synthesis, VEGF expression and endothelial
adhesion factor expression
Dipeptidyl peptidase-IV inhibitory activity in vivo Inhibit the increase in blood
glucose elevation in sucrose-loaded mice (500 ppm p.o.), inhibit the
enzymatic activity against dipeptidyl peptidase-IV (IC50 = 41.2 ppm)
In vitro Inhibit digestive α-amylase and α-glucosidase activities and SGLT1mediated methylglucoside uptake in Caco-2 cells in the presence of Na(+),
decreased blood glucose levels after an oral maltose tolerance test, reduced
postprandial glucose levels after the oral starch tolerance test, improve
hyperinsulinemia and HOMAi index in a dietary model of insulin resistance in
rats
12
Compound No.
_
Anti-atherosclerotic
Aureusidin 6-O-β-D-glucopyranoside, chalconaringenin 2´-Oβ-D-glucopyranoside
Anti-diabetic
_
H. italicum and grapefruit (Citrus × paradisi) extracts
Anti-diabetic
(Rosa et al., 2011)
(Rosa et al., 2007)
(Mutanyatta-Comar
et al., 2006)
(Tirillini et al., 2013)
(Albayrak et al., 2008)
(Popoola et al., 2015b)
(Appendino et al.,
2007b)
(A. Sala et al., 2003)
(J. Bauer et al., 2011)
(Silva et al., 2017)
(Mao et al., 2017)
(Morikawa et al.,
2015)
(De La Garza et al.,
2013)
(continued on next page)
Industrial Crops & Products 138 (2019) 111471
85, 92
M. Akaberi, et al.
Table 4
Biological activities reported from the compounds of Helichrysum spp.
Compound No.
Compound /Extract
Biological activities
Study design/Result
Ref.
_
H. teretifolium total extract and isolated flavonoids 4'methoxyquercetin and quercetin
Anti-aging, antioxidant and moderate antityrosinase and anti-elastase
(Popoola et al., 2015a)
_
Ethanol extract of H. plicatum flowers
Anti-cancer
97 and 98
Naringenin 7-O-β-D-glucopyranoside, apigenin 7-O-βDglucopyranoside, apigenin 7-O-gentiobioside, and apigenin
7,4-di-O-β-D-glucopyranoside
Tomoroside A and B
Compounds quercetin and 4'-methoxyquercetin demonstrated the highest
inhibitory activities on Fe2+-induced lipid peroxidation (IC50 = 2.931;
6.449 ppm); tyrosinase (8.092; 27.573) and elastase (43.342; 86.548)
In vitro; isolated rat ileum Inhibit the spontaneous ileum contractions and
contractions induced by acetylcholine, histamine, barium and potassium ions
Inhibitory activity on tumor necrosis factor-α (1 ppb)-induced cytotoxicity on
cancerous cell lines
(Aljančić et al., 2014)
_
H. plicatum DC. subsp. plicatum ethanol extract
Nephro protective
_
The methanol extract of H. graveolens flowers as well as
apigenin
Wound healing
H. plicatum DC. subsp. plicatum extract
Anti urolithiasis
Methanol extract of H. stoechas
Antiproliferative
Dichloromethane extract of H. oocephalum
Anti-protozoal
In vitro, NCI-H460 and NCI-H460/R cells 97 inhibited topo IIα and hif-1α
expression and stimulated doxorubicin anticancer effect, while 98 increased
the expression of hif-1α, probably acting as antioxidant and redox status
modulator
In vivo (rats); 100 ppm; gentamicin-induced nephrotoxicity Decreased serum
blood urea nitrogen, and creatinin, liver and kidney oxidant markers and
tubular necrosis as well as by an increase in antioxidant enzymes, increased
liver and kidney tissue malondialdehyde levels
In vivo; the linear incision and the circular excision wound models Possessed
significant anti-inflammatory, antioxidant, anti-hyaluronidase and anticollagenase activities
