Furanocoumarins

The substances of this class are named after coumarin (Fig. 13.1), which was isolated in 1820 by Vogel from the tonka beans of the Dipteryx odorata Willd. tree. He named this substance after the common word, 'cumaru', for this tree in the native South American Tupi language. Coumarins are natural compounds with the 2H-benzopyran-2-one skeleton of coumarin as a characteristic feature. The vast majority have an oxygen atom at the seventh position, whereby coumarin itself is an exception. The coumarins have been divided into four classes. Coumarins with substitutions in the benzene ring are simple coumarins. An important member of this class in the biosynthetic pathway is the umbelliferone (Fig. 13.1). Simple coumarins are widespread in the plant kingdom and several hundreds of compounds have been isolated from more than 70 plant families. Furanocoumarins (also furocoumarins) are characterized by the addition of a fused furan ring. They are a typical feature of the Apiaceae, especially of the tribe Peucedaneae to which the genus Heracleum belongs (Molho et al., 1971). Their important contribution to

Fig. 13.1. Simple furanocoumarins (1 to 2), linear furanocoumarins (3 to 7) and angular fura-nocoumarins (8 to 11).

plant defence is well-documented (reviewed by Berenbaum and Zangerl, 1996). The other two classes are the pyranocoumarines, with a fused pyran ring, and the coumarins, which are substituted in the pyrone ring. Neither of these classes occur in the genus Heracleum (Nielsen, 1971). Here we concentrate on the furanocoumarins.

Two distinct types of furanocoumarins exist. In the linear type, the furane moiety is attached to the atoms C6 and C7 of the benzopyrane skeleton. Although linear coumarins occur sporadically in 15 families, they are ubiquitous only in the Apiaceae and Rutaceae (Murray et al., 1982). The angular furanocoumarins, in which the furane moiety is attached to the atoms C7 and C8, are much less widespread. They are commonly present only in the tribes of Apieae, Peucedaneae, Scandiceae and Dauceae (Nielsen, 1971) and are an outstanding feature in the genus Heracleum (Murray et al., 1982).

Furanocoumarins exert their toxicity in different ways. It is usually enhanced in the presence of UV-A light (320-370 nm, with a maximum at 340-360 nm) (Murray et al., 1982). The phototoxic effect relies on the ability of furanocoumarins to absorb a photon, leading to a high-energy triplet state. Coumarins are capable of binding to the pyrimidine base of nuclear DNA. Photo-activated linear furanocoumarins are able to form interstrand cross-links by reacting with an additional pyrimidine base. Even though monoadducts (i.e. binding to only one pyrimidin base) are able to inhibit DNA synthesis, to produce mutations, or to cause cell death, the effects are more pronounced when cross-link formations occur. In addition, furanocoumarins, in their excited energy stage, are capable of reacting with oxygen. This may result in the generation of singlet oxygen, hydroxy radicals or superoxide anion radicals. Furthermore, furanocoumarins are able to inhibit enzymes as well as to bind to proteins and to unsaturated fatty acids (Murray et al., 1982; Berenbaum and Zangerl, 1996, and references therein). An increased biosynthesis of furanocoumarins can be induced by a wide range of antagonists such as herbivorous insects, nematodes, fungi, bacteria and viruses (reviews in Murray et al., 1982; Berenbaum, 1991). The details of the biosynthetic pathway of furanocoumarins are described by Stanjek and Boland (1998).

H. mantegazzianum contains a particularly high concentration of furanocoumarins. Herde (2005) investigated the coumarin contents and composition of the fruits of 36 Apiaceae species. H. mantegazzianum had, with 3.92%, the second highest concentration of furanocoumarins after Ammi visnaga L., which had 4.34%. Although the furanocoumarin pattern of H. mantegazzianum has frequently been analysed (Table 13.1), the results are difficult to compare. Besides strong differences in the solubility of the compounds in different solvents and different extraction methods, coumarins are known to differ considerably between the plant organs (Molho et al., 1971; Knudson, 1983; Pira et al., 1989), plant populations (Zangerl and Berenbaum, 1990; Berenbaum and Zangerl, 1998), geographical areas (reviewed by Murray et al., 1982) and seasons (Knudson, 1983; Pira et al., 1989). Additionally, they are also influenced by abiotic factors such as nutrient availability or UV radiation (Zangerl and Berenbaum, 1987). Heracleum mantegazzianum contains the linear furanocoumarins bergapten, xanthotoxin, imperatorin, isopimpinellin and psoralen (Fig. 13.1). The angular furanocoumarin, angelicin (Fig. 13.1), contributes by far the highest proportion of coumarins in the fruits. Further angular furanocoumarins are pimpinellin, and especially in the roots, sphondin and isobergapten (Fig. 13.1). Ode et al. (2004) and Herde (2005) found that more than half of the total fura-nocoumarin content of H. mantegazzianum belonged to angular fura-nocoumarins. This high proportion is surprising because all other furanocoumarin-containing plants are unexceptionally dominated by linear furanocoumarins, and angular furanocoumarins usually comprise less than 10% (Berenbaum, 1991). Among the seven other species of the tribe Peucedaneae, including H. lanatum Michx. and H. sphondylium L. analysed

