Review
Blackwell Science, Ltd
Research review
Emodin – a secondary metabolite with
multiple ecological functions in higher
plants
Author for correspondence:
Ido Izhaki
Tel: +1 352 392 9169
Fax: +1 352 392 3704
Email: [email protected]
Ido Izhaki
Department of Biology, Faculty of Science and Science Education, University of Haifa at Oranim, Tivon
36006, Israel; Present address: Department of Zoology, University of Florida, Gainesville, FL 32611–
8525, USA
Received: 10 April 2002
Accepted: 3 May 2002
Summary
Key words: secondary metabolites,
multifunctionality, emodin, herbivory
and frugivory, plant fitness,
allelopathy, seed dispersal,
antimicrobial activity.
The anthraquinone emodin, identified in 17 plant families distributed worldwide, has
numerous biological activities, some of which exhibit a wide spectrum of ecological
impacts by mediating biotic or abiotic interactions of plants with their environment.
Here the evidence for direct and indirect effects of emodin on plant survival and
reproduction is reviewed. Emodin in vegetative organs may help protect plants
against herbivores, pathogens, competitors and extrinsic abiotic factors (e.g. high
light intensities). In unripe fruit pulp, emodin may facilitate seed dispersal by protecting the immature fruit against predispersal seed predation whereas in ripe pulp
it may deter frugivores and thus reduce the chances that seeds will be defecated
beneath the parent plant. It also accelerates the passage of seeds through the digestive tract, potentially reducing dispersal distance and increasing seed viability upon
dispersal. In certain circumstances both of the last two effects could also have
negative fitness consequences for plants. Natural selection should favor secondary
metabolites with multiple functions because they protect the plants against a variety
of unpredictable biotic and abiotic environments. Such metabolites also enhance
plant defenses by using different molecular targets of specific enemies through a
variety of mechanisms of action. Emodin illustrates the wide and often overlooked
potential for chemical multifunctionality in plant secondary metabolites.
© New Phytologist (2002) 155: 205–217
Introduction
The original definition of chemical compounds as ‘secondary’
emerged from the notion that they are not absolutely essential
to the survival and reproduction of plants (Bentley, 1999).
However, the current concept is that the wide variety of
secondary metabolites that is produced by higher plants
plays important roles in many complex biotic and abiotic
interactions ( Waterman, 1992; Waterman & Mole, 1994). In
several instances a group of related secondary compounds
© New Phytologist (2002) 155: 205–217 www.newphytologist.com
has exhibited more than one biological activity, sometimes
in contradictory modes (Rhoades, 1977; Swain, 1986; Wink,
1999; Cipollini, 2000). The same anthocyanins can act as
attractants to the flower, antioxidants, phytoalexins and as
antibacterial agents (Cooper-Driver & Bhattacharya, 1998).
Many of the same trichome constituents, which are toxic to
insects, are antimicrobial and also have deleterious effects on
mammalian herbivores (Harborne, 1993). The leaf resin of
Larrea spp. deters herbivores, protects against desiccation
and screens UV radiation (Rhoades, 1977). Ripe fruits of
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Solanum often contain glycoalkaloids that possess multiple
biological activities, such as germination inhibition, laxative
effects on mammals, constipating effects on birds, deterrents
to herbivores and more (Cipollini, 2000). Capsaicin in chili
(Capsicum spp.) fruits exhibits multiple functions that
promote seed dispersal (Tewksbury & Nabhan, 2001). Many
alkaloids simultaneously exhibit allelopathic, antibacterial
and animal toxicity effects ( Wink & Schimmer, 1999). Thus,
the same secondary metabolites may act to deter different groups
of organisms by different modes of action. Rhoades (1977)
argued that any chemical substances must be integrated into
the total metabolic scheme of the plant and by nature are
expected to be multifunctional. Wink (1999) claims that
multiple functions of secondary metabolites are common and
do not contradict their main role for chemical defense and
signaling. Furthermore, he argues that natural selection will
favor those metabolites that possess multiple functions.
Here, I illustrate the broad diversity of biological activities
exhibited by one secondary metabolite – emodin. Although
this compound was first described > 75 yr ago (reported as
‘frangula-emodin’, Kögl & Postowsky, 1925), many of its
diverse biological properties have been discovered in the last
decade. I focus on the variety of ecological interactions mediated by emodin and on its role in facilitating plant survival
under the risks induced by biotic and abiotic hazards and also
on the potential cost of its production to plant fitness. I then
discuss several of the ecological and evolutionary aspects of
secondary metabolite multifunctionality.
Emodin: chemical structure and distribution
Emodin belongs to the anthraquinones, a group of > 170
natural compounds that make up the largest group of natural
quinones (Thomson, 1987; Thomson, 1997; Harborne et al.,
1999). More than half of the natural anthraquinones are found
in lower fungi, particularly in Penicillium and Aspergillus
species, and in lichens. Others are found in higher plants,
and, in isolated instances, in insects (Thomson, 1987, 1997;
Evans, 1996). The Rubiaceae, Rhamnaceae, Fabaceae, Polygonaceae, Bignoniaceae, Verbenaceae, Scrophulariaceae and
Liliaceae are particularly rich in anthraquinones (Van den
Berg & Labadie, 1989).