In vivo (rats); 125, 250, and 500 ppm; 1% ethylene glycol and 1% ammonium
chloride-induced urolithiasis Decreased levels of both serum and urine
biochemical parameters, Urine CaOx level, improved histopathological
parameters
In vitro (HeLa cells); MTT assay; 0.008, 0.016, 0.031, 0.063,0.125, 0.250,
0.500 and 1.000 mg/mL; non-treated cells (control) Dose-dependent
antiproliferative effects at concentrations over 0.06 mg/mL with an IC50 of
0.15 mg/mL
In vitro; Leishmania donovani (MHOM-ET-67/L82) axenically grown
amastigotes; 100 to 0.001 ppm 34 with IC50 1.79 ± 0.17 μM showed the
highest activity
Anti-cancer
13
11-14, 20-23, 3335, 58-65
a
b
c
d
e
f
g
h
i
M. Akaberi, et al.
Table 4 (continued)
(Bigovic et al., 2010)
(Wang et al., 2009)
(Apaydin Yildirim
et al., 2017)
(Süntar et al., 2013)
(Les et al., 2017)
(Akaberi et al., 2019)
the ferric reducing ability of plasma; the oxygen radical absorbance capacity; trolox equivalent antioxidant capacity.
ethylenediaminetetraacetic acid.
2,2′-azinobis-3-ethylbenzothiazoline-6-sulphonic acid.
1,1-diphenyl-2-picrylhydrazyl.
human immunodeficiency viruses.
vascular endothelial growth factor.
c-reactive protein.
c-Jun N-terminal kinases.
homeostatic model assessment.
Industrial Crops & Products 138 (2019) 111471
Industrial Crops & Products 138 (2019) 111471
(Appendino et al., 2007a)
(Albayrak et al., 2008)
(Albayrak et al., 2008)
(Albayrak et al., 2008)
(Turker and Usta, 2008)
(Djihane et al., 2017)
5. Pharmacology
100 to 400 ppm
_
_
_
_
6.325 ppm, 0.79 ppm, 12.65
ppm
_
_
_
_
_
A variety of pharmacological activities have been reported for the
bioactive compounds from Helichrysum spp., particularly arzanol as a
prenylated heterodimeric phloroglucinyl α-pyrone derivative (Table 4).
Arzanol has been reported to possess anti-inflammatory, anti-HIV, antioxidant, antibiotic, anti-cancer and antiviral activities (Rosa et al.,
2017). Arzanol inhibits NFκB activation, HIV replication in T cells, release of proinflammatory mediators like IL-1β, IL-6, IL-8 and TNF-α,
and biosynthesis of PGE2 by inhibiting the mPGES-1 enzyme
(Kothavade et al., 2013) (Table 4).
Although the activities for different extracts and pure compounds
from Helichrysum spp. are diverse, the most cited ones are related to its
antibacterial and antiviral properties. Table 5 shows the studied species
from everlasting flowers with antimicrobial activities. In a screening
study, Albayrak et al. (2010) investigated the antimicrobial activities of
the phenol-rich extracts of some Turkish Helichrysum spp. including, H.
arenarium (L.) Moench subsp. aucheri (Boiss), H. armenium DC. subsp.
armenium, H. artvinense Davis & Kupicha, H. chionophilum Boiss. & Bal,
H. compactum Boiss, H. goulandriorum E. Georgiadou, H. graveolens
(Bieb.) Sweet, H. heywoodianum Davis, H. kitianum Yıldız, H. noeanum
Boiss., H. orientale (L.) DC. and H. pallasii (Sprengel) Ledeb (Albayrak
et al., 2010). All extracts showed strong antimicrobial activity against
microorganisms including thirteen bacteria and two yeasts in the agar
diffusion test (Albayrak et al., 2010). Moreover, the anti-microbial activity of the ethanol extract of H. plicatum has been investigated against
various bacteria and fungi as well as the yeast Candida albicans using
the microdilution method (Bigović et al., 2017). Gram-positive bacteria
with MIC values of 0.02 mg/mL were more sensitive to the plant extract
compared with Gram-negative ones. Moreover, the sensitivity of fungi
was more than bacteria (Bigović et al., 2017). Not only the extracts
showed strong antimicrobial activities, but also the isolated compounds
exhibited pharmacological effects. For example, phloroglucinol derivatives 17-19 showed antifungal activities against Cladosporium herbarum (Tomás-Lorente et al., 1989). In another study, both methanol
extract and the phenolic compounds from H. arenarium (L.) Moench
subsp. arenarium inflorescences showed antibacterial activity against
lower respiratory tract pathogens (standard strains and clinical isolates)
(Gradinaru et al., 2014). The extract exhibited similar antibacterial
effects against methicillin-resistant S. aureus and penicillin-resistant S.
pneumoniae clinical isolates (MIC = 2.5 mg/mL), displaying a higher
activity against ampicillin-resistant Moraxella catarrhalis isolate
(MIC = 0.15 mg/mL). In addition, combination of the extract with ciprofloxacin increased the anti-bacterial activity (Gradinaru et al.,
2014).