R IC

Furanocoumarin content in fruits (%)

Fig. 13.2. Furanocoumarin content and proportion of angular furanocoumarins in the fruits of nine species of the tribe Peucedaneae (Apiaceae). Data gathered from Herde (2005). The black circle represents H. mantegazzianum.

by Herde (2005), none showed such a high proportion of angular furanocoumarins (Fig. 13.2). It is necessary to mention at this point that both analyses were conducted with plant material obtained from the invaded range of H. mantegazzianum. However, Komissarenko et al. (1965) found similar high proportions of angular furanocoumarins in the roots of plants from Russia, even if the composition was different. Molho et al. (1971) found different furanocoumarin patterns in the fruits of giant hogweed specimens from three botanical gardens and suggested that the invasive plants represent a group of species and do not belong only to H. mantegazzianum (see Jahodova et al., Chapter 1, this volume).

In plants, furanocoumarins are primarily accumulated in oil canals and secretory ducts, which occur in all plant organs (Towers, 1980). These oil canals are associated with the vascular bundles. The amount of furanocoumarins, however, varies between different plant organs. In the Apiaceae, the highest amounts are usually located in the fruits, followed by the roots (Murray et al., 1982). Pira et al. (1989) found the concentrations to be high in the fruit, intermediate in the leaves and low in the stems of H. mantegazzianum. The concentrations varied strongly during the season and the maximal concentrations were found to be asynchronous to the seasonal solar radiation. Therefore they attributed this variation to the different biological phases of the plant. Leaf and root extracts strongly inhibited the growth of the yeast Candida albicans Berkhout, whereas extracts of stems or stalks showed lower toxicity (Knudson, 1983). Due to the enhanced toxicity in the presence of UV radiation, furanocoumarins should be more effective on the plant's surface. In the leaves of H. mantegazzianum, approximately 2% of the furanocoumarins are located on the surface (Zobel et al., 1990). Celery, Apium graveolens L., can respond to herbivory with an increased deposition of furanocoumarins on the leaf surface (Zobel and Glowniak, 1994; Stanjek et al., 1997).

Table 13.1. Summary of studies screening for coumarins in H. mantegazzianum. Qualitative analyses: Total furanocoumarin content of each study was set as 100%. Numbers indicate the percentage of a given compound, (x) = traces; semi-quantitative analysis: ++ = high levels, + = moderate levels, (+) = traces; qualitative analyses: X = present, (X) = traces.

Linear furanocoumarins

Angular furanocoumarins

Reference

Country

Plant organ

E

"(D CT

C .2

c

C

C

œ

lo

Q

D

C

'o

(D

u

£

£

CP

ra

"(D

C Œ

c o

O

ra

II

>

ra

ra

E

-C

<n

o

ra

X

>

-C

c

CP

CL

2

O

X

O

m

CL

<

CL

Reference

Country

Quantitative analyses:

Herde (2005)

Germany

Fruits

16.7

18.6

6.0

0.5

0.3 (x)

37.5

14.2

1.1

4.9

Ode et al. (2004)

Netherlands

Fruits

21.2

7.4

4.4

6.5

4.5

55.9

Komissarenko et al. (1965)

Caucasus

Roots

18.2

0.6

33.4

15.8

25.3

7.6

Semi-quantitative analyses:

Wawrzynowicz et al. (1989)

Fruits

tt

tt

t

t

t

t

Erdelmeier et al. (1985)

Germany

Leaves

w

t

(t)b

tt

(t)

(t)

(t)

Satsyperova and Komissarenko (1978) Caucasus

Fruits

tt

t

t a

t

+ b

t

t

tt

t a

+ c

t (t)

Qualitative analyses:

x d

Berenbaum (1981)

US

Seeds

x

x

x

(x)

x

(x) x

Berenbaum (1981)

US

Leaves

(x)

(x)

(x)

x d

Vanhaelen and Vanhaelen-Fastré (1974)

Roots

x

x

x

x

x

x

x

Molho et al. (1971)

Francee

Fruits

x

x

x

x

Molho et al. (1971)

Francee

Leaves

x

x

x

x

Molho et al. (1971)

