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A phenylethanoid glycoside and flavonoids from Phlomis crinita (Cav.) (Lamiaceae)
Biochemical Systematics and Ecology 33 (2005) 813e816 www.elsevier.com/locate/biochemsyseco
A phenylethanoid glycoside and flavonoids from Phlomis crinita (Cav.) (Lamiaceae) A. Kabouche a, Z. Kabouche a,*, E. Seguin b, F. Tillequin c, C. Bruneau d a
Laboratoire d’Obtention de Substances The´rapeutiques (LOST), Faculte´ des Sciences, Universite´ Mentouri e Constantine, Campus Chaabet Ersas, 25000 Constantine, Algeria b Equipe Pharmacomodulation d’antitumoraux d’origine naturelle et synthe´tique, Laboratoire de Pharmacognosie, Faculte´ de Pharmacie, 22, Boulevard Gambetta, F-76183 Rouen Cedex 1, France c Laboratoire de Pharmacognosie de l’Universite´ Rene´ Descartes, U.M.R./C.N.R.S. N 8638, Faculte´ des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l’Observatoire, F-75006 Paris, France d Universite´ de Rennes 1, U.M.R./C.N.R.S. N 6509, Campus de Beaulieu, 35042 Rennes cedex, France Received 6 January 2005; accepted 31 January 2005
Keywords: Phlomis crinita; Lamiaceae; Flavonoids; Phenylethanoid glycoside; Verbascoside; Chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside
1. Subject and source Phlomis crinita (Cav.) was collected from Djebel El-Ouach, Constantine, Algeria at an altitude of 800 m in May 2000. The plant material was authenticated by Mr. Kamel Kabouche (Constantine) and a voucher specimen (LOST/ZKAK Pc 05/ 00) was deposited at the Herbarium, Faculty of Sciences, University MentouriConstantine and at the Muse´e Botanique de la Ville d’Angers, France (ANG-NA-01).
* Corresponding author. Tel./fax: C213 31 81 88 59. E-mail address: [email protected] (Z. Kabouche). 0305-1978/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.bse.2005.01.006
814
A. Kabouche et al. / Biochemical Systematics and Ecology 33 (2005) 813e816
2. Previous work No reports.
3. Present study As part of our phytochemical studies on medicinal plants growing in North Algeria (Kabouche et al., 2003; Benkiki et al., 2003), we report here from P. crinita (fam. Lamiaceae) a phenylethanoid glycoside, verbascoside (1) and three known flavonoids namely, luteolin (2), luteolin 7-b-D-glucopyranoside (3) and chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside (4) which is reported for the second time from a Phlomis species. It was earlier isolated from Phlomis lychitis (Toma´s et al., 1986) but some protons are not well assigned. The corrected NMR elucidation of the compound (4) is reported here and the corrected NMR values and other spectral data are given below. Air-dried and powdered aerial parts of P. crinita were macerated in a methanolic solution (70%). The residue was filtered, concentrated, then successively extracted with petroleum ether, dichloromethane, ethyl acetate and n-butanol. The ethyl acetate extract was concentrated and column chromatographed on silica gel G-60 with EtOAcecyclohexane. The major fraction was concentrated and purified by prep. TLC on silica gel 60F with a gradient of EtOAcecyclohexane with increasing polarity leading to apigenin, luteolin and luteolin 7-O-b-D-glucopyranoside which spectral data (UV, MS, NMR) were in accordance with the literature data. The butanolic extract was concentrated and column chromatographed on silica gel G-60 with a gradient of EtOAceMeOH with increasing polarity leading to verbascoside (1) and chrysoeriol 7-(3$-p-E-coumaroyl)glucopyranoside (4). The verbascoside (1) structure was identified according to the literature data (Andary et al., 1982) and its structure was confirmed by its peracetylation using acetic anhydride in the presence of anhydrous pyridine affording the nonacetyl verbascoside (5) as an amorphous powder [a]20 D Z ÿ56 (c Z 1, CHCl3) which spectral data were in accordance with the literature. The flavonoids were purified on Sephadex LH-20. For each flavonoid, UV analysis was carried out in several systems according to the literature procedure (Mabry et al., 1970; Markham, 1982). 