In addition, most of the studies on this genus have investigated the
essential oil activity and composition. Thus, the majority of pharmacological studies reported for these plants, mostly investigating antimicrobial activities, are related to the essential oils (Table 3).
Diethyl ether extract
Methanol extract
Methanol extract
Methanol extract
_
Essential oil
6. Conclusion
long terminal repeats.
Everlasting flowers (Helichrysum spp.) have been shown to be an
interesting source of bioactive secondary metabolites with diverse
properties, potentially capable of treating microbial diseases. However,
more studies must be established to investigate the intact and unexplored species to find out their potential activities and the responsible
bioactive components. Moreover, supplementary studies such as clinical trials are necessary for those species and properties that are already
investigated and suggested by traditional and modern medicine.
a
H.
H.
H.
H.
H.
H.
Herpes Simplex Virus
Klebsiella pneumoniae
Staphylococcus aureus, Proteus vulgaris
S. aureus
Streptococcus pyogenes, S. aureus, S. epidermidis
Candida albicans, Enterococcus cereus, and
Saccharomyces cerevisiae
25 ppm and 5 μM
H. italicum
HIV-1-LTRa
Phloroglucinol and acetophenone
derivatives
Arzanol
esculetin, scopoletin, and isoscopoletin (Fig. 7) (Karasartov et al., 1992;
Morikawa et al., 2009; Wang et al., 2009).
italicum
pamphylicum
sanguineum
chasmolycicum
plicatum
italicum
Inhibition of the TNFα-induced HIV-1-LTR
transactivation in a T cell line
(Tomás-Barberán et al.,
1990)
(Appendino et al., 2007a)
(Nostro et al., 2000)
(Tundis et al., 2005)
125 ppm
50 ppm
Diethyl ether extract
Methanol extract
H.
H.
H.
H.
Bacillus subtilis
Micrococcus luteus
Staphylococcus aureus
Penicillium
italicum
italicum
italicum
italicum
MIC
Extract/compound
Species
Microorganism
Table 5
Helichrysum spp. with reported antimicrobial activities.
Description
Ref.
M. Akaberi, et al.
14
Industrial Crops & Products 138 (2019) 111471
M. Akaberi, et al.
Table 6
The phytochemicals reported from Helichrysum spp.
Compound
Pyrones
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Plant
Name
Ref.
H. italicum
H. italicum
H. italicum
H. italicum and H.
stoechas
H. arenarium and H.
stoechas
H. arenarium and H.
stoechas
H. auriceps
H. cephaloideum
H. italicum ssp.
microphyllum
H. italicum ssp.
microphyllum
H. oocephalum
Helichrysum spp.
Micropyrone
Yangonin O12-De-Me, 12-O-[3-hydroxy-3-methylglutaroyl-(6)-β-D-glucopyranoside
Yangonin O12-De-Me, 12-O-(6-O-malonyl-β-D-glucopyranoside)
Helipyrone A
(Appendino et al., 2007a)
(D’ Abrosca et al., 2013)
(D’ Abrosca et al., 2013)
(Opitz and Hänsel, 1970)
Helipyrone B (norhelipyrone)
(Rios et al., 1991)
Helipyrone C
(Rios et al., 1991)
23-methylauricepyrone
Norauricepyrone
Arzanol
(Bohlmann and Zdero, 1980b)
(Jakupovic et al., 1986)
(Appendino et al., 2007a)
Arenol
(Appendino et al., 2007a)
