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Two major flavonoids from Ballota nigra
Biochemical Systematics and Ecology 28 (2000) 1031}1033
Two major #avonoids from Ballota nigra Marie-Caroline Bertrand , Franc7 ois Tillequin, Franc7 ois Bailleul * Laboratoire de Pharmacognosie, Faculte& des Sciences Pharmaceutiques et Biologiques, Universite de Lille 2, BP 83, 59006 Lille Cedex, France Laboratoire de Pharmacognosie, Faculte& des Sciences Pharmaceutiques et Biologiques, URA au CNRS no. 1310, 4, Avenue de l'Observatoire, 75006 Paris, France Received 7 October 1999; accepted 20 December 1999
Abstract Two lactoylated #avonoids, luteolin-7-lactate and luteolin-7-glucosyl-lactate were isolated from Ballota nigra. They should be used for the chemical standardization of this drug of medicinal interest. 2000 Elsevier Science Ltd. All rights reserved. Keywords: Ballota nigra; Flavonoid lactates; Luteolin-7-lactate; Luteolin-7-glucosyl-lactate
1. Subject and source Ballota nigra L. (Lamiaceae) is a perennial herb which is commonly distributed in Western Europe where #owering aerial parts are used in medicine for treating cough and more especially for neurosedative activities (Wichtl and Anton, 1999). Ballota nigra was collected in 1996 in the vicinity of Angers (France) and identi"ed in comparison with an authentic sample cultivated in the University of Lille Botanical Garden (France). A voucher specimen is kept in the Department of Pharmacognosy of that University (No. B.n. 5).
2. Previous work Previous investigations of the aerial parts resulted in the isolation of the #avonoids apigenin-7-glucoside, vicenin-2 (Darbour et al., 1986) and tangeretin (Kisiel and * Corresponding author. Tel./fax: #33-3-20-96-40-39. E-mail address: [email protected] (F. Bailleul) 0305-1978/00/$ - see front matter 2000 Elsevier Science Ltd. All rights reserved. PII: S 0 3 0 5 - 1 9 7 8 ( 0 0 ) 0 0 0 1 5 - 6
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M.-C. Bertrand et al. / Biochemical Systematics and Ecology 28 (2000) 1031}1033
Piozzi, 1995) and the labdane diterpenoids ballotinone (Savona et al., 1976a), ballonigrine (Savona et al., 1976b), 7a-acetoxymarrubiin (Savona et al., 1977a), ballotenol (Savona et al., 1977b), preleosibirin (Bruno et al., 1986) and 13-hydroxyballonigrinolide (Seidel et al., 1996a). Recent studies of an alcoholic extract led to the isolation of seven phenylpropanoid glycosides: verbascoside, forsythoside B, arenarioside, ballotetroside, alyssonoside, lavandulifolioside and angoroside A and a non-glycosidic derivative: (#)-(E)-ca!eoyl-L-malic acid (Seidel et al., 1996b, 1997 and Didry et al., 1999). Pharmacological studies were carried out on the major phenylpropanoid derivatives isolated from Ballota nigra. These compounds could account for the neurosedative activity of the drug. In addition, they exhibit potent antioxidant activities which are of therapeutic interest (Daels-Rakotoarison et al., 2000; Seidel et al., 2000). 3. Present study A MeOH : H O 3 : 7 extract of the dried aerial parts of Ballota nigra (120 g) was submitted to repeated gel "ltration chromatographies (Sephadex LH-20 eluting with H O). Fractions containing 1 and 2 were further puri"ed separatively by CC on cellulose eluting with H O a!ording the known #avonoids luteolin-7-O-lactate 1 (90 mg) and luteolin-7-O-[2-O-b-D-glycopyranosyl-lactate] 2 (94 mg). Spectral data (UV, H and C NMR) of 1 and 2 are identical to those previously described (Nawwar et al., 1989). The spectra are available from the Lille laboratory. Chemical correlations (treatment with CH N , controlled acid and alkaline hydrolysis) were used to con"rm the linkages of the di!erent moieties which were not previously unambiguously determined as 1 and 2.
4. Chemotaxonomic signi5cance The isolation of 1 and 2 from Ballota nigra is of chemotaxonomic interest as lactoylated #avonoids are very rare plant constituents here reported for the "rst time in the genus Ballota. Up till now these two compounds were only described in one species of the related genus Marrubium, M. vulgare (Nawwar et al., 1989).
M.-C. Bertrand et al. / Biochemical Systematics and Ecology 28 (2000) 1031}1033
1033
It should be emphasized that 1 and 2 are the major #avonoids isolated from Ballota nigra, other #avonoids previously described being present only in very small amounts. Consequently, 1 and 2 should be used for the chemical standardization of the drug and its extracts of medicinal interest.