1H NMR (d [ppm], J [Hz]) and 13C NMR spectra were recorded at 300 MHz and 75 MHz, respectively, using a Bruker AC-300 spectrometer. Multiple-pulse 2D NMR experiments (1He1H COSY, 1He1H NOESY, 13Ce1H HETCOR, and 13Ce1H COLOC) were performed using standard Bruker microprograms. Column chromatographies were carried out with silica gel 20e45 mm. Flash column chromatographies were conducted using silica gel 60 Merck (35e70 mm). The proton NMR spectrum of the compound (4) showed similar signals reported in the structure elucidation of chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside isolated from Phlomis lychnitis (Toma´s et al., 1986) except in the attribution of the signal of H-3 which appeared at 7.0 ppm, as reported from other similar structures, instead of 5.925 ppm reported from P. lychnitis. We must also notice the
815
A. Kabouche et al. / Biochemical Systematics and Ecology 33 (2005) 813e816
second error observed in the previous paper where the H-3#$/H-5#$ and the H-2#$/H6#$ signals belonging to the caffeic moiety are inverted. In addition to 1H NMR and 13 C NMR, the 2D NMR experiments 13Ce1H permitted us to confirm the resonance of the proton H-3 as a singlet at 7.0 ppm. The ESC mass spectrum of the compound showed a molecular ion at m/z 609 [M C H]C corresponding to the molecular formula C31H28O13 chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside (4). OMe 3'''
HO
H
2'''
4'''
4"
6"
HO
5"
O 3"
5'''
6'''
H
O
3'
HO O
8
O
2"
OH
7
O
1 5' 2
1" 4
6
OH
4'
2'
6'
3
5
OH
O
UV (MeOH) lmax (nm) 270, 294sh, 318, 355sh; IR (KBr) nmax 2980, 2934, 1732, 1650, 1452, 1375, 1290, 1169, 1128, 1080, 1035, 1013 cmÿ1; 1H NMR (400 MHz, DMSO-d6): 3.46 (1H, t, J Z 9 Hz, H-4$); 3.50 (1H, dd, J Z 9.4 Hz, H-2$); 3.53 (1H, m, H-6$B); 3.62 (1H, m, H-5$); 3.72 (1H, dd, m, H-6$A); 3.85 (3H, s, OCH3); 5.06 (1H, d, J Z 9.4 Hz, H-3$); 5.25 (1H, t, J Z 7.8 Hz, H-1$); 6.42 (1H, d, J Z 15.7 Hz, CHCO); 6.46 (1H, d, J Z 2 Hz, H-6); 6.79 (1H, d, J Z 8.6 Hz, H-5#); 6.81 (2H, d, J Z 9.0 Hz, H-3#$ and H-5#$); 6.86% (1H, d, J Z 2 Hz, H-8); 7.0 (1H, s, H-3); 7.48 (1H, d, J Z 2. Hz, H-2#); 7.55 (1H, d, J Z 2 Hz, H-6#); 7.56 (2H, d, J Z 9.0 Hz, H-2#$ and H-6#$); 7.58 (1H, d, J Z 15.7 Hz, CH]C); MS (ESC): 609 [M C H]C, 579[M C HeOCH3]C, 301[M C H-p-coumaroylglucopyranoside]C corresponding to the molecular formula C31H28O13.
4. Chemotaxonomic significance The genus Phlomis (Lamiaceae) comprises some 250 species and subspecies widely distributed in China (60 species), Ex-URSS (54 species) and Turkey (45 species). Four species grow in Northern Algeria: a Mediterranean species, Phlomis herba-venti and three endemic species namely, Phlomis bovei, Phlomis caballeroi and P. crinita (Quezel and Santa, 1963). Its the first time that an Algerian Phlomis species is studied. The most interesting isolated flavonoid from this endemic species, chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside is isolated for the second time from a Phlomis species, it was earlier reported from P. lychnitis (Toma´s et al., 1986) but flavonoids p-coumaroyl glucosides, in general, appear to be characteristic of the genus Phlomis and also of some related genus such as Ballota, Marrubium,
816
A. Kabouche et al. / Biochemical Systematics and Ecology 33 (2005) 813e816
Sideritis, Galeopsis and Stachys (Toma´s-Barbera´n et al., 1992). The genus Phlomis seems to be rich in phenylethanoid glycosides e.g. verbascoside which has been reported from 14 species namely, Phlomis monocephala and Phlomis carica (Yalcin et al., 2003), Phlomis sintenisii (Calis et al., 2002), Phlomis chimerae (Ersoz et al., 2001a), Phlomis grandiflora var. fimbrilligera and Phlomis fruticosa (Ersoz et al., 2002a), Phlomis sieheana (Ersoz et al., 2002b), Phlomis longifolia var. longifolia (Ersoz et al., 2001b), Phlomis tuberosa L. (Ersoz et al., 2001c), Phlomis samia (Kyriakopoulou et al., 2001), Phlomis aurea (Kamel et al., 2000), Phlomis bourgaei Boiss. (Harput et al., 1999), Phlomis grandiflora var. grandiflora (Takeda et al., 1999) and Phlomis armeniaca (Saracoglu et al., 1995).