Anthraquinone may either be formed via the acetatemalonate pathway in Polygonaceae and Rhamnaceae or
O-succinylbenzoic acid in the Bignoniaceae and Verbenaceae
(Evans, 1996; Dewick, 1998; Harborne et al., 1999). The basic
chemical structure of anthraquinone is an anthracene ring
(tricyclic aromatic) with two ketone groups in position
C9 and C10 (Fig. 1). In plants, anthraquinones are mostly
present as sugar derivatives – the glycosides – but the free form
– the aglycones – are widely distributed as well (Thomson,
1987, 1997; Harborne et al., 1999). Among the most common naturally occurring anthraquinone aglycones in higher
plants are emodin, rhein, chrysophanol, aloe-emodin, and
Fig. 1 Structural formula of emodin and some other anthraquinone
aglycones and glycosides present in high plants.
physcion (Fig. 1) (Evans, 1996; Harborne et al., 1999). Several
biochemical pathways that transform one anthraquinone
to another have been discovered. For example, chrysophanol
is synthesized in plants by dehydroxylation of emodin, an
enzymatic conversion that is mediated by nicotinamide adenine
dinucleotide phosphate (NADPH) as cofactor (Anderson
et al., 1988). It was also suggested that physion is derived from
emodin (Thomson, 1997). The anthraquinone glycosides
formed when one or more sugar molecules, mostly glucose or
rhamnose, are bound to the aglycone by a β-glycoside linkage to
hydroxyl group at position C8 (in the case of glucose) or the one
at C6 (in the case of rhamnose) (Fig. 1) (Dewick, 1998). Among
the most common emodin-related glycosides are emodin-8glucose, frangulin and glucofrangulin (Harborn et al., 1999)
(Fig. 1).
Emodin (1,3,8-trihydroxy-6-methylanthraquinone, Fig. 1)
is mainly reported in three plant families: Fabaceae (Cassia
spp.), Polygonaceae (Rheum, Rumex and Polygonum spp.) and
Rhamnaceae (Rhamnus and Ventilago spp.) (Table 1). It seems
that this is not a function of the larger number of species
assayed in these families relative to other families but that
emodin is actually more common among species of these
three families. However, a comprehensive literature survey
revealed that emodin has already been identified in at least
17 plant families, 28 genera and 94 species (Table 1). Interesting
records of emodin have been documented recently in Asteraceae, Poaceae and Simaroubaceae, among others (Table 1).
The presence of emodin in Aloe (Liliaceae) is rather controversial (Dange, 1996), and it might be rare in this family.
Emodin has a worldwide distribution, occurring in subtropical
and tropical families (e.g. Bignoniaceae and Simaroubaceae),
in families that mainly inhabit the temperate region (e.g.
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Table 1 Families, genera, number of species (in parentheses) and parts of plants containing emodin
Family
Genus (no. of species)
Plant parts
References
Actinidiaceae
Amaranthaceae
Asteraceae
Actinidia (1)
Achyranthes (1)
Artemisia (1)
Lactuca (1)
Petasites (1)
root
root
whole plant
whole plant
rhizome
Thomson (1997)*
Thomson (1997)*
Mueller et al. (1999)
Mueller et al. (1999)
Thomson (1997)*
Bignoniaceae
Catalpa (1)
stem
Thomson (1997)*
Clusiaceae
Hypericum (3)
Ploiarium (1)
Psorospermum (1)
whole plant
branch
root, bark
Berghofer & Holzl (1987); Makovetska (2000)
Thomson (1997)*
Thomson (1987)*
Cupressaceae
Juniperus (1)
heartwood
Thomson (1997)*
Fabaceae
Cassia (11)
root, bark, stem, leave,
heartwood, seed, pod
Phaseolus (1)
Pisum (1)
whole plant
whole plant
Perry (1980)*; Lewis & Shibamoto (1989);
Singh et al. (1992); Kinjo et al. (1994);
Liang et al. (1995); Abegaz et al. (1996)*
Mueller et al. (1999)
Mueller et al. (1999)
Liliaceae
Aloe (4)
whole plant
Perry (1980)*; Murray (1995)
Myrsinaceae
Myrsine (1)
root
Thomson (1997)*
Plantaginaceae
Plantago (1)
whole plant
Mueller et al. (1999)
Poaceae
Agropyron (1)
root
Mueller et al. (1999)
Polygonaceae
Polygonum (4)
rhizome, root, stem
Rheum (8)
rhizome, leave
Rumex (15)
root, seed, leave,
stem, flower
Perry (1980)*; Huang et al. (1991); Inoue et al. (1992);
Jayasuriya et al. (1992); Schmitt et al. (1998)
Perry (1980)*; Rawat et al. (1988); Tang & Eisenbrand (1992)*;
Liang et al. (1995); Min et al. (1998); Ma et al. (1989);
Paneitz & Westendorf (1999)
Watt & Breyer-Brandwijk (1962)*; Perry (1980)*;
Midiwo & Rukunga (1985); van den Berg & Labadie (1989)*;
Abd el-Fattah et al. (1994); Ghazanfar (1994)*; Hasan et al. (1995);
Choe et al. (1998); Kim et al. (1998); Demirezer et al. (2001)
Rhamnus (23)
bark, leave, stem,
flower, seed, fruit pulp
Ventilago (4)
root, stem, bark
Abou-Chaar & Shamlian (1980); Coskun (1986), (1992);
Dwivedi et al. (1988); van den Berg et al. (1988); Jacobson (1990);
Singh et al. (1992); Ram et al. (1994); Abegaz & Peter (1995);
Paneitz & Westendorf (1999); Sharp et al. (2001)
Thomson (1987*, 1997)*; Pepalla et al. (1992)
Rosaceae
Fragaria (1)
Prunus (1)
stem, leaves
stem, bark
Perry (1980)*
Thomson (1997)*
Saxifragaceae
Bergenia (1)
root, rhizome
Yuldashev et al. (1993)
Simaroubaceae
Bruceae (1)
Picramnia (3)
rhizome
rhizome, stem, bark
Thomson (1997)*
Thomson (1997)*; Rodríguez-Gamboa et al. (2000)
Vitaceae
Vitis (1)
leave
Mueller et al. (1999)
Rhamnaceae
*See References within.