Acknowledgements Authors are grateful to Agence Franc7 aise de SeH curiteH Sanitaire des Produits de SanteH *UniteH de PharmacopeH e for "nancial support (Grant No. 179).
References Bruno, M., Savona, G., Pascual, C., Rodriguez, B., 1986. Phytochemisty 25, 538. Daels-Rakotoarison, D.A., Seidel, V., Gressier, B., Brunet, C., Tillequin, F., Luyckx, M., Bailleul, F., Cazin, M., Cazin, J.C., 2000. Arzneim. Forsch. Drug Res. 50, I, 16. Darbour, N., Baltassat, F., Raynaud, J., 1986. Pharmazie 41, 605. Didry, N., Seidel, V., Dubreuil, L., Tillequin, F., Bailleul, F., 1999. J. Ethnopharmacol. 67 (2), 197. Kisiel, W., Piozzi, F., 1995. Pol. J. Chem. 69, 476. Nawwar, M.A.M., El-Moussalamy, A.M.D., Barakat, H.H., Buddrus, J., Linscheid, M., 1989. Phytochemistry 28, 3201. Savona, G., Piozzi, F., Hanson, J.R., Siverns, M., 1976a. J. Chem. Soc. Perkin Trans. 1, 1607. Savona, G., Piozzi, F., Hanson, J.R., Siverns, M., 1976b. Chim. Ind., Milan 58, 378. Savona, G., Piozzi, F., Hanson, J.R., Siverns, M., 1977a. J. Chem. Soc. Perkin Trans. 1, 322. Savona, G., Piozzi, F., Hanson, J.R., Siverns, M., 1977b. J. Chem. Soc. Perkin Trans. 1, 497. Seidel, V., Bailleul, F., Libot, F., Tillequin, F., 1997. Phytochemistry 44, 691. Seidel, V., Bailleul, F., Tillequin, F., 1996a. J. Pharm. Belg. 51, 72. Seidel, V., Bailleul, F., Tillequin, F., 1996b. Planta Med. 62, 186. Seidel, V., Verholle, M., Malard, Y., Tillequin, F., Fruchart, J.C., Duriez, P., Bailleul, F., Teissier, E., 2000. Phytoth. Res. 14, 93. Wichtl, M., Anton, R., 1999. Plantes theH rapeutiques. Tec & Doc, Paris.
Two major #avonoids from Ballota nigra Marie-Caroline Bertrand , Franc7 ois Tillequin, Franc7 ois Bailleul * Laboratoire de Pharmacognosie, Faculte& des Sciences Pharmaceutiques et Biologiques, Universite de Lille 2, BP 83, 59006 Lille Cedex, France Laboratoire de Pharmacognosie, Faculte& des Sciences Pharmaceutiques et Biologiques, URA au CNRS no. 1310, 4, Avenue de l'Observatoire, 75006 Paris, France Received 7 October 1999; accepted 20 December 1999
Abstract Two lactoylated #avonoids, luteolin-7-lactate and luteolin-7-glucosyl-lactate were isolated from Ballota nigra. They should be used for the chemical standardization of this drug of medicinal interest. 2000 Elsevier Science Ltd. All rights reserved. Keywords: Ballota nigra; Flavonoid lactates; Luteolin-7-lactate; Luteolin-7-glucosyl-lactate
1. Subject and source Ballota nigra L. (Lamiaceae) is a perennial herb which is commonly distributed in Western Europe where #owering aerial parts are used in medicine for treating cough and more especially for neurosedative activities (Wichtl and Anton, 1999). Ballota nigra was collected in 1996 in the vicinity of Angers (France) and identi"ed in comparison with an authentic sample cultivated in the University of Lille Botanical Garden (France). A voucher specimen is kept in the Department of Pharmacognosy of that University (No. B.n. 5).
