Iridoids from Scrophularia Genus

Iridoids from Scrophularia Genus

Iridoids from Scrophularia Genus Javier de Santos Galindez, Lidia Fernández M atellano and A na M. D íaz Lanza* Laboratorio de Farmacognosia, D eparta...

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Iridoids from Scrophularia Genus Javier de Santos Galindez, Lidia Fernández M atellano and A na M. D íaz Lanza* Laboratorio de Farmacognosia, D epartam ento de Farmacologfa, Facultad de Farmacia, Universidad de Alcalä, 28871 Alcalä de Henares, M adrid, Espana. Fax: 918854660. E-mail: [email protected] * Author for correspondence and reprint requests Z. Naturforsch. 56c, 513-520 (2001); received February 6/March 12, 2001 Iridoid Gglycosides, Scrophularia, Scrophularia scorodonia We report here an updated summary about iridoid composition of a series from the genus Scrophularia which have been investigated until now from a phytochemistry point of view. In addition a list is included about iridoids isolated in our laboratory from different plant parts of Scrophularia scorodonia L.,which are com pared with iridoids from some species of the Scrophularia genus. The present study may serve as a current information to researchers working on phytochemistry and pharmacological aspects from the Scrophularia genus and possibly to serve as a new starting point for future investigations.

Iridoid glycosides such as harpagoside, aucuboside and harpagide are of particular interest to botanists because of their potential value in chemosystematics to elucidate phylogenetic relation­ ships (Bianco, 1990; Luczak and Swiatek, 1978). The Scrophularia genus is represented by more than 300 species. But only a few species have been investigated from a phytochemical and pharm aco­ logical point of view. We have now examined spe­ cies from genus Scrophularia which have been in­ vestigated from a phytochemical point of view, and report here the results of the literature search. In genus Scrophularia the following iridoid glyco­ sides have been found till now: Aucuboside, 6'cinnamoylaucuboside (scrophularioside), 1 0 -0 -ß glucosylaucuboside and scropheanoside I in: Scro­ phularia canina (Berdini et al., 1991), Scrophularia alata Gilib (Swiatek and Broda, 1967), Scrophula­ ria grossheimi (Akhmedov, 1970), Scrophularia nodosa (Weinges and von der Eltz, 1978), Scro­ phularia ningpoensis (Qian et al., 1992), Scrophu­ laria lateriflora (Swiatek et al., 1981), Scrophularia vernalis (Swiatek and Krzacek, 1976), Scrophula­ ria ilwensis (Calis et al., 1993) and Scrophularia koraiensis nakai (Pachaly et al., 1994) (Table I). Ester derivates of harpagide in: Scrophularia canina (Berdini et al., 1991), Scrophularia spicata (Zhang et al., 1992), Scrophularia ilwensis (Calis et al., 1993), Scrophularia buergeriana (Kitagawa et al., 1967), Scrophularia grossheimi (Akhmedov, 1970), Scrophularia nodosa (Weinges and von der Eltz, 1978), Scrophularia variegata (Babayan and 0939-5075/2001/0700-0513 $ 06.00