23-Methyl-6-O-desmethylauricepyrone
2H-Pyran-2-one, 6-ethyl-4-hydroxy-5-methyl-3-[[2,4,6-trihydroxy-3-(3-methyl-2buten-1-yl)-5-(2-methyl-1-oxopropyl)phenyl]methyl]Arenol B
Arenol C
Heliarzanol
(Akaberi et al., 2019)
(Jakupovic et al., 1986)
Auricepyrone
3-[3-Acetyl-5-(3,7-dimethyl-2,6-octadienyl)-2,4,6-trihydroxybenzyl]-4-hydroxy-5,6dimethyl-H-pyran-2-one
3-[3-Acetyl-5-(3,7-dimethyl-2,6-octadienyl)-2,4,6-trihydroxybenzyl]-4-hydroxy-5methyl-6-ethyl-H-pyran-2-one
3-[3-Acetyl-5-(3,7-dimethyl-2,6-octadienyl)-2,4,6-trihydroxybenzyl]-4-hydroxy-5methyl-6-propyl-H-pyran-2-one
Achyroclinopyrone A
Achyroclinopyrone B
16Z/E-Achyroclinopyrone C
16Z/E-Achyroclinopyrone D
Methyl arzanol
(Bohlmann and Zdero, 1980b)
(Tomás-Barberán et al., 1990; Tomás-Lorente
et al., 1989)
(Tomás-Barberán et al., 1990; Tomás-Lorente
et al., 1989)
(Tomás-Barberán et al., 1990; Tomás-Lorente
et al., 1989)
(Akaberi et al., 2019)
(Akaberi et al., 2019)
(Akaberi et al., 2019)
(Akaberi et al., 2019)
(Rosa et al., 2007)
Italidipyrone
Italipyrone
20-prenylitalipyrone
Plicatipyrone
Isobutyrylhelichromenopyrone
2-methylbutyrylhelichromenopyrone
Helicerastripyrone
Helicepyrone
Cycloarzanol
Helicyclol
Lepidissipyrone
8-prenyllepidissipyrone
Helitalone A
Helitalone B
(Hänsel et al., 1980)
(Hänsel et al., 1980; Rios et al., 1991)
(Hänsel et al., 1980)
(Hänsel et al., 1980)
(Jakupovic et al., 1986)
(Jakupovic et al., 1986)
(Bohlmann et al., 1984)
(Akaberi et al., 2019)
(Akaberi et al., 2019)
(Akaberi et al., 2019)
(Jakupovic et al., 1989b)
(Jakupovic et al., 1989b)
(Werner et al., 2019)
(Werner et al., 2019)
Helinudifolin
1,1'-[(6-Methylheptylidene)bis(3,4-dihydro-5,7-dihydroxy-2,2-dimethyl-2H-1benzopyran-6,6'-diyl)]bis[2-methyl-1-propanone]
Helinivene A
Helinivene B
1-(butanone)-3-prenyl-phloroglucinol
1-(2-methylbutanone)-3-prenyl-phloroglucinol
1-butanone-3-(3-methylbut-2-enylacetate)-phloroglucinol
1-(2-methylpropanone)-3-prenylphloroglucinol
Caespitate
2-butanoyl-4-prenylphloroglucinol
2-(2-methylpropanoyl)-4-prenylphloroglucinol
2-methyl-1-[2,4,6-trihydroxy-3-(3-methyl-2-butenyl)-1-butanone(Appendino et al.,
2007a)
(Jakupovic et al., 1986)
(Jakupovic et al., 1986)
16
17
H. oocephalum
H. oocephalum
H. italicum ssp.
microphyllum
H. auriceps
H. decumbens
18
H. decumbens
19
H. decumbens
20
21
22
23
24
H.oocephalum
H.oocephalum
H.oocephalum
H.oocephalum
H. italicum ssp.
Microphyllum
25
H. italicum
27
H. stoechas
28
H. stoechas
29
H. plicatum
30
H. mixtum
31
H. mixtum
32
Helichrysum spp.
33
H. oocephalum
34
H. oocephalum
35
H. oocephalum
36
H. lepidissimum
37
H. lepidissimum
38
H. italicum
39
H. italicum
Phloroglucinols
40
H. nudifolium
41
H. platypterum
42
43
44
45
46
47
48
49
50
51
H. niveum
H. niveum
H. niveum
H. niveum
H. niveum
H. niveum
H. niveum
H. paronychioides
Helichrysum spp.
Helichrysum spp.
52
53
54
55
56
57
H. caespititium
Helichrysum spp.
H. gymnocomum
Helichrysum spp.
