CHEMISTRY & BIODIVERSITY – Vol.

7 (2010) 327

REVIEW

Phytochemicals and Biological Activities of Pulicaria Species

by Lei-Lei Liu a ), Jun-Li Yang a ), and Yan-Ping Shi* a ) b )
a
) State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000,
P. R. China
b
) Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, Lanzhou 730000, P. R. China
(phone: þ 86-931-4968208; fax: þ 86-931-8277088; e-mail: shiyp@lzb.ac.cn)

Contents
1. Introduction
2. Chemical Constituents
2.1. Phenolic Derivatives
2.2. Monoterpenes
2.3. Sesquiterpenoids
2.3.1. Germacranes
2.3.2. Xanthanes
2.3.3. Pseudoguaianes
2.3.4. Guaianes
2.3.5. Eudesmanes
2.3.6. Caryophyllanes
2.3.7. Bisabolenes
2.3.8. Other Terpene Metabolites
2.4. Diterpenoids
2.5. Flavonoids
2.6. Triterpenoids
2.7. Steroids
2.8. Essential Oils
3. Biological Activities
3.1. Antimicrobial Activities
3.2. Cytotoxic Activities
3.3. Other Activities
4. Conclusions

1. Introduction. – The genus Pulicaria, belonging to the tribe Inuleae of the

Compositae family, consists of ca. 100 species with a distribution from Europe to North
Africa and Asia, particularly around the Mediterranean [1]. Some plants within the
genus are used as traditional herbal medicines. For example, P. crispa, commonly
known as gethgath, is used by the people of Southern Egypt and Saudi Arabia to treat
inflammation and also as an insect repellent and herbal tea [2]. P. odora L. (known

 2010 Verlag Helvetica Chimica Acta AG, Zrich

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locally as Ouden El hallouf), is a Moroccan medicinal plant widely used in traditional

medicine to treat inflammation, back-pain, intestinal disorders, and menstrual cramps,
and this plant is also a constituent of the traditional remedy called Mssakhen, which is
given to women after childbirth. P. dysenterica is reputed for its efficacy for the
treatment of dysentery in the UK [3]; in addition, the decoction from this plant is also
used as an antidiarrhoeal agent in Iran [4]. Phytochemical studies on Pulicaria species
have yielded some flavonoids and terpenoids, including sesquiterpenoids and
diterpenoids. Most importantly, a number of compounds from Pulicaria species have
been found to possess potent bioactivities, and they could be promising candidates for
the development of potential drugs and value-added products. With the purpose of
giving an overview of the important bioactivities, structural complexity, and interesting
chemical diversity of the composition of the genus, herein we review systematically the
articles reported over the past few decades (1968 – 2008), concerning the isolation,
structural elucidation, and biological activities of Pulicaria components.

2. Chemical Constituents. – To the best of our knowledge, the first phytochemical

investigation on Pulicaria species can be traced back to 1968 [5]. Since then, various
types of chemical constituents within the genus Pulicaria have been reported, including
phenolic derivatives, monoterpene derivatives, sesquiterpenes, diterpenes, flavonoids,
triterpenes, steroids, essential oils, and some others. Until 2008, ca. 230 compounds
have been found in 21 Pulicaria species, and their structures are shown below, and their
names and the corresponding plant sources are collected in the Table. As can be seen
from the Table, flavonoids and sesquiterpenoids are the dominant constituents within
the genus Pulicaria.
2.1. Phenolic Derivatives. Eleven phenolic derivatives, 1 – 11, have been isolated
from Pulicaria species, their structures, names, and sources being shown in the Table
and the Formulae.
2.2. Monoterpenes. Ten monoterpenes were identified from the genus Pulicaria.
Among these compounds, 12 – 19 are thymol derivatives, of which the OH groups are
sometimes acylated with an isobutyric acid. Additionally, the isomeric compounds 20
and 21, as the components of essential oils, were both isolated from P. undulata
[19] [21].
2.3. Sesquiterpenoids. Sesquiterpenoid compounds are the main components from
Pulicaria and exhibit a variety of carbon skeletons, such as germacranes, xanthanes,
pseudoguaianes, guaianes, eudesmanes, caryophyllanes, bisabolenes, etc.
2.3.1. Germacranes. In this group, the C(15)-atom is always isolated (Me group),
but C(6), C(8), and C(14) are generally oxygenated. From the aerial parts of P.
canariensis, eleven new sesquiterpene derivatives, pulicanadienes A, B, and C (22, 23,
and 24, resp.), pulicanone (25), pulicanol (26), pulicanarals A, B, and C (27, 28, and 29,
resp.), pulicanadienals A and B (30 and 31, resp.), and pulicanadienol (32), were
reported by Triana and co-workers in 2005, and the structure elucidations of the
compounds were carried out by extensive spectral data interpretation as well as
chemical transformations [22]. In addition, a phytochemical investigation of the hexane
extract of the aerial parts of P. glutinosa Gaertn. furnished two new germacrane
sesquiterpenes, namely puliglene (33) and epoxypuliglene (34). Their NMR signals
indicated that they were conformationally mobile at room temperature. However, 34
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showed one major conformer in the NMR spectra recorded at 958 and 33 remained
broad and ambiguous at temperatures up to 958. Finally, single-crystal X-ray analysis
established the structure and relative configuration of each compound [23].
2.3.2. Xanthanes. The most representative species that produced this sesquiterpe-
noid type is the species P. crispa. Out of 14 xanthanolides, twelve were found in the
species. In 1979, the nine xanthanolides 35 – 38, 42, and 45 – 48 were isolated from P.
crispa from Assuit by El-Emary and co-workers [24]. An extract of the same plant
collected from Elkuraiemat-Elzafarana road (Eastern desert, Egypt) in April 1987,
yielded eight compounds, 35 – 38, 40, and 42 – 44 [25]. From a chemotaxonomic point of
view, it should be pointed out that the secondary metabolites of this species depend on
the genetic bases rather than ecological environments. In addition, in an investigation
of the aerial parts of P. sicula, six xanthanolides, 35 and 37 – 41, were obtained [16]. And
this skeleton type was also found in other species, such as in compounds 39 and 41 from
P. incisa [28], and 36 from P. undulata [26].
2.3.3. Pseudoguaianes. Only four pseudoguaianolides were isolated from Pulicaria
species, and mainly distributing in the species P. crispa. The ether extract of P. crispa
from Egypt afforded three compounds, 8-epiconfertin (49), 10a-hydroxy-8-epiconfer-
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Table. Chemical Constituents from the Genus Pulicaria

No. Compound class and name Source Ref.