M natsakanyan, 1989), Scrophularia chrisantha (Babayan and M natsakanyan, 1989), Scrophularia ningpoensis (Quian et al., 1992; Ming et al., 1999), Scrophularia leucoclada (Saatov and Abdullaev, 1996), Scrophularia vernalis (Swiatek and Krzaczek, 1976) and Scrophularia koraiensis nakai (Pachaly et a l, 1994) (Table II). Acylated 6-O-aL-rhamnopyranosylcatalpol are common in genus Scrophularia: Scrophularia scopolii var. scopolii (Calis et al., 1988), Scrophularia nodosa (Weinges and von der Eltz, 1978), Scrophularia spicata (Zhang et a l, 1992), Scrophularia ilwensis (Calis et a l, 1993), Scrophularia auriculata (Giner et al., 1991; 1998), Scrophularia koelzii (Bhandari et al., 1992) and Scrophularia koraiensis nakai (Pachaly et al., 1994) (Table III). Catalpol, methylcatalpol, ajugol and laterioside were found only in some species : Scrophularia ningpoensis (Qian et a l, 1992), Scrophularia vernalis (Swiatek and Krzaczek, 1976), Scrophularia lateriflora (Swiatek et a l, 1981), Scrophularia ilwensis (Calis et a l, 1993). The presence of picroside I was detected only in one species, Scrophularia lateriflora (Swiatek et al., 1981) (Tables IV, V). In the course of a search for biologically active substances in S. scorodonia we have isolated sev­ eral iridoids from leaves and stems, flowers and roots from this species. For leaves and stems we have reported, bartsioside, aucuboside, harpagoside, 8-O-ds-cinnamoylharpagide, 8-O-acetyl-harpagide and one new iri­ doid 6-0-a-L-(3"-0-acetyl-2"-0-rram-cinnam oyl)-

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J. de Santos Galindez et al. ■Iridoids from Scrophularia Genus

rhamnopyranosylcatalpol (scorodioside) (Fernan­ dez M atellano et al., 1995a; Fernandez Matellano et al., 1995b). Different catalpol derivates have been isolated in this species: 6-0-a-L-(3"-0-fram' and cis pcoumaroyl)-rhamnopyranosylcatalpol and 6-O-aL-(2"-0-rra«5-p-coumaroyl)-rhamnopyranosylcatalpol (saccatoside) have been reported in flow­ ers; 6-0-a-L-(2"-0-acetyl-3",4"-0-di-frans-cinnamoyl)-rhamnopyranosylcatalpol (scropolioside B) and 6-O-methylcatalpol in roots from S. scorodonia (De Santos et al., 1998). It is of interest to compare the presence and dis­ tribution of some of these iridoids in different plant parts, because a different composition has been found in leaves, stems, flowers and roots (Ta­ ble VI). We have detected the presence of harpagide for the first time in leaves, stems and roots from S. scorodonia. In roots, we have isolated and identified different iridoids: bartsioside, aucubo-

side, harpagoside and 8-O-acetyl-harpagide. These com pounds have also been isolated from flowers of this species, except aucuboside. Scorodioside, the new iridoid glycoside isolated from leaves and stems, has also been identified in flowers. As shown in Table VI there is a different distribution between all plant parts. Identification and assigment of the isolated com pounds were perform ed on the basis of UV spectral data, !H and 13CNMR. Results and Discussion We have compiled a first listing of iridoids oc­ currence in Scrophularia genus (Table VII). From the distribution of iridoids listed it can be con­ cluded that the presence of aucuboside (52.9%), harpagide (47.05%), harpagoside (47.05%) and 8O-acetylharpagide (41.17%) is not rare in species of the genus, and we have also isolated these com­ pounds from Scrophularia scorodonia.

Table I. Aucuboside, scrophularioside, bartsioside and 10-0-ß-glucosylaucuboside.

C om pound

R

Species

R eference

A ucuboside

R 1=R 2=R 3= H R 4=O H

S. n odosa S. gross heim i S. lateriflora S. canina S. ningpoensis S. il w ens is S. scorodon ia S. alata S. vernalis

(W einges and von der Eltz, 1978) (A khm edov, 1970) (Swiatek et al., 1981) (B erdini et al., 1991) (Q uian et al., 1992) (Calis et al., 1993) (Fernandez et al., 1995 a) (Swiatek and Broda, 1967) (Swiatek and K rzaczek, 1976)

Scrophularioside

R 1=R 2=H R 3=C 6H sC H =C H -C O R 4=O H

S. lateriflora

(Sw iatek et al., 1981)

10-0-ß-G lu cosylaucub osid e

R 1=R 3=H R 2= ß -D -G L U C O S A R 4=O H

S. canina

(Berdini et al., 1991)

Bartsioside

R 1=R 2=R 3=R 4=H

S. scorodon ia

(Fernandez et al., 1995 a)

Scropheanoside I

R 1=R 2=R 3=H R4 = 4 " -0 -(p -0 C H ,-m -0 H -C hH v C H = C H -C 0 ) - ß -D -R H A M N O S A

S. koraiensis

(Pachaly et al., 1994)

J. de Santos Galindez et al. • Iridoids from Scrophularia Genus

515

Table II. Derivatives of harpagide.