Polygonaceae and Saxifragaceae), and in families inhabiting
both the tropics and the temperate regions (e.g. Rhamnaceae
and Clusiaceae). Furthermore, emodin occurs in diverse life
forms including trees, shrubs, lianas and herbs.
Distribution of emodin among plant organs
Emodin was originally reported as being more common in
bark and roots (Evans, 1996; Bruneton, 1999), but it is clear
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now that emodin is present in other vegetative organs (stem,
foliage) as well as in reproductive organs (flower, fruit, seeds,
pods, Table 1). According to the nonadaptive hypothesis, the
distribution of secondary metabolites within organs may
be roughly equivalent to the distribution of the primary
metabolic pathways responsible for the creation of the
secondary metabolite (as a byproduct) and thus they do not
necessarily have an adaptive function in each organ (Eriksson
& Ehrlén, 1998). However, concentrations of emodin in
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different plant organs are frequently unequal, a phenomenon
found in many secondary metabolites (Zangerl & Bazzaz,
1992; Bernays & Chapman, 1994). For example, the flowers
and roots of Rumex luminiastrum contain higher emodin
concentrations than the leaves (Abd El-Fattah et al., 1994).
The average (± sd) emodin aglycone concentration in
R. alaternus leaves (0.04% ± 0.05% d. wt, n = 14) is 8 times
higher than in unripe fruit (seeds and pulp) (Tsahar, 2001).
From the ecological point of view it is expected that the use
of secondary metabolites in ripe pulp and seeds would
be radically different, as the pulp should reward the seed
disperser with nutrition whereas the seed should remain
unattractive to predators (Waterman, 1992). Indeed, emodin
content in ripe pulp of R. alaternus (0.0017% ± 0.0006%
d. wt, n = 12) is 14 times lower that in the seeds (Tsahar,
2001). The allocation of emodin in various plant organs and
the unequal distribution of emodin concentration among
them may in itself provide circumstantial evidence for multifunctionality of emodin in plants.
Nevertheless, a similar content of secondary metabolites
among organs does not necessarily support the nonadaptive
hypothesis. For example, the similar content of secondary
metabolites (alkaloids, saponins, cyanogenic glycosides,
terpenoids, and phenolics) found in unripe fruits and in
leaves of several species ( Joslyn & Goldstein, 1964; McKey,
1979) may indicate that in these cases a similar secondary
metabolite content is required to fight against the specific
potential enemies of each organ.
Abiotic factors that govern emodin levels in
plants
Synthesis and accumulation of secondary metabolites in plants
is regulated in space and time (Wink & Schimmer, 1999)
and is affected by abiotic environmental factors, such as light
intensity, soil minerals, osmotic stresses (drought and salinity),
and seasonality (Waterman & Mole, 1989, 1994). Abiotic
environmental factors that constrain the production of secondary metabolite in plants indirectly influence the interactions
of plants with their biotic environment (Waterman & Mole,
1994). Therefore, in order to better understand the role of
emodin as a mediator of biotic interactions it is essential to
explore how its synthesis is influenced by abiotic factors.
Studies indicate that emodin levels in plants depend on
season and light intensity. The highest amount of total
anthraquinones (where approx. 50% was emodin) in the
leaves of Rheum undulatum in Europe was observed in springtime (April) followed by a continuous decrease during the
summer with the lowest anthraquinone amounts in late
summer (September) (Paneitz & Westendorf, 1999). Such a
seasonal pattern may reflect the trade-off between plant
development and defense (Waterman & Mole, 1989). Hence,
the level of emodin in R. undulatum may diminish in summer
when high metabolic activities, such as growing, flowering
and fruiting, utilize the limited plant resources. However, the
temporal pattern of emodin concentration in Rhamnus frangula bark in Europe showed three peaks (April, July–August
and November), and metabolic activities seem insufficient to
explain it (Kubiak, 1977).
Emodin (and total anthraquinones) content in suspension
cultures of Rhamnus purshiana was significantly raised by a
daily photoperiod of 12 h (Van den Berg et al., 1988). Similar
positive correlations between secondary metabolites and light
intensity emerged among individuals of the same species and
among organs of the same individual exposed to different
light intensities (Waterman & Mole, 1989). This phenotypic
response of the plant to increased light intensity is probably
due to increased carbon availability as predicted by the carbon/
nutrient hypothesis (Bryant et al., 1983).
Biological activities of emodin
Emodin (as well as physcion, chrysophanol, aloe-emodin and
rehin) forms the basis of a range of purgative anthraquinone
derivatives and from ancient times has been widely used as
a laxative compound (Evans, 1996; Bruneton, 1999). It is
believed that the presence of hydroxyl groups in position 1 and
8 of the aromatic ring system is essential for the purgative
action of the compound (Paneitz & Westendorf, 1999).
Because of its chemical structure, emodin glycosides (and
other anthraquinones) in mammals are carried unabsorbed to
the large intestine, where metabolism to the active aglycones
takes place by intestinal bacterial flora. The aglycone exerts
its laxative effect by damaging epithelial cells, which leads
directly and indirectly to changes in absorption, secretion and
motility (Mueller et al., 1999; Van den Gorkom et al., 1999).
Emodin also inhibits the ion transport (Cl−-channels) across
colon cells, contributing to the laxative effect (Rauwald, 1998).
Recent studies indicate that emodin exhibits numerous
other biological activities. It affects the immune system,
vasomotor system and metabolic processes (Table 2). Other
biological activities are anti-inflammatory, antimicroorganism
and antifeedant (Table 2). The molecular mechanisms underlying many of these biological effects remain either unknown
or controversial. Nevertheless, emodin has diversified modes
of action. For example, emodin increases the rate and force of
heart contractions probably through release of endogenous
catecholamines (Dwivedi et al., 1988), contributes to DNA
damage by inhibiting the catalytic activity of topoisomerase II
(Mueller et al., 1999), and induces muscle contractions by the
release of internal Ca2+ as a result of oxidation of the ryanodine receptor (Cheng & Kang, 1998). Many of the biological
activities of emodin are dose-dependent and different effective doses for a specific activity have been found in different
organisms (Boik, 1995). Of most relevance here, emodin has
many biological activities potentially mediating plant–plant,
plant–animal, plant–microorganism and plant–abiotic environment interactions.