H. aphelexioides
H. monticola
Caespitin
2-methyl-1-[2,4,6-trihydroxy-3-(3-methyl-2-butenyl)phenyl]-1-propanone
2-methyl-1-[2,4,6-trihydroxy-3-(2-hydroxy-3-methyl-3-butenyl)phenyl]-1-propanone
5,7-dihydroxy-2-isopropyl-4H-1-benzopyran-4-one
5'-deprenylhemihumulone
3-(3,4-dihydroxyphenyl)-1-[3-(3,7-dimethyl-2,6-octadienyl)-2,4-dihydroxy-6methoxyphenyl]-1-propanone.3'-geranyl-2',3,4,4'-tetrahydroxy-6'methoxydihydrochalcone
(Akaberi et al., 2019)
(Akaberi et al., 2019)
(Taglialatela-Scafati et al., 2013)
(Popoola et al., 2015b)
(Popoola et al., 2015b)
(Popoola et al., 2015b)
(Popoola et al., 2015b)
(Popoola et al., 2015b)
(Popoola et al., 2015b)
(Popoola et al., 2015b)
(Mutanyatta-Comar et al., 2006)
(Jakupovic et al., 1986)
(Bohlmann and Mahanta, 1979; Bohlmann
and Suwita, 1979b; Bohlmann and Zdero,
1979)
(Dekker et al., 1984)
(Drawert and Beier, 1976)
(Bohlmann and Mahanta, 1979)
(Bohlmann et al., 1984)
(Randriaminahy et al., 1992)
(Jakupovic et al., 1989b)
(continued on next page)
15
Industrial Crops & Products 138 (2019) 111471
M. Akaberi, et al.
Table 6 (continued)
Compound
Plant
58-65
H. oocephalum
Benzofurans
66
H. italicum and H.
stoechas
67
H. italicum subsp.
microphyllum
68
H. italicum subsp.
microphyllum
69
H. italicum subsp.
microphyllum
70
H. italicum
71
H. stoechas
72
H. italicum
73
H. italicum
74
H. italicum ssp.
microphyllum
75
H. italicum ssp.
microphyllum
76
H. italicum ssp.
microphyllum
77
Helichrysum spp.
78
79
80
81
82
83
84
85
H. italicum
H. italicum
H. italicum
H. bracteatum
H. platypterum
H. arenarium
H. arenarium
H. arenarium and H.
polyphyllum
Flavonoids and Chalcones
86
H. tereifolium
87
H. tereifolium
88
H. tereifolium
89
H. tereifolium
90
H. arenarium
91
H. arenarium
92
H. arenarium
93
H. arenarium
94
H. cameroonense
95
H. rugulosum
96
H. teretifolium
97
H. zivojinii
98
H. zivojinii
99
H. arenarium
100
H. arenarium
101
H. arenarium
Sesquiterpenes
102
H. bilobum ssp. bilobum
103
H. albirosulatum
104
H. splendidum
105
H. dasyanthum
106
H. splendidum
107
H. splendidum
108
H. nudifolium
109
H. nudifolium
110
H. nudifolium
111
H. italicum
112
H. chinosphaerum
113
H. chionosphaerum
114
H. dasyanthum
115
H. italicum
116
H. arenarium
117
H. dasyanthum
118
H. petiolare
119
H. ambiguum
Diterpenes
120
H. refluxum
121
H. chionosphaerum
122
123
124
125
H.
H.
H.
H.
formosissinum
chionosphaerum
dendroideum
dendroideum
Name
Ref.
Helispiroketals A-H
(Akaberi et al., 2019)
Bitalin A (R)-form
(Bohlmann and Zdero, 1970; Rosa et al., 2007)
Acetoxytremetone
(Rosa et al., 2007)
Diacetyl-2,3-dihydro-3-hydroxy-2-[1-(hydroxymethyl)ethenyl]benzofuran
(Rosa et al., 2007)
Acetoxyhydroxytremetone
(Rosa et al., 2007)
Gnaphaliol
6-methyleuparin
Isocaproylbitalin A
Isobenzofuranone
Nonanoylbitalin A
(Jerković et al., 2016)
(Proksch and Rodriguez, 1983)
(Bohlmann and Zdero, 1970)
(D’ Abrosca et al., 2013)
(Bohlmann and Zdero, 1970)
Oleoylbitalin A
(Bohlmann and Zdero, 1970)
Propanoylbitalin A
(Bohlmann and Zdero, 1970)