Com pound

R

Species

R eference

Harpagide

R 1=H R 2=H

(W einges and von der Eltz, 1978) (A khm edov, 1970) (Babayan and M natsakanyan, 1989) (Babayan and M natsakanyan, 1989) (Q uian et al., 1992) (Calis et al., 1993) (Pachaly et al., 1994) (Saatov et al., 1996)

8-O -A cetyl-harpagide

R l=C H ^ -C O R 2=H

S. n odosa S. grossheim i S. variegata S. chrisantha S. ningpoensis S. ilwensis S. koraiensis S. leucoclada S. scorodonia S. n odosa S. vernalis S. variegata S. chrisantha S. canina S. ilwensis S. scorodonia S. leucoclada

(W einges and von der Eltz, 1978) (Swiatek and Krzaczek, 1976) (Babayan and M natsakanyan, 1989) (Babayan and M natsakanyan, 1989) (Berdini et al., 1991) (Calis et al., 1993) (Fernandez et al., 1995 a) (Saatov et al., 1996)

S. buergeriana S. variegata S. chrisantha

(Kitagawa et al., 1967) (Babayan and M natsakanyan, 1989) (Babayan and M natsakanyan, 1989)

S. buergeriana S. vernalis S. variegata S. chrisantha S. ningpoensis S. spicata S. koraiensis S. scorodonia S. scorodonia

(Kitagawa et al., 1967) (Swiatek and Krzaczek, 1976) (Babayan and M natsakanyan, 1989) (Babayan and M natsakanyan,,1989) (Quian et al., 1992) (Z hang et al., 1992) (Pachaly et al., 1994) (Fernandez et al., 1995 a) (Fernandez et al., 1995 b)

S. ningpoensis

(M ing et al., 1999)

S. ningpoensis

(M ing et al., 1999)

S. ningpoensis

(M ing et al., 1999)

8-0-(p-M ethoxycinnam oyl)harpagide

r i = c h , o -c 6h 4c h

= c h -c o

R 2=H

8-O-fra/zs-cinnamoylharpagide (harpagoside)

R l= C 6H s-C H =C H -C O R 2=H

8-0-czs-cinnamoyI-harpagide

R l= C 6H s-C H =C H -C O R 2=H R l= F eru loylR 2=H OH R l= C 6H ,-C H = C -C O R 2=H R 1=H R 2=d-galactopyranosyl

8-0-ds-feruloyl-harpagide

8-0-(2-hydroxy-cinnam oyl)harpagide 6-O -a-d-galactopyranosylharpagide

On the other hand, iridoids derived from aucuboside are rarer in the genus Scrophularia, they appear only in some species, such as scrophularioside in S. lateriflora , lO-O-ß-glucosylaucuboside in S. canina and scropheanoside I in S. koraiertsis (Table I). Moreover it is well known that species of Scro­ phularia contain catalpol derivates (Table III), but

some of this iridoids have been reported only in one species: koelzioside in S. koelzii, scropoliosides A and B in S. scopolii and S. auriculata , scrospioside B in S. spicata , scropheanoside II and 6-0-a-L-(2"-0-acetyl-3",4"-0-di-/?-methoxycinnamoyl) rhamnopyranosylcatalpol in S. koraiertsis and S.auriculata, respectively. Picroside I has been detected only in S. lateriflora and 6-0-(ß-D-xylo-

J. de Santos Galindez et al. • Iridoids from Serophularia Genus

516

Table III. Acylated derivates of 6-O-a-l-rhamnopyranosylcatalpol.