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Table 2 Pharmacological and biological activities of emodin
Activity
Immuno-system
Immunosuppressive
Immunostimulant
Antiulcer
Mutagenicy and Genotoxicity
References
Huang et al. (1992)
Boik (1995)*
Goel et al. (1991)
Westendorf et al. (1990); Mueller & Stopper (1999); Van den
Gorkom et al. (1999)
Repair of UV-induced DNA damage
Antioxidant
Chang et al. (1999)
Yuan and Gao (1997); Yen et al. (2000)
Vasomotor System
Laxative
Diuretic
Vasorelaxive
Cardiac stimulant
Antitumor
Induces muscle contraction
Protein tyrosine kinase inhibitor
CNS (central nervous system) depressant
Release intra and extracellular free calcium in
brain cells
de Witte (1993); Rauwald (1998); Van den Gorkom et al. (1999)
Zhou & Chen (1988)
Huang et al. (1991)
Dwivedi et al. (1988)
Koyama et al. (1988); Su et al. (1995); Sun et al. (2000)
Cheng & Kang (1998)
Jayasuriya et al. (1992)
Dwivedi et al. (1988); Ram et al. (1994)
Lin & Jin (1995)
Metabolic responses
Hypolipidemic
Improves liver functions
Boik (1995)*
Yutao et al. (2000)
Anti microorganism activity
Antibacterial
Antifungal
Antiparasitic
Antiviral
Anke et al. (1980); Le Van (1984); Wang & Chung (1997)
Singh et al. (1992)
Wang (1993)
Kawai et al. (1984); Barnard et al. (1992)
Anti-inflammatory and Analgestic
Dwivedi et al. (1988); Chang et al. (1996)
Feeding deterrent
to phytophagous insects
to birds and small mammals
Trial & Dimond (1979)
Sherburne (1972); Wells et al. (1975)
*See References within.
Emodin–mediated interactions between plants
and the biotic environment
Feeding deterrent
The feeding-deterrent property is an important function
of emodin in mediating plant–animal interactions. Emodin
has a deterrent effect on a large spectrum of organisms from
invertebrates to vertebrates. In relatively low concentrations
of emodin, gypsy moth (Lymantria dispar) larvae reduced
feeding and prolonged development and with high concentrations a pronounced mortality occurred in 2–3 d (Trial &
Dimond, 1979). The mode of action of emodin as an insect
antifeedant is yet to be studied.
The effective feeding deterrent property of emodin to phytophagous insects was suggested as an explanation for the little
insect attack on Rhamnus alnifolia foliage (Trial & Dimond,
1979). The number of species of phytophagous insects on
introduced Rhamnus cathartica plants in Canada is much lower
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than on native plants in Europe (Malicky et al., 1970). This
may be indirect evidence of the importance of emodin (as well
as other anthraquinones), which occurs in R. cathartica
leaves (Maw, 1981), in the evolution of plant defense
against phytophagous insects. A long coevolution period
in Europe, but not in Canada, may enable the insects to
penetrate the defensive properties of R. cathartica. This is based
on the assumption that a long history of association between
certain groups of insects and plants caused a progressive accumulation of adaptations enabling insects to tolerate feeding
deterrents (Bernays & Chapman, 1994).
There are several indications that at certain levels emodin
is toxic and deters vertebrates. For example, yellow-vented
bulbuls (Pycnonotus xanthopygos) and house sparrows (Passer
domesticus) always preferred to feed on emodin-free bananamash diet than on diets that contained > 0.001% emodin
aglycone (f. wt) (Tsahar, 2001). Acute toxicity tests with
emodin that was given orally to redwing blackbirds (Agelaius
phoeniceusin) and starlings (Sternus vulgaris) revealed that
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LD50 (which estimates the dose of a substance needed to
kill half of a group) was > 100 mg kg−1 (Schafer et al., 1983).
The oral administration of emodin to 1-d-old cockerels
caused moderate diarrhoea and mortality within 5 d of
ingestion (LD50 = 3.7 mg kg−1, Wells et al., 1975). The
capacity of emodin to deter mammals is less well documented.
In feeding trials, captive white-footed mice (Peromyscus
leucopus) almost totally avoided emodin-containing food
(Sherburne, 1972).
The mode of action of emodin as a feeding deterrent on
birds and mammals is unknown. It is worth mentioning that
a closely related but naturally uncommon anthraquinone
(9,10 anthraquinone, Thomson, 1987) has been recognized
for many years as an avian deterrent (Avery et al., 1997). The
mode of action of this compound on birds is controversial.
Aversive taste was suggested by Thomson (1988) but refuted
by Avery et al. (1997). Either way, a slight difference in the
chemical structure of emodin may totally change its pharmacological activity, as is the case with many other secondary
metabolites (Waterman, 1992; Wink, 1999). Thus, it is
impossible to infer the mode of function of emodin from the
mode of function of 9,10-anthraquinone.
The antifeedant property of emodin may also have negative
effects on plant reproduction by deterring potential pollinators and seed dispersal agents. However, the antideterrent cost
of emodin for plant fitness has not been studied yet.