Francee

Roots

x

x

x

(x)

(x)

x

x

x

Molho et al. (1971)

UK

Fruits

x

x

x

x

x

(x)

(x) x

x

Molho et al. (1971)

France'

Fruits

x

x

x

x

x

x

Beyrich (1968)

Fruits

x

x

x

x

x

x g

Karlsen et al. (1967)

Roots

x

x

x

x

x

x

x

x

Lee et al. (1966)

USA

Roots

x

x

x

x

x

x

a = Only traces in 2 of 4 analysed plant populations.

b = Absent in 2 of 4 analysed plant populations.

c = High content in 1 of 4 analysed plant populations.

d = Dihydro-furanocuoumarin-glycosides.

e = Plant material from the botanical garden Samoëns.

f = Plant material from the Laboratoire d'Ecologie Générale, Brunoy.

g = Chief component with approximately 50%.

a = Only traces in 2 of 4 analysed plant populations.

b = Absent in 2 of 4 analysed plant populations.

c = High content in 1 of 4 analysed plant populations.

d = Dihydro-furanocuoumarin-glycosides.

e = Plant material from the botanical garden Samoëns.

f = Plant material from the Laboratoire d'Ecologie Générale, Brunoy.

g = Chief component with approximately 50%.

Furanocoumarins protect against a wide variety of organisms including vertebrates, invertebrates, fungi and bacteria, as well as DNA and RNA viruses (Murray et al., 1982; Berenbaum, 1991). In arthropods, they can act as a feeding deterrent, leading to reduced growth or increased mortality (Berenbaum, 1991). Berenbaum and Zangerl (1996) reviewed studies on the biological activity of furanocoumarins and found that the degree of toxicity of the individual compounds does not follow a consistent order; the biological activity of a certain compound depends on the target organism and the feeding deterrence varies among taxa. Additionally, the importance of UV radiation is not consistent. In many studies, angelicin is less active compared to other fura-nocoumarins in the presence of UV radiation, but shows higher activity than other furanocoumarins in the absence of UV radiation. It is also difficult to state which of the various biological types of activity is most responsible for the toxic effects. Although it is generally assumed that the ability of fura-nocoumarins to bind to nuclear DNA is most responsible for the phototoxic reaction in human skin, there is some evidence that other mechanisms are also involved (Laskin et al., 1985). For herbivorous insects, evidence is accumulating that the inhibition of cytochrome P450 enzymes, which are involved in the detoxification of xenobiotics (see below), plays an important role (e.g. Neal and Wu, 1994). Synergistic effects of furanocoumarin mixtures have been reported from various studies. A combination of several furanocoumarins usually exhibits higher toxicity than each compound alone (Berenbaum and Zangerl, 1996; Calcagno et al., 2002).

The detoxification of furanocoumarins in specialized insects is mediated via cytochrome P450 monooxygenases (Ivie et al., 1983; Berenbaum, 2002). The resistance of insects is related to a faster and more efficient detoxification of this compound, whereby the induction level of P450 genes by increased enzymatic activity is of particular importance (Feyereisen, 1999; Li et al., 2004). Berenbaum and Zangerl (1993) found a strong synergistic effect of the linear xanthotoxin and the angular angelicin against the black swallowtail Papilio polyxenes F., a lepidopteran specialist feeding on Apiaceae. The toxic effect was related to a reduced catabolism rate of both compounds mediated by angelicin. This resulted in enhanced levels of unmetabolized xanthotoxin. Likewise synergistic effects were found in Depressaria radiella (Goeze) (syn. D. pastinacella) (Nitao, 1989). Instead of detoxification, insects can avoid contact with toxic substances. The two aphid species, Aphis heraclella Davis and Cavariella pastinacea L., did not contain or excrete xanthotoxin after feeding on Heracleum lanatum (Camm et al., 1976). The authors concluded that this compound is not translocated in the phloem. Berenbaum (1978) suggested that the spinning of a web on flower heads or the rolling of leaves might have been developed to avoid UV radiation. Furanocoumarins can also act on a multitrophic level. Larvae of D. radiella are less commonly parasitized by the parasitic wasp Copidosoma sosares (Walker) when feeding on H. mantegazzianum plants with a high amount of xanthotoxin (Ode et al., 2004).

The high amount of furanocoumarins in the roots of many Apiaceae is still not understood. Certainly there are some biological activities in the absence of

UV light, especially against microorganisms. However, high contents of fura-nocoumarins within the Apiaceae are, as a rule, associated with plants occurring in light-exposed habitats and are less pronounced in woodland species (Berenbaum, 1981), which underlines the importance of light.

Was this article helpful?

0 0

Post a comment