2,3-dihydro-5,7-dihydroxy-2-isopropenyl-6-(2-methylpropenoyl)benzofuran [(R)form]
3-hydroxydihydrobenzofuran glycosides
3-hydroxydihydrobenzofuran glycosides
10-acetoxytoxol
bractein
Platypterophthalide
5,7-dihydroxy-1(3 H)-isobenzofuranone
5,7-dimethoxy-1(3 H)-isobenzofuranone
7-hydroxy-5-methoxy-1(3 H)-isobenzofuranone. 7-Hydroxy-5-methoxyphthalide
(Bohlmann et al., 1984)
(D’ Abrosca et al., 2013)
(D’ Abrosca et al., 2013)
(Hänsel et al., 1980)
(Farkas and Pallos, 1965; Honda et al., 1991)
(Jakupovic et al., 1987b)
(Vrkoč et al., 1973)
(Opitz and Hansel, 1971)
(Opitz and Hansel, 1971)
Isoglabranin
4'-methoxyquercetin
4'-methoxykaempferol
mosloflavone
Arenariumoside I
Arenariumoside II
Arenariumoside III
Arenariumoside IV
Cameroonenoside A
Derricidin
Heliteretifolin
Tomoroside A
Tomoroside B
Arenariumoside V
Arenariumoside VI
Arenariumoside VII
(Popoola et al., 2015a)
(Popoola et al., 2015a)
(Popoola et al., 2015a)
(Popoola et al., 2015a)
(Morikawa et al., 2009)
(Morikawa et al., 2009)
(Morikawa et al., 2009)
(Morikawa et al., 2009)
(Antoine et al., 2011)
(do Nascimento and Mors, 1972d)
(Popoola et al., 2015a)
(Aljančić et al., 2014)
(Aljančić et al., 2014)
(Morikawa et al., 2015)
(Morikawa et al., 2015)
(Morikawa et al., 2015)
4-Ambiguen-1-ol
10-hydroxy-3-aromadendranone
4-hydroxy-10(14),11α(13-dihydro)-guaiadien-12,8-olide
4-hydroxy-1(10),11(13)-guaiadien-12,8-olide
Helisplendiolide
4-hydroxy-9-guaien-12,8-olide
8α-hydroxy-α-gurjunene
8α-acetoxy-α-gurjunene
2-isocomanone
Italicene
1(10),4-bicyclogermacradien-13-oic acid
Humulatrien
4,10(14)-cadinadiene-1,3,9-triol
Italicene ether
5-selinen-11-ol
3,9-dihydroxy-δ-cadinene
1,9-cadinadien-3-one [(4α,6α,7α)-form]
1,3,5,7,9-cadinapentaen-14-al
(Jakupovic et al., 1989a)
(Bohlmann et al., 1978)
(Jakupovic et al., 1989b)
(Jakupovic et al., 1989b)
(Bohlmann and Suwita, 1979a)
(Jakupovic et al., 1989b)
(Bohlmann et al., 1978)
(Bohlmann et al., 1978)
(Jakupovic et al., 1986)
(Honda et al., 1991)
(Jakupovic et al., 1989b)
(Bohlmann et al., 1980)
(Jakupovic et al., 1989b)
(Cool et al., 1994)
(Morikawa et al., 2015)
(Jakupovic et al., 1989b)
(Jakupovic et al., 1989b)
(Jakupovic et al., 1989a)
3,15-erythroxyladien-18-oic acid
7,13-abietadiene (ent-5α-form)
(Bohlmann et al., 1985)
(Bohlmann et al., 1980; Jakupovic et al.,
1990)
(Jakupovic et al., 1990)
(Bohlmann et al., 1980)
(Lloyd et al., 1978)
(Lloyd and Fales, 1967)
7,13-abietadien-12β-ol
Atisirenic acid
Erythroxydiol A
15-stachene-3,17-diol
(continued on next page)
16
Industrial Crops & Products 138 (2019) 111471
M. Akaberi, et al.
Table 6 (continued)
Compound
Plant
Name
Ref.
126
H. dendroideum
127
H. nudifolium
128
H. chionosphaerum
129
H. chionosphaerum
130
H. aureum and H. cooperi
131
H. fulvum
132
H. fulvum
133
H. chionosphaerum
134
H. chionosphaerum
135
H. davenportii
136
H. foetidum
137
Helichrysum spp.
138
H. dendroideum
139
H. dendroideum
Miscellaneous compounds
140
H. nudifolium
141
Helichrysum spp.