Phenolic Derivatives
1 Benzoic acid P. angustifolia [6]
2 p-Hydroxybenzoic acid P. paludosa [7]
3 Veratric acid P. paludosa [8]
4 Anisic acid P. paludosa [8]
5 p-Methoxyacetophenone P. paludosa [8]
6 1-Acetyl-2-hydroxy-4,6-dimethoxybenzene P. incisa [9]
P. undulata [10]
P. arabica [11]
7 Caffeic acid P. dysenterica [5]
8 Eugenol P. paludosa [7]
9 Cinnamic acid P. paludosa [7]
10 1,3,5-Trimethoxybenzene P. laciniata [12]
11 5-Hydroxy-2-methyl-2,3-dihydro-4H-chromen-4-one P. wightiana [13]
Monoterpenes
12 2-Isopropyl-4-methylphenol P. odora [14]
13 2-Isopropyl-4-methylphenyl isobutyrate P. odora [14]
14 Thymol P. arabica [15]
15 Thymol isobutyrate P. arabica [15]
16 10-( Isobutyryloxy)-8,9-didehydrothymol isobutyrate P. sicula [16]
17 10-( Isobutyryloxy)-8,9-epoxythymol isobutyrate P. sicula [16]
P. arabica [15]
P. dysenterica [17] [18]
18 4-Isopropyl-3-methoxybenzyl isobutyrate P. dysenterica [17] [18]
19 4-Hydroxy-2-isopropyl-5-methylphenyl acetate P. undulata [19] [20]
P. undulata [20]
20 2-Methyl-5-(propan-2-yl)cyclohex-2-en-1-one P. undulata [19] [21]
(Carvotanacetone)
21 3-Methyl-6-(propan-2-yl)cyclohex-3-en-1-one P. undulata [20]
Germacranes
22 (1E,4E )-7bH-6a,8b-Diacetoxygermacra-1(10),4-dien- P. canariensis [22]
14-oic acid ( Pulicanadiene A)
23 (1E,4E )-7bH-6a,8b-Diacetoxygermacra-1(10),4-dien- P. canariensis [22]
14-al ( Pulicanadiene B )
24 (1E,4E )-7bH-6a,8b-Diacetoxygermacra-1(10),4-dien- P. canariensis [22]
14-ol ( Pulicanadiene C)
25 (1E)-7bH-6a,8b,14-Trihydroxygermacra-1(10),4(15)- P. canariensis [22]
dien-5-one (Pulicanone)
26 (1E)-7bH-4a,5b-Epoxy-8b-acetoxygermacr-1(10)-en- P. canariensis [22]
6a,14-diol (Pulicanol)
27 (4E)-7bH-1b,10a-Epoxy-6a,8b-diacetoxygermacr-4-en- P. canariensis [22]
14-al ( Pulicanaral A )
28 7bH-1b,10a;4a,5b-Diepoxy-6a,8b-diacetoxygermacran-14-al P. canariensis [22]
( Pulicanaral B )
29 7bH-1b,10a;4a,5b-Diepoxy-8b-acetoxy-6a-hydroxy- P. canariensis [22]
germacran-14-al (Pulicanaral C )
30 (1E,5E,8R )-7bH-4a,8b-Dihydroxygermacra-1(10),5-dien- P. canariensis [22]
14-al ( Pulicanadienal A )
31 (1E,5E )-7bH-8b-Acetoxy-4a-hydroxygermacra-1(10),5-dien- P. canariensis [22]
14-al ( Pulicanadienal B )
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Table (cont.)
No. Compound class and name Source Ref.
32 (1E,5E )-7bH-Germacra-1(10),5-diene-4a,8b,14-triol P. canariensis [22]
( Pulicanadienol)
33 Puliglene P. glutinosa [23]
34 Epoxypuliglene P. glutinosa [23]
Xanthanes
35 8-Epixanthatin P. crispa [24] [25]
P. sicula [16]
36 Xanthatin P. crispa [24] [25]
P. undulata [26]
37 Xanthinosin P. crispa [24] [25] [27]
P. sicula [16]
38 Tomentosin P. crispa [24] [25] [27]
P. sicula [16]
39 7aH,8aH,10aH-2-Hydroxy-4-oxoxanth-11(13)-en-12,8b-olide P. sicula [16]
P. incisa [28]
40 7aH,8bH,10aH-2-Hydroxy-4-oxoxanth-11(13)-en-12,8a-olide P. sicula [16]
P. crispa [25]
41 7aH,8aH,10aH-1b,5b-Epoxy-4-oxoxanth-11(13)-en-12,8b-olide P. sicula [16]
P. incisa [28]
42 7aH,8aH,10aH-2,4-Diacetoxyxanth-11(13)-en-12,8b-olide P. crispa [24] [25]
(Grafin acetate)
43 7aH,8aH,10aH-4-Hydroxy-2-acetoxyxanth-11(13)-en-12,8b-olide P. crispa [25]
44 7aH,8aH,10aH-2-Hydroxy-4-acetoxyxanth-11(13)-en-12,8b-olide P. crispa [25]
45 7aH,8aH,10aH-4-Hydroxyxanth-11(13)-en-12,8a-olide P. crispa [24] [25]
( Desacetyl xanthanol)
46 7aH,8aH,10aH-4-Hydroxy-2-acetoxyxanth-11(13)-en-12,8a-olide P. crispa [24]
47 7aH,8aH,10aH-2-Hydroxy-4-acetoxyxanth-11(13)-en-12,8a-olide P. crispa [24]
48 7aH,8aH,10aH-2,4-Diacetoxyxanth-11(13)-en-12,8a-olide P. crispa [24]
( Xanthanol acetate)
Pseudoguaianes
49 8-Epiconfertin P. crispa [25]
P. undulata [26]
P. laciniata [29]
50 2,3-Dihydro-5,10-epiaromatin P. crispa [2]
51 10a-Hydroxy-8-epiconfertin P. crispa [25]
52 10a,14-Epoxy-8-epiconfertin ( Pulicariolid) P. crispa [24] [25]
P. paludosa [30]
Guaianes
53 1,2-Dehydro-1,10a-dihydropseudoivalin P. crispa [2] [25] [27]
P. sicula [16]
54 5aH-4b,10b-Dihydroxyguaia-1(2),11(13)-dien-12,8a-olide P. crispa [27]
55 Gaillardin P. uliginosa [31]
56 5aH-4a-Hydroxyguaia-1(10),11(13)-dien-12,8a-olide P. crispa [27]
P. sicula [16]
57 7aH,8aH,10aH-2a,4a-Dihydroxyguaia-1(5),11(13)-dien-12,8b-olide P. crispa [2]
58 5aH-1b,4b-Dihydroxyguaia-10(14),11(13)-dien-12,8a-olide P. crispa [27]
59 5aH-1b,4b-Diacetoxyguaia-10(14),11(13)-dien-12,8a-olide P. crispa [27]
60 1aH,5aH-4a-Hydroxyguai-11(13)-en-12,8a-olide P. incisa [28]
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Table (cont.)
No. Compound class and name Source Ref.
61 4a-Hydroxy-5aH-guaia-10(14),11(13)-dien-12,8b-olide P. crispa [25]
P. sicula [16]
P. incisa [28]
62 5aH-4a-Hydroxyguaia-10(14),11(13)-dien-12,8a-olide P. crispa [25]
63 5aH,7aH,8aH,10aH-1a,2a-Epoxy-4b-hydroxyguai-11(13)- P. crispa [2]
en-12,8b-olide
64 5aH,7aH,8aH,10aH-1a,2a-Epoxy-4a-hydroxyguai-11(13)- P. sicula [16]
en-12,8b-olide
65 1aH,10aH-11-Hydroxy-4a,5a-epoxy-13-norguai-7(11)-en- P. undulata [26]
12,8a-olide
66 1aH,10aH-4a,5a-Epoxyguai-11(13)-en-12,8a-olide P. undulata [26]
P. laciniata [29]
67 Liguloxid-3b-ol P. paludosa [32]
68 Liguloxid-3-one P. paludosa [32]
69 Cycloepoxypuliglene P. glutinosa [33]
Eudesmanes
70 2a-Hydroxyalantolactone P. crispa [34]
P. undulata [26]
71 2a-Hydroxyeudesma-4(5),11(13)-dien-12,8b-olide P. undulata [26]
72 Pulicaria glaucolide P. undulata [26]
73 2a-Hydroxy-5a,6a-epoxyalantolactone P. crispa [35]
74 1b,4b-Dihydroxy-6,15a-epoxyeudesmane P. canariensis [22]
75 Oplodiol P. paludosa [32]
76 Isoplodiol P. paludosa [32]
Caryophyllanes
77 Buddledin C P. prostrata [36]
78 Caryophyllene P. paludosa [7] [30]
P. dysenterica [18]
79 Caryophyllene epoxide P. angustifolia [6]
80 (5Z)-12-Hydroxy-14-isobutanoyloxycaryophylla-2(15),5- P. paludosa [32]
dien-7-one
81 (5Z)-12-Hydroxy-14-(2-methylbutanoyloxy)caryophylla- P. paludosa [32]
2(15),5-dien-7-one
82 (1S,5Z,9R )-12,14-Diacetoxycaryophylla-2(15),5-dien-7-one P. dysenterica [17]
P. arabica [15]
83 (1S,5Z,9R,11S )-14-Methoxy-12-acetoxycaryophylla-2(15),5- P. dysenterica [17]
dien-7-one
84 (1S,5E,9R,11S )-14-Methoxy-12-acetoxycaryophylla-2(15),5- P. dysenterica [17]
dien-7-one P. arabica [15]
85 (1S,5Z,9R )-12-Acetoxy-14-hydroxycaryophylla-2(15),5- P. dysenterica [17]
dien-7-one P. arabica [15]
P. paludosa [32]
86 (5Z)-14-Hydroxycaryophyllen-7-one P. arabica [15]
P. scabra [37]
P. paludosa [30]
87 (5Z)-14-Acetoxycaryophyllen-7-one P. arabica [15]
P. dysenterica [17]
P. scabra [37]
P. paludosa [30]
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Table (cont.)
No. Compound class and name Source Ref.