Allelopathy
Allelopathy is defined as the effect of one plant on another
plant through the release of a chemical compound in the
environment (Rice, 1995). Phenolics are among the major
substances that cause allelopathy (Inderjit, 1996). Emodin
at 10–100 mg l−1 inhibits the growth of roots and shoots of
sunflower (Helianthus annuus, LD50 = 45 mg l−1) and corn
(Zea mays var. everte, LD50 = 65 mg l−1) (Hasan, 1998). Inoue
et al. (1992) reported that emodin extracted from Polygonum
sachalinense exhibited inhibitory activities against the seedling
growth of lettuce (Lactuca sativa), green amaranth (Amaranthus
viridis) and timothy grass (Phleum pratense). The growth of
lettuce seedlings was severely inhibited at relatively low concentrations of emodin (50 ppm). Emodin > 100 ppm inhibited
root and hypocotyls growth or leaf sheath growth. It was also
argued that allelochemicals present in R. cathartica hinder
growth of many herbaceous woodland species surrounding
the trees by suppressing their germination (Boudreau & Wilson,
1992). Preliminary studies suggest that the dense shade
produced beneath the shrubs may contribute to this effect
(Taft & Solecki, 1990) but also that the fruit pulp may contain
allelopathic chemicals, including emodin, that leach from fallen
fruits (and leaves) into the soil and retard the growth of
competing plants (A. Krebsbach & C. Wilson, pers. comm.).
Inoue et al. (1992) speculated on the allelopathic mechanisms of emodin in S. sachalinense, based on data on emodin
concentrations in rhizomes, aerial part and in the soil.
The fresh rhizome with roots of P. sachalinense contained
158 mg kg−1 (f. wt) emodin and the aerial part contained
72 mg kg−1 (f. wt) emodin. Four months after defoliation, the
leaves still contained 213 mg kg−1 (d. wt) emodin. Furthermore,
emodin content of the soil was 55 mg kg−1 d. wt and was
sufficient to inhibit seedling growth of lettuce, green amaranth
and timothy grass. Inoue et al. (1992) suggested that emodin is
released from the rhizome (as glycoside or as aglycone) into the
soil and then the glycosides decompose to emodin aglycones,
which is the active form that exhibits seedling growth inhibition.
In addition, the litter of leaves is decomposed by physical or
biological processes that release emodin, which may affect
early seedling growth of nearby plants. Their results also
demonstrated that emodin is very stable in the ecosystem.
Allelochemicals that are released by plants may also
influence nutrient availability in the soil and hence indirectly
may affect plant survival (Appel, 1993; Inderjit & Dakshini,
1999). Schlesinger (1991) has suggested that plant phenolics
have the potential to influence soil nutrients and rates of
nutrient cycling, which ultimately influence plant growth.
Northup et al. (1999) have reviewed the different ways that
plant polyphenolics affect nutrient cycling and the implications for community structure. Indeed, emodin in the soil
directly decreased the Mn2+ availability, increased the Na+ and
K+ availability and indirectly decreased the PO43 – availability
(Inderjit & Nishimura, 1999). Therefore it is likely that emodin
that is released by plants adversely affects phosphate-requiring
species by depleting phosphate from the soil (Inderjit &
Nishimura, 1999). This is in accordance with the assertions of
Black (1973) that allelochemicals may cause imbalance in the
availability of nutrients in the soil and hence are likely to
influence plant growth and distribution.
Emodin may also indirectly affect soil microbial ecology as
a result of its effect on the composition of soil inorganic ions,
which may have a further influence on the availability of soil
nutrients (Inderjit & Dakshini, 1999). To date, the specific
contribution of the ion change caused by emodin on microbial activity remains unknown.
Antimicrobial activities
Many plant secondary metabolites have an allelopathic effect
on microorganisms (Rice, 1995). Surprisingly, it is unclear
whether phenols and other secondary metabolites have a role
in protecting plants from disease in vivo (Harborne, 1993).
But it has been demonstrated that anthraquinones, extracted
from different species of Aloe, exhibit antibacterial activity by
inhibition of nucleic acid synthesis in Bacillus subtilis (Levin
et al., 1988). For many years it has been known that emodin
has direct antibacterial activities (Anke et al., 1980; Kitanaka
& Takido, 1986). Emodin was found to inhibit nine soil
bacterial species (Arthrobacter globiformis, Chlorella pyrenoidosa,
Bacillus megaterium, 4 Rhizobium spp., and Azotobacter
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chroococcum) in vitro with minimal concentrations of 10–
200 µg ml−1 (Le Van, 1984). In the presence of emodin, the
cells of these bacteria developed aberrant morphological
forms, especially enhanced length (Le Van, 1984).
Emodin was also found to be an efficient antifungal toxin.
Emodin isolated from Rhamnus triquetra bark was highly
effective against spore germination of 17 tested fungi species
(including seven species of Alternaria and three species of
Fusarium, Singh et al., 1992). Less than 50% inhibition of the
spores of all fungi species was achieved at an emodin concentration of 500 µg ml−1 and maximum inhibition (up to 100%
in some species) was observed at an emodin concentration of
2000 µg ml−1 (Singh et al., 1992). Emodin was also highly
inhibitory against a pathogenic basidiomycete fungus, Fomes
annosus (Donnelly & Sharidan, 1986).
From the plant perspective, several direct and indirect nonexclusive ecological consequences of the antimicrobial activity
of emodin are possible. Because plant survival frequently
depends upon its disease resistance (Rice, 1984), emodin may
directly render the plant resistant to disease caused by microbial pathogens. It seems that emodin is a preinfection toxin
because it is consistently present in the plant (Tsahar, 2001),
and no study has indicated that it increases subsequent to
infection as an inducible defense. Singh et al. (1992) recently
suggested that the ability of some higher plants to resist fungal
pathogens depends on the presence of emodin along with
other chemicals in their tissues. In addition, because emodin
inhibits soil microorganisms, which may compete with the
plants for inorganic nutrients, emodin may indirectly
improve the competitive advantage of plants under some
circumstances (Rice, 1995; Schmidt & Ley, 1999). But, emodin
may also inhibit some mutualistic soil microorganisms, which
are beneficial for their host plants and therefore may reduce
plant fitness. This possible trade-off has not yet been studied.