15-stachene-3,19-diol
13(16),14-gnaphaladien-8α-ol
10(20),16-grayanotoxadien-19-oic acid [(1β,5β,9β)-form]
Acetyl-16-kauren-19-oic acid
11-acetyl-16-kauren-19-oic acid
11-hydroxy-19-helvifulvanoic acid (ent-11β)-form
11-acetoxy-19-helvifulvanoic acid
19-helvifulvanol [ent-form]
Helifulvanic acid
12β-hydroxy-15-kauren-19-oic acid
15α-hyroxy-16-kauren-19-oic acid
Grandiflorenic acid (ent-form)
15-kaurene-17,19-diol (ent-form)
16-kaurene-3β,19-diol
(Lloyd and Fales, 1967)
(Jakupovic et al., 1986)
(Jakupovic et al., 1989b)
(Jakupovic et al., 1989b)
(Bohlmann et al., 1978)
(Bohlmann et al., 1979a)
(Bohlmann et al., 1979a)
(Bohlmann et al., 1980)
(Bohlmann et al., 1980)
(Jakupovic et al., 1989a)
(Barrero et al., 1998)
(Herz and Kulanthaivel, 1984)
(Lloyd and Fales, 1967)
(Lloyd and Fales, 1967)
Helinudichromene quinone
6-acetyl-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran
142
143
144
145
146
147
148
149
150
151
152
153
154
155-160
6-benzoyl-5,7-dihydroxy-2-methyl-2-(4-methyl-3-pentenyl)chroman
5,7-dihydroxy-6-isobutyryl-2,2-dimethylchroman
5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethylchroman
2,2-dimethyl-8-(2-methyl-1-oxopropyl)-5,7-dimethylchroman
5-hydroxy-8-isobutyryl-2,2-dimethyl-7-methoxychroman
5,7-dihydroxy-2R,3R-dimethyl-4-chromanone
4-hydroxy-3-(3-methyl-2-butenyl)acetophenone
Spinoflavone B
Dihydroamorphastilbol
2,4-dihydroxy-6-(2-phenylethyl)-3-prenylbenzoic acid
3-(2-hydroxyethyl)acetophenone 4-O-β-D-glucopyranoside
Acuminatolide
Aureonitol, (-)-form
Everlastoside F-K
(Jakupovic et al., 1986)
(Bohlmann and Stöhr, 1980; de Quesada et al.,
1972)
(Bohlmann and Zdero, 1980a)
(Jakupovic et al., 1986)
(Jakupovic et al., 1986)
(Jakupovic et al., 1986)
(Jakupovic et al., 1986)
(Mutanyatta-Comar et al., 2006)
(Appendino et al., 2007a; Sala et al., 2001)
(Bohlmann and Misra, 1984)
(Bohlmann and Hoffmann, 1979)
(Bohlmann and Hoffmann, 1979)
(Sala et al., 2001)
(Jakupovic et al., 1987a)
(Bohlmann and Ziesche, 1979)
(Morikawa et al., 2009)
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
monticola
platypterum
platypterum
platypterum
platypterum
paronychioides
italicum
rugulosum
umbraculigerum
umbraculigerum,
italicum
acuminatum
aureonitens
arenarium
Table 7
Scientific names of the studied plant taxa.
No.
Plant name
No.
Plant name
1
H. acuminatum (Link) DC.
54
2
H. adenocarpum DC.
55
3
H. albirosulatum Killick
56
4
5
6
7
8
9
H. ambiguum (Pers.) C.Presl
H. amorginum Boiss. & Orph.
H. aphelexioides DC.
H. appendiculatum Less.
H. arenarium (L.) Moench Basionym: Gnaphalium arenarium L.
H. arenarium subsp. aucheri (Boiss) P.H.Davis & Kupicha Basionym:
Helichrysum aucheri Boiss.
H. argyrophyllum DC.
H. armenium DC. subsp. armenium
H. artemisioides Boiss. & Hausskn.
H. athrixiifolium O.Hoffm.
H. artvinense Davis & Kupicha
H. aureum (Houtt.) Merr. Basionym: Gnaphalium aureum Houtt.
H. auriceps Hilliard
H. auronitens Sch.Bip.
H. bilobum subsp. bilobum
H. bracteatum (Vent.) Willd. Basionym: Xeranthemum bracteatum Vent.
H. bracteiferum (DC.) Humbert Basionym: Stenocline bracteifera DC.
H. caespititium (DC.) Sond. Basionym: Helichrysum lineare var. caespititium DC.
H. callicomum Harv.
H. calophalum Klatt
H. cameroonense Hutch. & Dalziel
H. cephaloideum DC.
H. chasmolycicum P.H.Davis
H. chionophilum Boiss. & Balansa
H. chionosphaerum DC.
H. cochleariforme DC.
H. compactum Boiss.
57
58
59
60
61
62
H. italicum subsp. microphyllum (Willd.) Nym.Basionym: Gnaphalium microphyllum
Willd.