88 (1S,5Z,9R )-12-Hydroxy-14-acetoxycaryophylla-2(15),5-dien-7-one P. dysenterica [17]

P. arabica [15]
89 (1S,5Z,9R )-14-Methoxycaryophylla-2(15),5-dien-7-one P. dysenterica [17]
90 (1S,5Z,9R )-12,14-Dihydroxycaryophylla-2(15),5-dien-7-one P. dysenterica [17]
P. paludosa [32]
91 (1S,9R )-7bH-12-Acetoxycaryophylla-2(15),5E-diene-7,14-diol P. dysenterica [17]
P. arabica [15]
92 (1S,9R )-5aH-5,12-Dihydroxycaryophylla-2(15),6(14)-dien-7-one P. dysenterica [15]
P. arabica [17]
93 5aH-12-Hydroxy-5-methoxycaryophylla-2(15),6(14)-dien-7-one P. arabica [15]
94 5aH-12-Acetoxy-5-methoxycaryophylla-2(15),6(14)-dien-7-one P. dysenterica [17]
P. arabica [15]
95 5bH-12-Acetoxy-5-methoxycaryophylla-2(15),6(14)-dien-7-one P. dysenterica [17]
P. arabica [15]
96 5bH-5,12-dihydroxycaryophylla-2(15),6(14)-dien-7-one P. arabica [15]
P. paludosa [32]
97 5bH-5-Methoxycaryophylla-2(15),6(14)-dien-7-one P. dysenterica [17]
98 5aH-5-Methoxycaryophylla-2(15),6(14)-dien-7-one P. dysenterica [17]
99 (1S,5S,6S,9R,11S )-5,4-Dimethoxy-12-acetoxycaryophyll- P. dysenterica [17]
2(15)-en-7-one
100 (1S,5S,6S,9R,11S )-5,4-Dimethoxy-12-hydroxycaryophyll- P. dysenterica [17]
2(15)-en-7-one
101 (1S,6R,9R )-14-Hydroxycaryophyll-2(15)-en-7-one P. dysenterica [17]
102 (1S,6R,9R,11R )-13,14-Dihydroxycaryophyll-2(15)-en-7-one P. dysenterica [17]
103 (5E)-14-Hydroxycaryophyllen-7-one P. scabra [37]
104 14-Acetoxy-5,6-trans-caryophyllen-7-one P. scabra [37]
105 6,14-Didehydro-5,6-dihydro-5,13-dihydroxycaryophyllen-7-one P. dysenterica [18]
106 14-Acetoxy-13-hydroxycaryophyllen-7-one P. dysenterica [18]
107 13-Acetoxy-14-hydroxycaryophyllen-7-one P. dysenterica [18]
108 13,14-Diacetoxycaryophyllen-7-one P. dysenterica [18]
109 14-Acetoxycaryophyllen-7-one P. dysenterica [18]
110 (5Z)-13,14-Dihydroxycaryophyllen-7-one P. dysenterica [18]
111 (5Z)-14-Acetoxy-13-hydroxycaryophyllen-7-one P. dysenterica [18]
112 (5Z)-13-Acetoxy-14-hydroxycaryophyllen-7-one P. dysenterica [18]
113 Pulidysenterin P. dysenterica [18]
114 Bis-[(5Z )-7-oxocaryophyllene]-14-O-ether P. arabica [15]
115 Puliscabrin P. scabra [37]
116 (5Z)-Puliscabrin P. scabra [37]
117 (5Z)-5’-Epipuliscabrin P. scabra [37]
118 2,15-Dihydropuliscabrin-4,14-dione P. scabra [37]
Bisabolenes
119 Puliglutoic acid P. glutinosa [38]
120 Puliglutal P. glutinosa [33] [38]
121 Puliglutol P. glutinosa [33] [38]
122 Puliglutone P. glutinosa [33]
Other Terpene Metabolites
123 Alloaromadendrane-10b,14-diol P. paludosa [32]
124 Viridiflorol P. paludosa [32]
125 T-Cadinol P. paludosa [32]
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Table (cont.)
No. Compound class and name Source Ref.
126 14-Hydroxy-T-cadinol P. paludosa [32]
127 1a-Hydroxyisocomene P. scabra [37]
128 1b-Hydroxyisocomene P. dysenterica [18]
129 Presilphiperfolanol P. dysenterica [18]
130 Paludolone P. paludosa [30]
131 15-Hydroxyoplop-10(14)-en-4-one ( Pulioplopanone A ) P. canariensis [22]
132 10a,15-Dihydroxyoplopan-4-one ( Pulioplopanone B ) P. canariensis [22]
133 2-(3,4,5,6,7,8,9,10-Octahydro-2,6-dimethyl-5,8-oxaazulen-9-yl)acrylic P. laciniata [12]
acid (Lacitemzine)
134 Secocrispiolid P. crispa [24]
135 2a,6a-Dimethyltetracyclodecal-3-ene-2,12-diol-13,8b-olide P. crispa [39]
( Pulicrispiolide)
136 Pulicaral P. paludosa [8]
137 Pulicaric acid P. paludosa [8]
138 9-Glucopyranosylpropanopentalene-3-carboxaldehyde P. paludosa [8]
139 9-(2’,3’,4’,6’-Tetraacetylglucopyranosyl)oxypropanopentalene-3- P. paludosa [8]
carboxylic acid
140 Corchoionol C P. undulata [40]