To conclude, direct evidence of the ecological role of the
antimicrobial activity of emodin in plants in vivo is limited.
However, the in vitro studies and other circumstantial evidence indicate that the allelopathic properties of emodin may
directly and indirectly affect the survival and growth of plants.
Seed dispersal and germination
Recent studies has demonstrated that emodin might have an
impact at different stages of seed dispersal and facilitate plant
reproductive success (Tsahar, 2001; Tsahar et al., 2002). The
scope here is limited to fleshy-fruited species like Rhamnus
spp. as no study yet has investigated the effect of emodin on
other types of seed dispersal.
Unripe fleshy fruits are usually well protected chemically
against seed predators ( Janzen, 1983). Indeed, as demonstrated
in the Old World for R. alaternus and R. palestina (lycioides),
in the New World for R. cathartica, most bird species do not
consume the unripe fruits, probably because they contain
unpalatable chemicals (Sherburne, 1972; Maw, 1981; Izhaki,
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Review
1986; Tsahar, 2001). Captive American robins (Turdus
migratorius) and white-footed mice (Peromyscus leucopus) always
preferred ripe over unripe R. cathartica fruits (Sherburne,
1972). They significantly reduced feeding on ripe Prunus
virginiana and Rosa multiflora fruits that were coated with
emodin but readily accepted ripe fruits without emodin.
Furthermore, birds that were starved for 12 h consumed only
a few of the green fruits of R. cathartica (Sherburne, 1972).
American robins, catbirds (Dumetella carolinensis) and
redwings (Agelaius phoeniceus), which were forced to feed on
either Rhamnus green fruits or on gelatin capsules containing
50 µg−5 mg emodin, showed similar abnormal physiological
effects, such as diarrhoea (Sherburne, 1972). Many mammals
and birds have developed detoxification mechanisms that
enable them to cope with certain levels of dietary phenols
by conversion of the toxic compound in three metabolic
reactions: glucuronide synthesis, ethereal sulphate synthesis
and methylation (Williams, 1964). From the results described
above and the results on bulbuls and house sparrows (Tsahar,
2001), however, it seems that birds and small mammals are
unable to detoxify emodin efficiently, particularly when it is
present in high concentrations. Hence, emodin in unripe fruit
pulp protects against premature fruit consumption.
Secondary metabolites in fruit pulp are often broken down
during ripening, a process that is thought to promote
fruit consumption when the seeds are mature and ready for
dispersal ( Janzen, 1983; Garguillo & Stiles, 1993). A study on
Rhamnus alaternus indicates that although emodin concentration in the pulp decreases during ripening, it does not fully
disappear in ripe pulp (Tsahar et al., 2002). As emodin deters
potential seed dispersal agents, its presence in ripe fruits may
reduce the amount of fruits eaten and thus may have a negative effect on plant fitness. However, several nonexclusive
hypotheses may explain the adaptive significance of secondary metabolites in ripe fruits (Cipollini & Levey, 1997a,b;
Cipollini, 2000), some of which seem to be relevant in the
case of R. alaternus. Nevertheless, in contrast to the ‘protein
assimilation hypothesis’ holds that secondary metabolites
reduce fruit digestion and thus force the dispersal agents to
forage and deposit the seeds away from the parent tree (Izhaki
& Safriel, 1989; Izhaki, 1992), emodin actually improves bird
digestion ( Tsahar, 2001).
Insects and microorganisms seem to avoid not only the
foliage and green fruits of Rhamnus spp. but also the ripe
fruits. R. alaternus plants with relatively high emodin concentration in the pulp suffered less seed damage by insects and
microorganisms without reducing the total fruit removal
by seed dispersal agents than trees with lower concentrations
(Tsahar et al., 2002). These findings support the microbe/pest
specificity model, which states that negative effects of secondary
metabolites should be stronger on microbial and invertebrate
pests than on vertebrates, including dispersers (Cipollini,
2000). Despite the presence of certain amounts of emodin in
the ripe pulp, relatively large assemblages of avian frugivores
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consume the ripe fruits of many Rhamnus species and act as
seed dispersers (Herrera, 1984; Izhaki & Safriel, 1985; Tsahar,
2001; Izhaki, 2002). Frugivores may avoid the accumulation of secondary metabolites by consuming only a limited
number of fruits, thus shortening their foraging bouts on
the fruiting plants (Izhaki & Safriel, 1989, 1990b; Barnea
et al., 1993). This behavior ensures that the seeds would be
deposited away from parent plant and in small groups, thus
reducing plant-sibling and among-sibling competition
(‘attraction/repulsion’ hypothesis, Cipollini & Levey, 1997a;
Cipollini, 2000).
The laxative activity of emodin that was well documented
in humans ( Van den Gorkom, 1999) was also observed in
potential dispersal agents like small-mammals and birds
(Sherburne, 1972). Rapid passage of seeds through the
gut may ensure their viability. However, the ‘gut retention
hypothesis’ (Cipollini & Levey, 1997a) may not apply to
Rhamnus spp. because the seeds are encased in a moisturesensitive envelope that splits and ejects the seeds only after
exposure to dry air (Izhaki & Safriel, 1990a). Thus, the seeds
are fully protected during the passage through the gut and
germination is totally independent of gut characteristics of
the various dispersers (Izhaki & Safriel, 1990a; Barnea et al.,
1991). Short dispersal distance is the potentially disadvantageous consequence of rapid seed passage through the gut and
reflects the potential negative effect of emodin on plant fitness
(Cipollini & Levey, 1997a).