H. italicum subsp. picardii (Boiss. & Reut.) Franco Basionym: Helichrysum picardii
Boiss. & Reut.
H. italicum subsp. serotinum (Boiss.) P.Fourn. Basionym: Helichrysum serotinum var.
occidentale Boiss.
H. kitianum Yıldız
H. kraussii Sch. Bip
H. lepidissimum S.Moore
H. leucocephalum Ausfeld
H. litoreum Guss.
H. longifolium DC.
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
maracandicum Popov
mechowianum Klatt
melaleucum Rchb.
miconiifolium DC.
microphyllum (Willd.) Cambess. subsp. tyrrhenicum Bacch. & al.
mixtum (Kuntze) Moeser Basionym: Gnaphalium mixtum Kuntze
monticola Hilliard
niveum Graham
noeanum Boiss.
nudifolium (L.) Less. Basionym: Gnaphalium nudifolium L.
nudifolium var. leiopodium (DC.) Moeser Basionym: Helichrysum leiopodium DC.
obconicum DC.
odoratissimum (L.) Sweet Basionym: Gnaphalium odoratissimum L.
oocephalum Boiss.
orientale Gaertn.
pallasii Ledeb.
pamphylicum P.H.Davis & Kupicha
panduratum O.Hoffm. ex De Wild. & T.Durand.
pandurifolium Schrank
paronychioides DC.
patulum (L.) D.Don Basionym: Gnaphalium patulum L.
(continued on next page)
17
Industrial Crops & Products 138 (2019) 111471
M. Akaberi, et al.
Table 7 (continued)
No.
Plant name
31
32
33
34
35
36
37
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
H.
39
41
42
43
44
45
46
47
48
49
50
51
52
53
cooperi Harv.
cordifolium DC.
crispum (L.) D. Don [Illegitimate]
dasyanthum (Willd.) Sweet
davenportii F.Muell.
decumbens Cambess.
dendroideum N.A.Wakef.
devium J.Y.Johnson
dregeanum Sond. & Harv.
ecklonis Sond.
faradifani Scott Elliot
foetidum (L.) Cass. Basionym: Gnaphalium foetidum L.
formosissimum Sch.Bip.
forsskahlii Hilliard & B.L.Burtt
fulgidum Willd
fulvum N.E.Br.
goulandriorum Georgiadou
graveolens (M.Bieb.) Sweet Basionym: Gnaphalium graveolens M.Bieb.
gymnocephalum (DC.) Humbert Basionym: Stenocline gymnocephala DC.
gymnocomum DC.
heywoodianum Davis
hypnoides (DC.) Viguier & Humbert Basionym: Aphelexis hypnoides DC.
italicum (Roth) Don Basionym: Gnaphalium italicum Roth
No.
Plant name
84
85
86
87
88
89
90
H. pedunculatum Hilliard & B.L.Burtt
H. petiolare Hilliard & B.L.Burtt
H. platypterum DC.
H. plicatum DC.
H. plicatum subsp. isauricum Parolly
H. plicatum subsp. plicatum
H. polyphyllum Ledeb.
H. psilolepis Harv.
H. reflexum N.E.Br.
H. rugulusum Less.
H. rupestre Guss. ex Nyman
H. rusillonii Hochr.
H. sanguineum (L.) Kostel. Basionym: Gnaphalium sanguineum L.
H. selaginifolium (DC.) Viguier & Humbert Basionym: Gnaphalium selaginifolium DC.
Helichrysum setosum Harv.
H. splendidum (Thunb.) Less. Basionym: Gnaphalium splendidum Thunb.
H. stoechas Moench
H. stoechas subsp. stoechas
H.subglomeratum Less.
H. tenax M.D. Hend var. tenax
H. teretifolium (L.) D.Don Basionym: Gnaphalium teretifolium L.
H. tomentosulum (Klatt) Merxm. Basionym: Stenocline tomentosula Klatt
H. zivojini Černjavski & Soska
92
94
95
96
97
98
99
100
101
102
103
104
105
106
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