141 Roseoside A P. undulata [40]
142 Loliolide P. incisa [28]
Diterpenoids
143 (1E,3Z)-6a,7a-Dimethyl-10-methylidene-6-[2-(3-oxo-2,6-dioxa- P. angustifolia [6]
bicyclo[3.1.0]hex-4-yl)ethyl]cyclodeca-1,3-diene-1-carboxylic acid
144 (1E,3Z)-6a,7a-Dimethyl-10-methylidene-6-[2-(5-oxo-2,5-dihydro- P. angustifolia [6]
furan-3-yl)ethyl]cyclodeca-1,3-diene-1-carboxylic acid
145 15-Deoxypulic acid P. angustifolia [6]
P. glutinosa [38]
146 Pulic acid P. glutinosa [38]
147 Strictic acid P. glutinosa [38]
148 (1E,3Z)-6a,7b-Dimethyl-10-methylidene-6-[2-(5-oxo-2,5-dihydro- P. somalensis [41]
furan-3-yl)ethyl]cyclodeca-1,3-diene-1-carboxylic acid
149 Hautriwaic acid P. salviifolia [42]
150 trans-6a,13-Dihydroxycleroda-3(4),13(14)-dien-18-oic acid P. salviifolia [43]
( Salvicinolin)
151 trans-6a-Hydroxycleroda-3(4),13(14)-dien-15-olid-18-oic acid P. salviifolia [43]
( Salvicinolide)
152 Hardwickiic acid P. salviifolia [44]
153 Salvicin P. salviifolia [45]
154 trans-15-Acetoxy-6a-hydroxycleroda-3,13-dien-18-oic acid P. salviifolia [46]
( Salvicinin)
155 Methyl 5a-hydroxyconyscabroate P. angustifolia [6]
156 Salvinin P. salviifolia [44]
157 6-Hydroxy-7-oxohardwickiic acid lactone P. gnaphalodes [47]
158 Crispioside A P. crispa [25]
P. incisa [28]
159 Crispioside B P. crispa [25]
P. incisa [28]
160 2a-Hydroxyisopimara-8(14),15-dien-7-one P. wightiana [48]
161 Salvin P. salviifolia [44]
162 Salvicinolide methyl ester P. wightiana [13] [49]
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Table (cont.)
No. Compound class and name Source Ref.
163 Methyl (4aR,5R,6S,7S,8R,8aR )-3,4,4a,5,6,7,8,8a-octahydro-7,8- P. wightiana [13] [49]
dihydroxy-5,6,8a-trimethyl-5-[2-(5-oxo-2,5-dihydrofuran-3-
yl)ethyl]naphthalene-1-carboxylate
164 Methyl (4aR,5S,6R,8S,8aR )-3,4,4a,5,6,7,8,8a-octahydro-8-hydroxy- P. wightiana [13]
5-[2-(5-hydroxy-2-oxo-2,5-dihydrofuran-3-yl)ethyl]-5,6,8a-
trimethylnaphthalene-1-carboxylate
165 Methyl (4aR,5S,6R,8S,8aR )-5-[2-(furan-3-yl)ethyl]-3,4,4a,5,6,7,8,8a- P. wightiana [13] [49]
octahydro-8-hydroxy-5,6,8a-trimethylnaphthalene-1-carboxylate
166 Methyl (4aR,5S,6R,8S,8aR )-3,4,4a,5,6,7,8,8a-octahydro-8-hydroxy- P. wightiana [49]
5,6,8a-trimethyl-5-[2-(2-oxo-2,5-dihydrofuran-3-yl)
ethyl]naphthalene-1-carboxylate
167 Methyl (4aR,5S,6R,8S,8aR )-3,4,4a,5,6,7,8,8a-octahydro-8-hydroxy- P. wightiana [49]
5,6,8a-trimethyl-5-[2-(2,5-dihydrofuran-3-yl)ethyl]-naphthalene-
1-carboxylate
168 3,4,9,5,6,7,8,8a-Octahydro-8a-hydroxy-5a,6a,8aa-trimethyl-5b- P. wightiana [13]
[2-(5-oxo-2,5-dihydrofuran-3-yl)ethyl]naphthalene-18,7b-olide
169 Pulicaroside B P. undulata [40]
170 Steviobioside P. incisa [9]
Flavonoids
171 Dihydrokaempferol P. orientalis [50]
P. arabica [11]
P. undulata [19]
172 7-O-Methylaromadendrin P. incisa [9]
P. undulata [19] [20]
173 Taxifolin 7-methyl ether P. incisa [51]
P. undulata [19]
174 Dihydroquercetin P. arabica [11]
P. undulata [19]
175 Dihydroquercetin 3’,7-dimethyl ether P. undulata [19]
P. canariensis [22]
176 7-O-Methyleriodictyol P. undulata [20]
177 Undulatoside P. undulata [52]
178 7,4’-Di-O-methyldihydrokaempferol P. canariensis [22]
179 Quercetin P. orientalis [50]
P. incisa [9]
P. arabica [11]
P. crispa [53]
180 Quercetin 3-monoglucoside P. orientalis [50]
P. incisa [51]
P. arabica [54]
P. crispa [53]
181 Kaempferol P. orientalis [50]
P. incisa [9]
P. arabica [11]
182 Quercetin 3-methyl ether P. orientalis [50]
P. incisa [9] [51]
P. arabica [11]
P. crispa [53]
 CHEMISTRY & BIODIVERSITY – Vol. 7 (2010) 341