Acknowledgments The authors would like to thank the National Health Research Agency, Oran Algeria (A.N.D.R.S) for the financial support and Dr. Rachid Touzani (Ottawa, Canada) for helpful bibliographical complements.
References Andary, C., Wylde, R., Laffite, C., Privat, G., Winternitz, F., 1982. Phytochemistry 21, 1123. Benkiki, N., Kabouche, Z., Tillequin, F., Ve´rite´, P., Chosson, E., Seguin, E., 2003. Z. Naturforsch. C 58c (9/10), 655. Calis, I., Kirmizibekmez, H., Ersoz, T., Saracoglu, I., Donmez, Ali A., Mitova, M., Handjieva, N., Popov, S., 2002. Turk. Acta Pharm. Turc. 44 (3), 195. Ersoz, T., Saracoglu, I., Harput, U.S., Calis, I., Donmez, Ali A., 2002a. Turk. J. Chem. 26 (2), 171. Ersoz, T., Harput, U.S., Calis, I., Donmez, Ali A., 2002b. Turk. J. Chem. 26 (1), 1. Ersoz, T., Saracoglu, I., Kirmizibekmez, H., Yalcin, F.N., Harput, U.S., Donmez, Ali A., Calis, I., 2001a. Hacettepe Univ. Eczaci. Fak. Derg. 21 (1), 23. Ersoz, T., Schuhly, W., Popov, S., Handjieva, N., Sticher, O., Calis, I., 2001b. Nat. Prod. Lett. 15 (5), 345. Ersoz, T., Ivancheva, S., Akbay, P., Sticher, O., Calis, I., 2001c. Z. Naturforsch. C 56 (9/10), 695. Harput, U.S., Saracoglu, I., Calis, I., 1999. Hacettepe Univ. Eczaci. Fak. Derg. 19 (1), 1. Kabouche, Z., Benkiki, N., Seguin, E., Bruneau, C., 2003. Fitoterapia 74, 194. Kamel, M.S., Mohamed, K.M., Hassanean, H.A., Ohtani, K., Kasai, R., Yamasaki, K., 2000. Phytochemistry 55 (4), 353. Kyriakopoulou, I., Magiatis, P., Skaltsounis, A.-L., Aligiannis, N., Harvala, C., 2001. J. Nat. Prod. 64 (8), 1095. Mabry, T.J., Markham, K.R., Thomas, M.B., 1970. The Systematic Identification of Flavonoids. Springer, New York. Markham, K.R., 1982. Techniques of Flavonoid Identification. Academic Press, London. Quezel, P., Santa, S., 1963. Nouvelle flore de l’Alge´rie et des Re´gions De´sertiques et Me´ridionales, Tome II. Editions CNRS, Paris (in French). Saracoglu, I., Inoue, M., Calis, I., Ogihara, Y., 1995. Biol. Pharm. Bull. 18 (10), 1396. Takeda, Y., Kinugawa, M., Masuda, T., Honda, G., Otsuka, H., Sezik, E., Yesilada, E., 1999. Phytochemistry 51 (2), 323. Toma´s-Barbera´n, F.A., Gil, M.I., Ferreres, F., Toma´s-Lorente, F., 1992. Phytochemistry 31 (9), 3097. Toma´s, F., Nieto, J.L., Barbera´n, F.A.T., Ferreres, F., 1986. Phytochemistry 25, 1253. Yalcin, F.N., Ersoez, T., Akbay, P., Calis, I., Doenmez, Ali A., Sticher, O., 2003. Turk. J. Chem. 27 (3), 295.