2. Previous work Previous investigations of the aerial parts resulted in the isolation of the #avonoids apigenin-7-glucoside, vicenin-2 (Darbour et al., 1986) and tangeretin (Kisiel and * Corresponding author. Tel./fax: #33-3-20-96-40-39. E-mail address: [email protected] (F. Bailleul) 0305-1978/00/$ - see front matter 2000 Elsevier Science Ltd. All rights reserved. PII: S 0 3 0 5 - 1 9 7 8 ( 0 0 ) 0 0 0 1 5 - 6
1032
M.-C. Bertrand et al. / Biochemical Systematics and Ecology 28 (2000) 1031}1033
Piozzi, 1995) and the labdane diterpenoids ballotinone (Savona et al., 1976a), ballonigrine (Savona et al., 1976b), 7a-acetoxymarrubiin (Savona et al., 1977a), ballotenol (Savona et al., 1977b), preleosibirin (Bruno et al., 1986) and 13-hydroxyballonigrinolide (Seidel et al., 1996a). Recent studies of an alcoholic extract led to the isolation of seven phenylpropanoid glycosides: verbascoside, forsythoside B, arenarioside, ballotetroside, alyssonoside, lavandulifolioside and angoroside A and a non-glycosidic derivative: (#)-(E)-ca!eoyl-L-malic acid (Seidel et al., 1996b, 1997 and Didry et al., 1999). Pharmacological studies were carried out on the major phenylpropanoid derivatives isolated from Ballota nigra. These compounds could account for the neurosedative activity of the drug. In addition, they exhibit potent antioxidant activities which are of therapeutic interest (Daels-Rakotoarison et al., 2000; Seidel et al., 2000). 3. Present study A MeOH : H O 3 : 7 extract of the dried aerial parts of Ballota nigra (120 g) was submitted to repeated gel "ltration chromatographies (Sephadex LH-20 eluting with H O). Fractions containing 1 and 2 were further puri"ed separatively by CC on cellulose eluting with H O a!ording the known #avonoids luteolin-7-O-lactate 1 (90 mg) and luteolin-7-O-[2-O-b-D-glycopyranosyl-lactate] 2 (94 mg). Spectral data (UV, H and C NMR) of 1 and 2 are identical to those previously described (Nawwar et al., 1989). The spectra are available from the Lille laboratory. Chemical correlations (treatment with CH N , controlled acid and alkaline hydrolysis) were used to con"rm the linkages of the di!erent moieties which were not previously unambiguously determined as 1 and 2.
4. Chemotaxonomic signi5cance The isolation of 1 and 2 from Ballota nigra is of chemotaxonomic interest as lactoylated #avonoids are very rare plant constituents here reported for the "rst time in the genus Ballota. Up till now these two compounds were only described in one species of the related genus Marrubium, M. vulgare (Nawwar et al., 1989).
M.-C. Bertrand et al. / Biochemical Systematics and Ecology 28 (2000) 1031}1033
1033
It should be emphasized that 1 and 2 are the major #avonoids isolated from Ballota nigra, other #avonoids previously described being present only in very small amounts. Consequently, 1 and 2 should be used for the chemical standardization of the drug and its extracts of medicinal interest.
Acknowledgements Authors are grateful to Agence Franc7 aise de SeH curiteH Sanitaire des Produits de SanteH *UniteH de PharmacopeH e for "nancial support (Grant No. 179).
References Bruno, M., Savona, G., Pascual, C., Rodriguez, B., 1986. Phytochemisty 25, 538. Daels-Rakotoarison, D.A., Seidel, V., Gressier, B., Brunet, C., Tillequin, F., Luyckx, M., Bailleul, F., Cazin, M., Cazin, J.C., 2000. Arzneim. Forsch. Drug Res. 50, I, 16. Darbour, N., Baltassat, F., Raynaud, J., 1986. Pharmazie 41, 605. Didry, N., Seidel, V., Dubreuil, L., Tillequin, F., Bailleul, F., 1999. J. Ethnopharmacol. 67 (2), 197. Kisiel, W., Piozzi, F., 1995. Pol. J. Chem. 69, 476. Nawwar, M.A.M., El-Moussalamy, A.M.D., Barakat, H.H., Buddrus, J., Linscheid, M., 1989. Phytochemistry 28, 3201. Savona, G., Piozzi, F., Hanson, J.R., Siverns, M., 1976a. J. Chem. Soc. Perkin Trans. 1, 1607. Savona, G., Piozzi, F., Hanson, J.R., Siverns, M., 1976b. Chim. Ind., Milan 58, 378. Savona, G., Piozzi, F., Hanson, J.R., Siverns, M., 1977a. J. Chem. Soc. Perkin Trans. 1, 322. Savona, G., Piozzi, F., Hanson, J.R., Siverns, M., 1977b. J. Chem. Soc. Perkin Trans. 1, 497. Seidel, V., Bailleul, F., Libot, F., Tillequin, F., 1997. Phytochemistry 44, 691. Seidel, V., Bailleul, F., Tillequin, F., 1996a. J. Pharm. Belg. 51, 72. Seidel, V., Bailleul, F., Tillequin, F., 1996b. Planta Med. 62, 186. Seidel, V., Verholle, M., Malard, Y., Tillequin, F., Fruchart, J.C., Duriez, P., Bailleul, F., Teissier, E., 2000. Phytoth. Res. 14, 93. Wichtl, M., Anton, R., 1999. Plantes theH rapeutiques. Tec & Doc, Paris.