Table (cont.)
No. Compound class and name Source Ref.
183 Kaempferol 3-methyl ether P. orientalis [50]
P. incisa [9] [51]
P. arabica [11]
P. undulata [19]
184 Kaempferol 3,7-dimethyl ether P. orientalis [50]
P. arabica [11]
185 Quercetin 3,3’-dimethyl ether P. incisa [9]
186 Quercetin 3,7-dimethyl ether P. incisa [51]
P. arabica [11]
P. undulata [19]
187 Kaempferol 3-glucoside ( Trifoliin) P. incisa [51]
P. dysenterica [5]
188 6-Methoxykaempferol 3-methyl ether P. paludosa [32]
189 3’-Methylquercetin P. arabica [55]
190 4’-Hydroxy-3,5,6,7,3’-pentamethoxyflavone P. arabica [55]
191 3,5,6,7,3’,4’-Hexamethoxyflavone P. arabica [55]
192 Quercetagetin 3,7-dimethyl ether P. arabica [54]
P. dysenterica [56]
193 Quercetagetin 3,5,7-trimethyl ether P. arabica [54]
194 Quercetagetin 3,5,7,3’-tetramethyl ether P. arabica [54]
195 Quercetagetin 3,6-dimethyl ether ( Axillarin) P. undulata [52]
P. crispa [35]
196 6-Methoxykaempferol P. undulata [52]
197 6-Methoxykaempferol 3-glucoside P. undulata [52]
198 6-Hydroxykaempferol 3-methyl ether 6-glucoside P. dysenterica [56]
199 Quercimetrin P. crispa [53]
200 Quercetagetin 3,6,7,3’-tetramethyl ether P. somalensis [41]
201 Ladanetin P. uliginosa [31]
202 Quercetagetin 3,6,7-trimethyl ether P. somalensis [41]
203 3’,5,6-Trihydroxy-3,4’,7-trimethoxyflavone P. wightiana [13]
204 Scutellarein P. dysenterica [56]
205 6-Hydroxykaempferol 3,7-dimethyl ether P. dysenterica [56]
206 6-Hydroxykaempferol 3,6,7-trimethyl ether P. dysenterica [56]
207 5,6-Dihydroxy-4’,7-dimethoxyflavone P. paludosa [32]
208 5,6,8-Trihydroxy-4’,7-dimethoxyflavone P. paludosa [32]
209 Artemisetin P. arabica [55]
210 Quercetagetin 3,7,4’-trimethyl ether P. dysenterica [5]
211 Quercetagetin 3,6,7,4’-tetramethyl ether P. somalensis [41]
212 5,7-Dihydroxy-3,3’,4’-trimethoxyflavone P. canariensis [22]
213 3’,6-Dihydroxy-3,4’,5,7-tetramethoxyflavone P. salviifolia [57]
214 Quercetin 3-glucuronide P. arabica [54]
215 Quercetin 3-rhamnoglucoside P. salviifolia [45]
216 Pulicaroside P. undulata [52]
Triterpenoids
217 a-Amyrin P. incisa [9]
218 Pseudotaraxasteryl acetate P. paludosa [30]
219 Taraxasteryl acetate P. angustifolia [6]
P. paludosa [30]
P. undulata [19]
P. salviifolia [58]
342 CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)