The direct effect of emodin on seed germination was
studied only for two plant species. The germination of control
sunflower (Helianthus annuus) seeds was 98% but emodin
treatments (50 and 100 mg l−1) inhibited the germination
to 76% and 55%, respectively (Hasan, 1998). However, the
same treatments did not affect the germination of corn (Zea
mays var. everte) seeds (Hasan, 1998). Furthermore, there is
some circumstantial evidence that emodin along with other
secondary metabolites may inhibit seed germination of other
plant species. Seeds of Rhamnus cathartica and R. alaternus
apparently will not germinate unless the fruit pulp is removed
either by hand or through seed passage in the digestive
tract of dispersal agents (Gourley & Howell, 1984; Barnea
et al., 1991). Eight other fleshy-fruited species, including
R. palaestinus, germinated within the intact fruits (Barnea
et al., 1991), but whether or not their pulp contain emodin
is unknown. Nevertheless, emodin (and other compounds)
in the pulp may inhibit germination of Rhamnus seeds,
depending upon concentration, either via direct chemical
inhibition as demonstrated for other seed species or by
controlling microenvironment factors such as light. Such an
autoallelopathy mechanism may prevent seed germination
within the fruits while they are either still attached to the
mother plant or on the ground beneath the mother plant.
In both cases the germination of undispersed seeds would be
detrimental to plant fitness and hence emodin may play an
important role as a seed germination inhibitor that allowed
germination only after the seeds are dispersed (Cipollini &
Levey, 1997a).
To conclude, emodin in unripe and ripe pulp may contribute to reduction of predispersal seed predation by insects
and microorganisms, prevention of dispersal of premature
seeds by vertebrates, dispersal of seeds away from the parent
plant and inhibition of seed germination within the fruit.
Although these functions have an adaptive value as they
increase plant fitness (Cipollini, 2000) some of them may
induce negative effects on plant fitness as well. Yet, the
adaptive approach to the presence of secondary metabolites
in fruits is controversial (Eriksson & Ehrlén, 1998) and the
possible trade-offs of their presence for plant reproduction
were not studied yet.
Antioxidant activity of emodin
The UV region of the solar radiation (c. 290–400 nm) is
potentially most damaging to higher plants (Lumsden, 1997).
The studies in the last two decades on the effectiveness of
naturally occurring compounds in plants as antioxidants
revealed that phenols have superior antioxidant capacity,
and it was argued that they may have evolved as a protection against the intense UV radiation endured by early
angiosperms (Swain, 1986; Cheeke, 1998). Emodin and
Cassia tora extracts that contain emodin do have a photoprotective function (Yen et al., 1998). Yuan and Gao (1997)
also reported on the antioxidant activity of emodin that
was shown to be a potent inhibitor of superoxide radicals.
The antioxidant activity of emodin probably depends on
scavenging hydroxyl radicals (Yen et al., 2000). Thus,
emodin, especially when occurring on the leaf surface, may
protect plants against harmful environmental effects of
excessive incident UV light.
Emodin is not alone
Because plants contain numerous secondary metabolites it is
important to recognize that organisms such as herbivores,
frugivores, granivores and pathogens do not interact with
chemicals in isolation. For example, herbivores that ingest
Rhamnus leaves simultaneously consume several other anthraquinones, tannins and flavonoids (Paya et al., 1986; Coskun,
1989, 1992; Abegaz & Peter, 1995) in addition to emodin.
Frugivores that feed on the fruit of Rhamnus prinoides actually
ingest emodin, physcion, rhamnazin, prinoidin, and many other
emodin-derived compounds (Abegaz et al., 1996). Likewise,
the roots of Rheum franzenbachii contain five anthraquinones
(emodin, chrysophanol, physcion, aloe-emodin and rhein
(Ma et al., 1989)).
Because of the complexity of chemical interactions in tissues
of living plants, a popular approach in chemical ecology has
been to quantify the total amount of all compounds that
belong to a single class (e.g. total phenolics, total alkaloids, etc.)
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Research review
and to associate them with a common biological property
(Rosenthal & Berenbaum, 1991; Berenbaum & Zangerl,
1992). Several of the anthraquinones, such as emodin, rhein,
chrysophanol and aloe emodin, indeed have common laxative
activity ( Van den Gorkom et al., 1999). Furthermore, the higher
laxative effect of a combination of anthraquinones was
explained by their synergistic effects (Rauwald, 1998). Yet,
individual anthraquinones also exhibit different biological
activities due to their different structures (Evans, 1996;
Bruneton, 1999). Minor differences in chemical structure can
lead to appreciable differences in biological activity because
the addition or reduction of a simple element may open new
molecular targets (Waterman, 1992; Waterman & Mole,
1994; Wink & Schimmer, 1999). Small differences among
anthraquinones, for instance, may determine the perception
and toxicity of different anthraquinones to different consumers, with potentially large effects for the plants (Bowers, 1988;
Wink & Schimmer, 1999). Therefore, quantifying the total
anthraquinones in plants may be sufficient to predict purgative effects but may not be sufficient to predict the full effects
of these compounds on plant fitness.
When a single compound has a profound effect on organisms, the appropriate approach is to isolate and quantify
this compound and to investigate its ecological attributes
(Berenbaum & Zangerl, 1992). Given the large and varied
effects of emodin, it seems valid to consider the distinct
attributes of it as an isolated compound. However, because
there is a potential for chemical interactions and synergism of
emodin with other secondary compounds, we should be
aware that its isolated ecological functions might not accurately
reflect its function within the chemical milieu of a plant.