ORj /O R ,

Compound

R

Species

R eference

6-a-L -rham nopyranosyl-catalpol

R 1=R 2=R 3=H

S. nodosa

(W einges and von der Eltz, 1978)

6-0-a-L-(4"-0-acetyl-2", 3"-di-0-cinnam oyl)rh am nopyranosyl-catalpol (koelzioside)

R1 =R 2=C 6H ,-C H =C H -C O R 3=C H 3-CO-

S. koelzii

(Bhandari et al.. 1992)

6-0-a-L-(2", 4"-di-0-acetyl-3"-0-/7-methoxy-/ra/7scinnamoyl)-rhamnopyranosyl-catalpol (scropolioside A )

R l= R 3= C H ,-C O R2=CH30 - C 6H 4-C H =C H -C 0-

S. scopolii var scopolii S. auriculata

(Calis et al.. 1988)

6-0-a-L-(2"-0-acetyl-3'',4"-0-di-/rans-cinnamoyl)rhamnopyranosyl-catalpol (scropolioside B)

r i =c h

3- c o R 2=R 3=C 6H 5-CH=CH-CO-

6-0-a-L-(2'\ 4"-di-0-acetyl-3''-0-f/ww-cinnam oyl)rhamnopydranosyl-catalpol (scropolioside D )

R l= R 3 = C H 3-COR2=C6H 5-CH=CH-CO-

6-0-a-L-(2"-0-acetyl-3"-0-frans-cinnamoyl)rhamnopyranosyl-catalpol (scrospioside B)

r i = c h 3- c o R2=C 6H5-C H =C H -C O R3=H

Scropheanoside II

6-0-a-L-(2"-0-acetyl-3", 4"-0-di-/?-m ethoxicinnam oylrh am nopyranosyl)-catalpol

6-0-a-L-(3"-0-acetyl-2"-fra/M -cinnam oyl)rh am nopyranosyl-catalpol (scorodioside)

6-0-a-L-(2"-0-rranir-/7-coum aroyl)-rham nopyranosylcatalpol (saccatoside) 6-0-a-i--(3"0-trans and d s-p -coum arovl)rham nopyranosyl-catalpol

R 1=R2=H R 3=p-O C H 3-m -O H -C 6H 3C H =C H -C O -

(Giner et al.. 1988) (Calis et al.. 1988)

S. scopolii var. Scopolii. S. scorodonia

(D e Santos et al.. 1998)

S. ilwensis S. spicata S. koraiensis

(Calis et al., 1993) (Zhang et al., 1992) (Pachaly et al.. 1994)

S. spicata

(Zhang et al., 1992)

S. koraiensis

(Pachaly et al., 1994)

S. auriculata

(Giner et al., 1991)

S. Scorodonia

(Fernandez et al., 1995 b)

S. scorodonia

(D e Santos et al., 1998)

S. scorodonia

(D e Santos et al., 1998)

S.auriculata

(Giner et al., 1988)

R l= C H 3-COR 2 = R 3= p -C H ,0-C 6H 4-CH= CH-COR l=C „H s-CH =C H -C O R 2=C H 3-COR3=H R1 =H O -C 6H 4-C H =C H -C O R 2=R 3=H R 1=R 3=H R 2=H O -C 6H 4-CH=CH-CO-

6-0-a-L-(2", 3"-di-0-acetyl-4''-0-p-m ethoxy-cinnam oyl)R l= R 3 = C H 3-COrhamnopyranosyl-catalpol (scrovalentinoside) R2=C H 30 - C 6H 4-C H = C H -C 0-

pyranosyl) methylcatalpol is unique in S. ilwensis (Table IV). In S. scorodonia we have isolated three 6-O-a-Lrhamnopyranosylcatalpol derivates as saccatoside,

and 6-0-a-L-(3"-0 -trans and cis p-eoumaroyl)rhamnopyranosylcatalpol which have not been re­ ported previously in this genus. Also, bartsioside and S-O-c/s-cinnamoyl-harpagide are not present

J. de Santos Galindez et al. ■Iridoids from Scrophularia Genus

517

Table IV. Catalpol, methylcatalpol and picroside I.