Table (cont.)
No. Compound class and name Source Ref.
220 b-Amyrin P. crispa [59]
221 Lupeol acetate P. incisa [9]
222 Lupeol P. angustifolia [6]
P. undulata [19]
223 Calenduladio P. canariensis [22]
Steroids
224 b-Sitosterol P. angustifolia [6]
P. arabica [15]
P. crispa [59]
P. salviifolia [58]
225 Sitosterol-3-O-b-glucoside P. incisa [28]
226 Stigmasterol P. angustifolia [6]
P. paludosa [30]
227 Ergosterol peroxide P. canariensis [22]
228 Dammaradienyl acetate P. arabica [15]
229 Cholesterol P. salviifolia [58]

tin (51), and pulicariolid (52) [25]. A further investigation on the same source from
KSIR field station in the Kebd area of Kuwait resulted in the isolation of one
pseudoguaianolide, 50, and its structure was found to be 5,10-epi-2,3-dihydroaromatin
on the basis of extensive 1D- and 2D-NMR experiments [2]. Other Pulicaria species
also produced compounds of this skeleton type, for example, both P. undulata [26] and
P. laciniata [29] yielded compound 49, while P. paludosa afforded compound 52
[30].
2.3.4. Guaianes. As a representative species within the genus, P. crispa from
different locations has been investigated, leading to the isolation of nine guaiane
sesquiterpenes by different groups, i.e., compounds 53, 54, 56, 58, and 59 by Dendougui
et al. [27], compounds 53, 57, and 63 by Stavri et al. [2], as well as compounds 53, 61, and
62 by Abdel-Mogib et al. [25]. Their structures were identified mainly based on NMR
methods. An extract of the aerial parts of P. sicula from Qatar in spring 1987 yielded the
four guaiane compounds 53, 56, 61, and 64, three of which have also been found in P.
crispa. The structures were elucidated by high-field 1H-NMR-spectroscopic methods
[16]. In view of potential chemotaxonomic significance, it is noteworthy that the
isolation of the xanthanolides and the guaianolides may be an indication that P. sicula is
related to P. crispa, which afforded very similar constituents. In addition, in this group,
gaillardin (55) [31], 4a-hydroxy-1aH,5aH-guai-11(13)-en-12,8a-olide (60) [28], 4a,5a-
epoxy-1aH,10aH-guai-11(13)-en-12,8a-olide (66) [29], and cycloepoxypuliglene (69)
[33] have been found in P. uliginosa, P. incisa, P. laciniata, and P. glutinosa, respectively.
In 1991, an extract of the aerial parts of P. undulata furnished the novel norguaianolide
65, representing the so far only example of a Pulicaria sesquiterpenoid with 14 C-atoms,
and the guaianolide compound 66 [26]. Two 4-epiguaianes, liguloxid-3b-ol (67) and
liguloxid-3-one (68) were isolated from P. paludosa [32], and their structures were
established mainly by NMR techniques. A total of 17 guaianes with an O-function in
 CHEMISTRY & BIODIVERSITY – Vol. 7 (2010) 343

position 4 (except for 67 and 68) have been isolated from the genus, nine of them having
been isolated from P. crispa. From the biosynthetic point of view, both xanthanes and
pseudoguaianes can be proposed to be derived from guaiane as a precursor.
2.3.5. Eudesmanes. The phytochemical investigation of Pulicaria species yielded
only seven eudesmane sesquiterpenes, 70 – 76. Four of them, 2a-hydroxyalantolactone
(70) from P. crispa [34] and P. undulata [26], 2a-hydroxyeudesma-4(5),11(13)-dien-
12,8b-olide (71) from P. undulata [26], pulicaria glaucolide (72) from P. undulata [26],
and 2-hydroxy-5a,6a-epoxyalantolactone (73) from P. crispa [35] share similar
structures with a OH function at C(2) and a g-lactone ring closed toward C(8). In
addition, from P. canariensis, one known eudesmane, 74, has been found, and the
structure was elucidated as 6,15a-epoxy-1b,4b-dihydroxyeudesmane by comparison of
its spectroscopic properties with the published data [22]. At the same time, the isomeric
compounds oplodiol (75) and isoplodiol (76) were isolated from P. paludosa, and their
structures were established by 1H-NMR data and chemical transformations [32].
2.3.6. Caryophyllanes. This is the largest group of known Pulicaria sesquiterpenoids.
Out of the total 121 sesquiterpenoids, 42 belong to this group, including six dimeric
sesquiterpenes. In this group, all compounds share very similar structures (4/9-bicyclic
C-skeleton) with the C¼C bond at C(2). Often C(5), C(7), C(12), and C(14) are
functionalized by an O-function. The group appears to be widely distributed within the
genus. The structure of one sesquiterpene ketone, buddledin C (77), which was easily
isolated by steam distillation during the preparation of an essential oil from the aerial
parts of the species P. prostrata, was confirmed by performing an X-ray structure
analysis [36]. In this genus, two species often yield caryophyllene compounds. One
species is P. dysenterica. In 1992, Marco and co-workers investigated specimens of P.
dysenterica growing in Spain and isolated six new compounds, 83, 89, and 99 – 102,
together with twelve known ones, 82, 84, 85, 87, 88, 90 – 92, 94, 95, 97, and 98. The
structures were determined by means of MS and NMR experiments [17]. The other
species is P. arabica. The structures of the twelve compounds, 82, 84 – 88, and 91 – 96,
isolated from the aerial parts of P. arabica were elucidated by MS and high-field
1
H-NMR spectroscopy [15]. An early investigation of the aerial parts of P. dysenterica,
grown from seeds supplied by the Botanic Garden Liège, afforded seven caryophyllene
derivatives with oxygen functions at the C(13)-atom, compounds 105 – 108 and 110 –
112, as well as two with an isolated Me group at C(13), compounds 78 and 109. The
structures of these compounds were established on the basis of spectroscopic
techniques and chemical transformations [18]. Many other caryophyllenes were also
identified from different Pulicaria species, such as caryophyllene (78) from P. paludosa
[7] [30], caryophyllene epoxide (79) from P. angustifolia [6], 80, 81, and 85 from P.
paludosa [32], 86 and 87 from P. scabra [37] and P. paludosa [30], 90 and 96 from P.
paludosa [32], and 103 and 104 from P. scabra [37]. Additionally, the genus also yielded
dimeric sesquiterpenes. From the aerial parts of P. scabra, four more complicated
compounds, the ether-linked caryophyllanes 115 – 117 and the ester 118 were isolated.
The structures and configurations were elucidated on the basis of extensive spectral
analysis [37]. Compound 113, named pulidysenterin, which was an additional example
of a sesquiterpene alcohol esterified with a sesquiterpenic acid, was isolated from P.
dysenterica [18]. Compound 114, the dimeric ether formed from compound 86, was
found in P. arabica [15].
344 CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)