A phenylethanoid glycoside and flavonoids from Phlomis crinita (Cav.) (Lamiaceae) A. Kabouche a, Z. Kabouche a,*, E. Seguin b, F. Tillequin c, C. Bruneau d a
Laboratoire d’Obtention de Substances The´rapeutiques (LOST), Faculte´ des Sciences, Universite´ Mentouri e Constantine, Campus Chaabet Ersas, 25000 Constantine, Algeria b Equipe Pharmacomodulation d’antitumoraux d’origine naturelle et synthe´tique, Laboratoire de Pharmacognosie, Faculte´ de Pharmacie, 22, Boulevard Gambetta, F-76183 Rouen Cedex 1, France c Laboratoire de Pharmacognosie de l’Universite´ Rene´ Descartes, U.M.R./C.N.R.S. N 8638, Faculte´ des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l’Observatoire, F-75006 Paris, France d Universite´ de Rennes 1, U.M.R./C.N.R.S. N 6509, Campus de Beaulieu, 35042 Rennes cedex, France Received 6 January 2005; accepted 31 January 2005
Keywords: Phlomis crinita; Lamiaceae; Flavonoids; Phenylethanoid glycoside; Verbascoside; Chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside
1. Subject and source Phlomis crinita (Cav.) was collected from Djebel El-Ouach, Constantine, Algeria at an altitude of 800 m in May 2000. The plant material was authenticated by Mr. Kamel Kabouche (Constantine) and a voucher specimen (LOST/ZKAK Pc 05/ 00) was deposited at the Herbarium, Faculty of Sciences, University MentouriConstantine and at the Muse´e Botanique de la Ville d’Angers, France (ANG-NA-01).
* Corresponding author. Tel./fax: C213 31 81 88 59. E-mail address: [email protected] (Z. Kabouche). 0305-1978/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.bse.2005.01.006
814
A. Kabouche et al. / Biochemical Systematics and Ecology 33 (2005) 813e816
2. Previous work No reports.
3. Present study As part of our phytochemical studies on medicinal plants growing in North Algeria (Kabouche et al., 2003; Benkiki et al., 2003), we report here from P. crinita (fam. Lamiaceae) a phenylethanoid glycoside, verbascoside (1) and three known flavonoids namely, luteolin (2), luteolin 7-b-D-glucopyranoside (3) and chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside (4) which is reported for the second time from a Phlomis species. It was earlier isolated from Phlomis lychitis (Toma´s et al., 1986) but some protons are not well assigned. The corrected NMR elucidation of the compound (4) is reported here and the corrected NMR values and other spectral data are given below. Air-dried and powdered aerial parts of P. crinita were macerated in a methanolic solution (70%). The residue was filtered, concentrated, then successively extracted with petroleum ether, dichloromethane, ethyl acetate and n-butanol. The ethyl acetate extract was concentrated and column chromatographed on silica gel G-60 with EtOAcecyclohexane. The major fraction was concentrated and purified by prep. TLC on silica gel 60F with a gradient of EtOAcecyclohexane with increasing polarity leading to apigenin, luteolin and luteolin 7-O-b-D-glucopyranoside which spectral data (UV, MS, NMR) were in accordance with the literature data. The butanolic extract was concentrated and column chromatographed on silica gel G-60 with a gradient of EtOAceMeOH with increasing polarity leading to verbascoside (1) and chrysoeriol 7-(3$-p-E-coumaroyl)glucopyranoside (4). The verbascoside (1) structure was identified according to the literature data (Andary et al., 1982) and its structure was confirmed by its peracetylation using acetic anhydride in the presence of anhydrous pyridine affording the nonacetyl verbascoside (5) as an amorphous powder [a]20 D Z ÿ56 (c Z 1, CHCl3) which spectral data were in accordance with the literature. The flavonoids were purified on Sephadex LH-20. For each flavonoid, UV analysis was carried out in several systems according to the literature procedure (Mabry et al., 1970; Markham, 1982). 