C om pound

R

Species

R eference

C atalpol

R 1=R 2=R 3=R 4=H

S. lateriflora

(Sw iatek et al., 1981)

Picroside I

R 1=R 3=R 4==H R2=C 6H 5C H =C H -C O -

S. lateriflora

(Sw iatek et al., 1981)

6-M ethylcatalpol

R 1=R 2=R 4=H R 3=C H 3-

S. vernalis S. lateriflora S. ningpoensis S. scorodon ia

(Sw iatek and Krzaczek, 1976) (Swiatek et al., 1981) (Q uian et al., 1992) (D e Santos et al., 1998)

6-0-(ß-D -xylopiranosyl)m ethylcatalpol

R 1=R 2=H R 3= C H V R 4 = 0 -ß xylopiranosyl

S. il w ens is

(C alis et al., 1993)

Table V. Ajugol and laterioside. OH

6OR

CH3

? / ch 2oh

O

«k b z -

OH

Com pound

R

Species

Reference

Ajugol

R=H

S. lateriflora S. ilwensis

(Swiatek and Broda, 1967) (Weinges and von der Eltz, 1978)

Laterioside

R=C6H5-CH=CH-CO-

S. lateriflora

(Swiatek and Broda, 1967)

in Scrophularia genus, but we have isolated these com pounds in S. scorodonia. Of special interest is scorodioside, a new catal­ pol analog until now not reported as present in nature and which we have isolated from S. scoro­ donia.

Remarkably, catalpol, one of the most common iridoids, has not been found in the present investi­ gation. This compound has been isolated in the genus Scrophularia only in S. lateriflora (Ta­ ble IV).

With regard to the widespread occurrence of iri­ doids in members of genus Scrophularia, Scrophu­ laria scorodonia fits well into the genus, but the iridoid patterns were some different between this species and others species from this genus. As shown in Table VII S. scorodonia is the species which contains the major variety of iridoids, with 11 iridoids among 31 found until now in this genus and with an unequal distribution in different plant parts as shown in Table VI.

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J. de Santos Galindez et al. ■Iridoids from Scrophularia Genus

Table VI. Iridoids from Scrophularia scorodonia.

Scrophularia scorodonia

Iridoids Flowers

Leaves and stems

Roots

*

*

Aucuboside Bartsioside

*

*

*

Harpagide

*

*

*

8-O-acetyl-harpagide

*

*

*

Harpagoside

*

*

*

*

8-O-cis-cinnamoyl-harpagide

*

Scropolioside B Scorodioside

*

Saccatoside

*

6-0-a-L-(3"0-frans and cis-p-coumaroyl)rhamnopyranosyl-catalpol

*

*

*

6-Methylcatalpol

So, bartsioside, harpagide, 8-O-acetyl-harpagide and harpagoside, are present in all plant parts. Catalpol derivatives are predom inant in roots and flowers. Although scorodioside, the new iridoid isolated from S. scorodonia , is present in leaves, stems and flowers, it has not been detected in roots. Aucuboside, a common iridoid, was not found in flowers from this species, but it is present in leaves, stems and roots. Iridoids are present in a num ber of folk m edi­ cines used as bitter tonics, sedatives, antipyretics, cough medicines, remedies for wounds, skin disor­ ders and as hypotensives. Recently, intensive in­ vestigations on their bioactivity in general, and on their potential pharmacological activity in particu­ lar, have revealed that these compounds exhibit a wide range of bioactivity: cardiovascular, antihepatotoxic, choleretic, hypoglycemic and hypolip­ idemic, antiinflammatory, antispasmodic, antitu­ mor, antiviral, im m unom odulator and purgative activities (Ghisalberti, 1998). Although S. scorodonia has not been used in folk medicine, possible therapeutical properties of this species depend probably on a num ber of its constituents. Among them harpagoside and aucu­ boside should be m entioned as these compounds, they possess analgesic and antiinflam m atory activ­