2.3.7. Bisabolenes. In 1992, El-Feraly and co-workers published two articles on P.

glutinosa, reporting four bisabolene sesquiterpenes, namely puliglutoic acid (119),
puliglutal (120), puliglutol (121), and puliglutone (122), and the structures were
determined mainly by spectroscopic methods [33] [38]. Up to now, only the species P.
glutinosa was found to afford bisabolene sesquiterpenes within the genus Pulicaria.
2.3.8. Other Terpene Metabolites. Except for the above skeletons, other sesquiter-
pene types including aromadendrane, cadinane, isocomene, presilphiperfolane, oplo-
panane, and modhephane, and so on, were also identified from the genus. From the
neutral part of P. paludosa, four sesquiterpenes were identified respectively as allo-
aromadendrane-10b,14-diol (123), viridiflorol (124), T-cadinol (125), as well as 14-
hydroxy-T-cadinol (126) by direct comparison with the literature data [32]. An extract
of the same source by the other study group yielded paludolone (130) [30]. Two
isocomenes, 1a-hydroxyisocomene (127) and 1b-hydroxyisocomene (128), were found
in the species P. scabra [37] and P. dysenterica [18], respectively. A phytochemical
investigation on P. dysenterica afforded presilphiperfolanol (129), as the precursor of
polycyclopentanoid hydrocarbons [18]. Further investigation of the species P.
canariensis led to the isolation of two new compounds, pulioplopanones A and B
(131 and 132, resp.) [22]. Lacitemzine (133) was reported as a novel sesquiterpene from
P. laciniata, and its structure was elucidated as 2-(3,4,5,6,7,8,9,10-octahydro-2,6-
dimethyl-5,8-oxaazulen-9-yl)acrylic acid by spectroscopic procedures including 2D-
NMR and X-ray-diffraction methods [12]. The structures of four modhephanes, namely
pulicaral (136), pulicaria acid (137), and two glycosides 138 and 139, isolated from P.
paludosa, were determined by interpretation of their spectral data, mainly by 1D-, 2D-
NMR, and NOE differences results [8]. In addition, other Pulicaria species also yielded
five sesquiterpenoids, namely secocrispiolid (134) from P. crispa [24], pulicrispiolide
(135) from P. crispa [39], corchoionol C (140) and roseoside A (141) from P. undulata
[40], as well as loliolide (142) from P. incisa [28].
2.4. Diterpenoids. An extract of the whole air-dried plant of P. angustifolia from
Rajasthan and India afforded four diterpenes derived from clerodane, the seco-
nidoresedic acid derivatives 143 – 145 and methyl 5a-hydroxyconyscabroate (155), and
their structures were elucidated by spectroscopic methods [6]. The aerial parts of P.
glutinosa yielded three clerodanes, strictic acid (147), and two new derivatives, pulic
acid (146) and 15-deoxypulic acid (145, originally isolated from P. angustifolia). Their
structural assignments were mainly based on 1D- and 2D-NMR spectroscopic data
[38]. One compound, cyclodeca-1,3-diene-1-carboxylic acid 148 was isolated from P.
somalensis [41]. P. salviifolia was systematically investigated by Nurmukhamedova and
co-workers, four diterpenoids, hardwickiic acid (152) [44], salvicin (153) [45], salvinin
(156) [44], and salvin (161) [44] were isolated. Further investigation on the same
species by Éshbakova et al. during the period 1994 – 2003 yielded four diterpenoids,
hautriwaic acid (149) [42], salvicinolin (150) [43], salvicinolide (151) [43], and
salvicinin (154) [46]. Spectral data and chemical transformations provided their
structures. In 1992, a new isopimarane, which was characterized as 2a-hydroxyisopi-
mara-8(14),15-dien-7-one (160) based on spectral data, was isolated from P. wightiana
[48]. In 2005 and 2006, Das et al. published two articles on P. wightiana, and seven
clerodane diterpenoids 162 – 168 were reported. The structures and configurations of
these compounds were established from spectral data, including 1D- and 2D-NMR
 CHEMISTRY & BIODIVERSITY – Vol. 7 (2010) 345

[13] [49]. In this group, five other compounds, 6a-hydroxy-7-oxohardwickiic acid

lactone (157) [47], crispiosides A and B (158 and 159, resp.) [25], pulicaroside B (169)
[40], as well as steviobioside (170) [9], have been found in four different species, P.
gnaphalodes, P. crispa, P. undulata, and P. incisa, respectively.
2.5. Flavonoids. A total of 46 flavonoids, 171 – 216, have been identified since the
first study on the genus Pulicaria, and they represent a large group of the known
Pulicaria compounds. This class within the genus can be divided into four subgroups:
flavone derivatives, flavonol derivatives, flavanone, and flavanonol derivatives, all of
them bearing O-functions at positions 5, 7, and 4’. However, C(2’), C(6’), and C(8)
(except for 208) have never been functionalized. Among these compounds, nine
compounds, undulatoside (177) [52], quercetin 3-monoglucoside (180) [50], trifoliin
(187) [5] [51], 6-methoxykaempferol 3-glucoside (197) [52], 6-hydroxykaempferol 3-
methyl ether 6-glucoside (198) [56], quercimetrin (199) [53], quercetin 3-glucuronide
(214) [54], quercetin 3-rhamnoglucoside (215) [45], and pulicaroside (216) [52], as
glycosides were isolated from different species.
2.6. Triterpenoids. Seven triterpene compounds, 217 – 223, were found in the genus
Pulicaria, and their names, sources, and structures are shown in the Table.
2.7. Steroids. Six steroid compounds, namely b-sitosterol (224) [6] [15] [58] [59],
sitosterol 3-O-b-glucoside (225) [28], stigmasterol (226) [6] [30], ergosterol peroxide
(227) [22], dammaradienyl acetate (228) [15], and cholesterol (229) [58], isolated from
different Pulicaria species.
2.8. Essential Oils. As important constituents in Pulicaria species, essential oils were
also isolated from several species [60 – 62].