1H NMR (d [ppm], J [Hz]) and 13C NMR spectra were recorded at 300 MHz and 75 MHz, respectively, using a Bruker AC-300 spectrometer. Multiple-pulse 2D NMR experiments (1He1H COSY, 1He1H NOESY, 13Ce1H HETCOR, and 13Ce1H COLOC) were performed using standard Bruker microprograms. Column chromatographies were carried out with silica gel 20e45 mm. Flash column chromatographies were conducted using silica gel 60 Merck (35e70 mm). The proton NMR spectrum of the compound (4) showed similar signals reported in the structure elucidation of chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside isolated from Phlomis lychnitis (Toma´s et al., 1986) except in the attribution of the signal of H-3 which appeared at 7.0 ppm, as reported from other similar structures, instead of 5.925 ppm reported from P. lychnitis. We must also notice the
815
A. Kabouche et al. / Biochemical Systematics and Ecology 33 (2005) 813e816
second error observed in the previous paper where the H-3#$/H-5#$ and the H-2#$/H6#$ signals belonging to the caffeic moiety are inverted. In addition to 1H NMR and 13 C NMR, the 2D NMR experiments 13Ce1H permitted us to confirm the resonance of the proton H-3 as a singlet at 7.0 ppm. The ESC mass spectrum of the compound showed a molecular ion at m/z 609 [M C H]C corresponding to the molecular formula C31H28O13 chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside (4). OMe 3'''
HO
H
2'''
4'''
4"
6"
HO
5"
O 3"
5'''
6'''
H
O
3'
HO O
8
O
2"
OH
7
O
1 5' 2
1" 4
6
OH
4'
2'
6'
3
5
OH
O
UV (MeOH) lmax (nm) 270, 294sh, 318, 355sh; IR (KBr) nmax 2980, 2934, 1732, 1650, 1452, 1375, 1290, 1169, 1128, 1080, 1035, 1013 cmÿ1; 1H NMR (400 MHz, DMSO-d6): 3.46 (1H, t, J Z 9 Hz, H-4$); 3.50 (1H, dd, J Z 9.4 Hz, H-2$); 3.53 (1H, m, H-6$B); 3.62 (1H, m, H-5$); 3.72 (1H, dd, m, H-6$A); 3.85 (3H, s, OCH3); 5.06 (1H, d, J Z 9.4 Hz, H-3$); 5.25 (1H, t, J Z 7.8 Hz, H-1$); 6.42 (1H, d, J Z 15.7 Hz, CHCO); 6.46 (1H, d, J Z 2 Hz, H-6); 6.79 (1H, d, J Z 8.6 Hz, H-5#); 6.81 (2H, d, J Z 9.0 Hz, H-3#$ and H-5#$); 6.86% (1H, d, J Z 2 Hz, H-8); 7.0 (1H, s, H-3); 7.48 (1H, d, J Z 2. Hz, H-2#); 7.55 (1H, d, J Z 2 Hz, H-6#); 7.56 (2H, d, J Z 9.0 Hz, H-2#$ and H-6#$); 7.58 (1H, d, J Z 15.7 Hz, CH]C); MS (ESC): 609 [M C H]C, 579[M C HeOCH3]C, 301[M C H-p-coumaroylglucopyranoside]C corresponding to the molecular formula C31H28O13.
4. Chemotaxonomic significance The genus Phlomis (Lamiaceae) comprises some 250 species and subspecies widely distributed in China (60 species), Ex-URSS (54 species) and Turkey (45 species). Four species grow in Northern Algeria: a Mediterranean species, Phlomis herba-venti and three endemic species namely, Phlomis bovei, Phlomis caballeroi and P. crinita (Quezel and Santa, 1963). Its the first time that an Algerian Phlomis species is studied. The most interesting isolated flavonoid from this endemic species, chrysoeriol 7-(3$-p-E-coumaroyl)-b-D-glucopyranoside is isolated for the second time from a Phlomis species, it was earlier reported from P. lychnitis (Toma´s et al., 1986) but flavonoids p-coumaroyl glucosides, in general, appear to be characteristic of the genus Phlomis and also of some related genus such as Ballota, Marrubium,
816
A. Kabouche et al. / Biochemical Systematics and Ecology 33 (2005) 813e816
Sideritis, Galeopsis and Stachys (Toma´s-Barbera´n et al., 1992). The genus Phlomis seems to be rich in phenylethanoid glycosides e.g. verbascoside which has been reported from 14 species namely, Phlomis monocephala and Phlomis carica (Yalcin et al., 2003), Phlomis sintenisii (Calis et al., 2002), Phlomis chimerae (Ersoz et al., 2001a), Phlomis grandiflora var. fimbrilligera and Phlomis fruticosa (Ersoz et al., 2002a), Phlomis sieheana (Ersoz et al., 2002b), Phlomis longifolia var. longifolia (Ersoz et al., 2001b), Phlomis tuberosa L. (Ersoz et al., 2001c), Phlomis samia (Kyriakopoulou et al., 2001), Phlomis aurea (Kamel et al., 2000), Phlomis bourgaei Boiss. (Harput et al., 1999), Phlomis grandiflora var. grandiflora (Takeda et al., 1999) and Phlomis armeniaca (Saracoglu et al., 1995).