ities (Recio et al., 1994). In addition, aucuboside is reported to exhibit antihepatotoxic, antispasmodic and antitumoral activities (Ghisalberti, 1998). The presence of 8-O-acetyl-harpagide may also be im­ portant, as the compound has shown antispas­ modic and vasoconstrictor activities (Breschi et al., 1992). Catalpol derivatives have shown to possess a lot of pharmacological properties, these type of compounds also exhibit antiinflammatory activity. Studies on antiinflammatory activity of these ca­ talpol derivatives and other iridoids isolated from S. scorodonia have exhibited an interesting activity (Bermejo et al., 1999).

Acknowledgem ents

This work was supported by: Acciones Integradas Spanish-French Rf. HF-211 & 98B; M. E. C. (Ministerio de Educaciön y Cultura); Ministerio de Sanidad (FISS Rf. 9471671); CAM (Com unidad Autönoma de Madrid Rf. C101/91); Proyectos Universidad de Alcala de Henares Ref. E006/2001. A G rant from Consejerfa de Educaciön y Cultura de Madrid, Comunidad Autönoma de Madrid (Conv. 1998).

J. de Santos Galindez et al. ■Iridoids from Scrophularia Genus

519

Table VII. Iridoids of the Scrophularia genus. 1

2

3

4

5

8

9

6

7

S. n odosa

*

*

*

S. gross he im i

*

*

S. lateriflora

*

S.canina

*

S.ningpoensis

*

*

S.ilwensis

*

*

*

S.scorodonia

*

*

*

*

S.alata

*

S. vernalis

*

*

*

*

*

*

*

*

*

*

*

*

S. chris ant a

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

* *

S.spicata

*

*

*

S.buergeriana

*

*

*

*

*

*

S .koelzii

*

S.scopolii \a r.sc o p o lii S.leucoclada

*

*

*

S. variegata

S.koraiensis

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

*

*

*

S.auriculata

(1) Aucuboside (2) Scrophularioside (3) lO-O-ß-glucosylaucuboside (4) Bartsioside (5) Scropheanoside I (6) Harpagide (7) 8-O-acetyl-harpagide (8) (p-Methoxycinnamoyl)-harpagide (9) Harpagoside (10) 8-O-cis-cinnamoyl-harpagide (11) 8-O-ferfuloyl-harpagide (12) 8-0-(2-hydroxy-cinnamoyl)harpagide

*

(13) 6-O-a-L-galactopyranosylharpagide (14) 6 - a - L - R h a m n o p y r a n o s y l- c a t a lp o l (15) Koelzioside (16) Scropolioside A (17) Scropolioside B (18) Scropolioside D (19) Scrospioside B (20) Scropheanoside II (21) 6-0-a-L-(2"-0-acetyl-3", 4"-0-dip-methoxicinnamoyl-rhamnopyranosyl)-catalpol (22) Scorodioside

*

*

(23) Saccatoside (24) 6 -0 -a-L -(3 "0 -trans and cis-p-

coumaroyl)-rhamnopyranosylcatalpol Screovalentinoside Catalpol Picroside I 6-Methylcatalpol

(25) (26) (27) (28) (29) 6-0-(ß-D-xylopiranosyl)-m ethyl catalpol (30) Ajugol (31) Laterioside

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J. de Santos Galindez et al. ■Iridoids from Scrophularia Genus

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