The evolution of multifunctionality of emodin
Emodin is almost inevitably multifunctional in its effects. It
exhibits numerous biological activities; several of them are
thought to play significant ecological roles in the life of many
plant species by mediating their interactions with their biotic
and abiotic environment. But the multifunctional attribute of
emodin is probably an example of a much wider phenomenon
of ‘multipurpose defense’ secondary metabolites (Wink &
Schimmer, 1999). Although the many biological functions
attributable to emodin may in part reflect more intensive
study of this compound in comparison to other secondary
metabolites, it no doubt contradicts the assumption that
secondary metabolites are highly specific in their biological
functions (see also Cipollini, 2000).
Two nonexclusive hypotheses may explain the evolution of
multifunctionality of secondary metabolites. Firstly, plants
have to cope with a wide range of unpredictable biotic and
abiotic constraints, and selection should favor the production
of a single compound that exhibits the ability to protect the
plant against as many potential enemies and abiotic hazards as
possible ( Wink & Schimmer, 1999). The available data
© New Phytologist (2002) 155: 205–217 www.newphytologist.com
Review
suggest that in some species emodin is present in certain plant
parts all year long, and therefore it constantly protects these
parts against unpredictable environmental risks like herbivory
(both insects and vertebrates), pathogenic diseases, competition (allelopathy) and high light intensities. However, the data
presented in Table 1 suggests that in many species emodin has
not been found throughout all parts of the plant. This could
simply be a result of lack of emodin analyses in different plant
parts. But in case it represents the actual emodin distribution
among plant parts, an alternative interpretation of these data
would be that there are trade-offs in the production of emodin.
Thus, emodin presence in different plant parts at different
concentrations in different species reflects the diversity of
evolutionary trajectories and ecological conditions in which
emodin is found, and potentially, the diversity of different
adaptive functions it may have. Secondly, the defense strategy
of plants should be dynamic because the enemies usually
evolve resistance. Selection should maintain a single compound
as long as it is able to affect different molecular targets of the
same enemy simultaneously. The probability that the enemy
will evolve resistance against multitarget molecules is much
lower than for a single-target molecule and thus provides an
advantage for the plant in an arms race (Wink & Schimmer,
1999). The phenolic OH-groups enable anthraquinones to
interact with proteins by forming hydrogen and ionic bonds
(Wink & Schimmer, 1999). This explains the various interactions of emodin with enzymes, transporters, channels and
receptors. As these interactions are possible with every protein, we would expect multiple targets and multifunctional
activities (Wink & Schimmer, 1999). Thus, emodin in higher
plants may interfere with the same enemy through a variety of
molecular targets and mechanisms.
Although simultaneous multiple selection pressures may be
responsible for the production of multifunctional chemical
compounds, the conditions under which the chemical first
evolved may be different than the conditions that the plants
currently experience, such that the original selection pressures
that gave adaptive advantage to the new chemical are either a
subset of, or are even completely different from, the selection
pressures that currently maintain the adaptive advantage of
synthesis (Waterman, 1992; Cipollini, 2000). Furthermore,
emodin may have evolved in fungi and lichen independent
of its occurrence in higher plants. Although biotic and
abiotic factors may play a marginal role in the evolution of
the compound itself, the distribution and concentration of
emodin within different plants could be shaped by multiple
interactions of plants with their biotic and abiotic constraints.
Cooper-Driver & Bhattacharya (1998) suggested that a
compound, which arose early in the evolution of plants, might
gradually take on new functions. However, plant families that
currently contain emodin do not have monophyletic relationships and therefore we cannot preclude the possibility that
emodin arose independently on a number of occasions (Wink
& Waterman, 1999). In any case, selection would probably
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Research review
maintain emodin in higher plants as long as its benefit to
fitness outweighs its production cost.
Conclusions
Multiple functions of a single secondary metabolite have
fascinated many researchers. Cipollini (2000) called such
chemical compounds ‘jacks of all trades’ and Wink &
Schimmer, 1999) explained the evolution of such compounds
in terms of nature’s tendency ‘to catch as many flies with one
clap as possible’. I suggest that emodin is a case study
representing a much broader phenomenon among secondary
metabolites that have evolved as an integral part of the diverse
interactions between plants and their biotic and abiotic
environment. Nevertheless, most of the studies reviewed here
were not designed to examine the multifunctional approach.
Furthermore, there are many gaps in our understanding of
costs and benefits of emodin production and function. Future
studies should focus on the differential distribution of emodin
among plant parts and the biotic and abiotic factors that
are associated with emodin production in these parts. The
importance of basic abiotic factors such as seasonality and soil
minerals and water on emodin production are mostly
unknown. To advance our understanding of why plants do
and do not contain secondary metabolites in various tissues
we should also consider the trade-offs presented by their
production. Although this review reflects the lack of studies
that explored the potential cost of emodin production on
plant fitness, only by considering both costs and benefits in
the chemical multifunctionality puzzle will we be able to
develop predictive models that explain emodin occurrence.
My aim here has been to increase the awareness of chemical
multifunctionality in plant secondary metabolites and to
stimulate studies focusing on multiple ecological functions
of single secondary compounds in higher plants. Integrated
multidisciplinary efforts from ecologists, biochemists and
molecular biologists will be needed for this effort. Future
ecological studies of plant-secondary metabolites will be well
served by integrating multiple pathways by which metabolites
may mediate interactions of plants with their biotic and
abiotic environment.
Acknowledgements
I am grateful to William Setzer, Phyllis Coley, Michael Wink
and three anonymous reviewers for critical comments on
earlier versions of the manuscript, and Ella Tsahar, Jacob
Friedman, Emma Kvitnitsky, Irena Paloy, Zvia Shapira,
Moshik Inbar, Josef Katz, Doug Levey and Marty Cipollini
for their help in developing my ideas about the adaptive roles
of emodin. This research was supported by grants from the
University of Haifa and Oranim. The manuscript was written
while the author was on sabbatical leave at the Department of
Zoology, University of Florida.
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