Acknowledgments The authors would like to thank the National Health Research Agency, Oran Algeria (A.N.D.R.S) for the financial support and Dr. Rachid Touzani (Ottawa, Canada) for helpful bibliographical complements.
References Andary, C., Wylde, R., Laffite, C., Privat, G., Winternitz, F., 1982. Phytochemistry 21, 1123. Benkiki, N., Kabouche, Z., Tillequin, F., Ve´rite´, P., Chosson, E., Seguin, E., 2003. Z. Naturforsch. C 58c (9/10), 655. Calis, I., Kirmizibekmez, H., Ersoz, T., Saracoglu, I., Donmez, Ali A., Mitova, M., Handjieva, N., Popov, S., 2002. Turk. Acta Pharm. Turc. 44 (3), 195. Ersoz, T., Saracoglu, I., Harput, U.S., Calis, I., Donmez, Ali A., 2002a. Turk. J. Chem. 26 (2), 171. Ersoz, T., Harput, U.S., Calis, I., Donmez, Ali A., 2002b. Turk. J. Chem. 26 (1), 1. Ersoz, T., Saracoglu, I., Kirmizibekmez, H., Yalcin, F.N., Harput, U.S., Donmez, Ali A., Calis, I., 2001a. Hacettepe Univ. Eczaci. Fak. Derg. 21 (1), 23. Ersoz, T., Schuhly, W., Popov, S., Handjieva, N., Sticher, O., Calis, I., 2001b. Nat. Prod. Lett. 15 (5), 345. Ersoz, T., Ivancheva, S., Akbay, P., Sticher, O., Calis, I., 2001c. Z. Naturforsch. C 56 (9/10), 695. Harput, U.S., Saracoglu, I., Calis, I., 1999. Hacettepe Univ. Eczaci. Fak. Derg. 19 (1), 1. Kabouche, Z., Benkiki, N., Seguin, E., Bruneau, C., 2003. Fitoterapia 74, 194. Kamel, M.S., Mohamed, K.M., Hassanean, H.A., Ohtani, K., Kasai, R., Yamasaki, K., 2000. Phytochemistry 55 (4), 353. Kyriakopoulou, I., Magiatis, P., Skaltsounis, A.-L., Aligiannis, N., Harvala, C., 2001. J. Nat. Prod. 64 (8), 1095. Mabry, T.J., Markham, K.R., Thomas, M.B., 1970. The Systematic Identification of Flavonoids. Springer, New York. Markham, K.R., 1982. Techniques of Flavonoid Identification. Academic Press, London. Quezel, P., Santa, S., 1963. Nouvelle flore de l’Alge´rie et des Re´gions De´sertiques et Me´ridionales, Tome II. Editions CNRS, Paris (in French). Saracoglu, I., Inoue, M., Calis, I., Ogihara, Y., 1995. Biol. Pharm. Bull. 18 (10), 1396. Takeda, Y., Kinugawa, M., Masuda, T., Honda, G., Otsuka, H., Sezik, E., Yesilada, E., 1999. Phytochemistry 51 (2), 323. Toma´s-Barbera´n, F.A., Gil, M.I., Ferreres, F., Toma´s-Lorente, F., 1992. Phytochemistry 31 (9), 3097. Toma´s, F., Nieto, J.L., Barbera´n, F.A.T., Ferreres, F., 1986. Phytochemistry 25, 1253. Yalcin, F.N., Ersoez, T., Akbay, P., Calis, I., Doenmez, Ali A., Sticher, O., 2003. Turk. J. Chem. 27 (3), 295.