3. Biological Activities. – 3.1. Antimicrobial Activities. Aqueous, MeOH, and CHCl3

extracts of P. dysenterica aerial parts were tested for their antibacterial activities against
six pathogens (Shigella dysenteriae, Salmonella typhi, Escherichia coli, Vibrio cholera,
Staphylococcus aureus, and Bacillus cereus) using the disc-diffusion assay technique.
The MeOH extract was found to be the most effective extract against three of the tested
bacteria (S. aureus, B. cereus, and V. cholera), and all of the extracts were active against
V. cholera [62]. The essential oil of P. odora L. was tested against seven bacteria
(Bacillus cereus (IPL 58605), Streptococcus C (IPT 2-035), Proteus vulgaris (CIP
58605), Enterococcus faecalis (CIP 103214), Escherichia coli (CIP 54127), Pseudomo-
nas aeroginosa (CIPA 22), and Enterococcus faecalis) at different concentrations. The
results showed that the essential oil exhibited a significant antibacterial activity; at low
quantities (5 mg/disc), the essential oil of P. odora L. showed inhibition zones against all
bacteria. A strong antibacterial activity was observed against Streptococcus C, B. cereus,
E. faecalis, and P. vulgaris [61]. In addition, the antibacterial activity was exhibited by
the MeOH extract of P. stephanocarpa [63]. The EtOH extract from P. orientalis
showed very weak antibacterial activity (IC50 18 mg/ml) [64]. The antibacterial
activities of the constituents 162 – 168 were evaluated by the agar cup bioassay method.
The compounds showed moderate activity against Gram-positive organisms, Bacillus
subtilis (MTCC-441), Bacillus sphaericus (MTCC-511), and Staphylococcus aureus
(MTCC-96). However, they were less active against Klebsiella aerogenes (MTCC-39)
and Chromobacterium violaceum (MTCC-2656), and inactive against Pseudomonas
aeruginosa [13] [49]. Six strains of bacteria were tested: Staphylococcus aureus (ATCC
346 CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)

25923), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853),

Salmonella typhimurium (ATCC 43971), Vibrio colerae (ATCC 14033), and Strepto-
coccus pyogenes (HITM 100), as well as one fungal strain Candida albicans (HITM 22)
by the diffusion method. The results showed that the essential oil of P. odora and
compound 12 possess an inhibitory activity against all bacteria and yeast tested with
MIC ranging from 1 to 2 ml/ml, except for P. aeruginosa (ATCC 27853), by contrast,
compound 13 was inactive against all organisms tested [14]. Compound 50 exhibited
weak antimycobacterial activity against Mycobacterium phlei with a MIC value of
0.52 mm [2]. Compounds 145 – 147 and 119 – 121 were tested for antimicrobial activities,
and only strictic acid showed moderate activity against Gram-positive bacteria and the
yeast C. albicans [38]. After an antimicrobial screen of compound 70 against five
microorganisms, Staphylococcus aureus (NCTC 657l), Escherichia coli (NCTC 10418),
Pseudomonas aeruginosa (NCTC 10662), Salmonella sp., and Candida albicuns
(NCTC 3153), the results showed a slight activity against S. aureus only (MIC
0.625 mg/ml) [34].
3.2. Cytotoxic Activities. Compounds isolated from P. canariensis were tested for
their cytotoxic activities against the human myeloid leukemia cell line HL-60 by the
MTT assay. It was found that acetylation of pulicanone (25) and pulicanol (26),
pulicanarals A and B (27 and 28, resp.), and pulioplopanone A (131) showed weak
cytotoxic activities with IC50 values (in mm) of 20  7, 298  22, 115  18, 264  6, and
242  80, respectively. The triacetate of pulicanone was the most potent compound, and
the cytotoxicity was caused by induction of apoptosis as determined by microscopy of
nuclear changes, activation of caspases, and the cleavage of poly (ADP-ribose)
polymerase-1 [22]. In 2008, during biological activity studies on the species P. crispa,
compound 50 was evaluated in vitro for anticancer activity in an established human
bladder carcinoma cell line, EJ-138. It demonstrated promising activity in this cell line,
with an IC50 value of 5.8  0.2 mm [2]. Compound 70 was cytotoxic (0.2 mg/ml in 9 KB;
2 mg/ml in 9 PS) and showed borderline activity against the murine P-388 lymphocytic
leukemia (T/C 123% at 75 mg/kg) [34]. Compound 73 was shown to be cytotoxic to KB
cells in culture (ED50 ¼ 0.4 mg/ml), and the parent compound 70 was found to be active
at almost the same level (ED50 ¼ 0.33 mg/ml) [35].
3.3. Other Activities. Axillarin (195) possesses anticarcinogenic activity using the
assay for benzo[a]pyrene metabolism in cultured hamster embryo cells, results showed
that axillarin is active at 25 mg/ml medium and decreased the metabolism of
benzo[a]pyrene by an average of 61.3% over DMSO controls [35]. In 1997, Ross et al.
reported that carvotanacetone 20 did not show antimicrobial activity against Candida
albicans B311 and Cryptococcus neoformans (50 ml, 1 mg/ml), as compared to
amphotericin B. No cytotoxicity against K562 cells, human chronic myelogenous
leukemia and KB cells, human oral epidermoid carcinoma, or antiviral activity was
found [60]. In addition, antispasmodic activities of P. glutinosa have been demonstrated
[65], and P. dysenterica showed an antihistaminic effect [66].

4. Conclusions. – From the results obtained, it was concluded that chemical

constituents from Pulicaria species exhibit a variety of carbon skeletons and many
compounds showed significant bioactivities. About 21 Pulicaria species, part of the
genus, have been studied from 1968 to 2008, and 230 compounds have been isolated and
 CHEMISTRY & BIODIVERSITY – Vol. 7 (2010) 347

characterized (66 references). However, even among these species, only a few were
intensively investigated. To search for more potential bioactive components, further
phytochemical and biological-activity studies on more species of the genus are
required.

This work was supported by National Natural Science Foundation of China (NSFC 20621091), the
National 863 Program of China (No. 2007AA09Z403), and National Key Technology Research and
Development Program of China (No. 2007BAI37B05).

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Received January 15, 2009