IDENTIFICATION OF ARYLTETRALIN LIGNANS FROM PODOPHYLLUM HEXANDRUM USING HYPHENATED TECHNIQUES
Abstract
In the present study, with the appliance of hyphenated techniques involving high performance liquid chromatography with diode array detection directly coupled with 1H nuclear magnetic resonance spectroscopy (LC-NMR) and electrospray ionization mass spectrometry (LC-ESI-MS), four known aryltetrahydronephthalene lignans (podophyllotoxin 4-O-glucopyranoside, 4’-demethylpodophyllotoxin, podophyllotxin and dehydropodophyllotoxin) have been well characterized from methanol extract of rhizomes of Podophyllum hexandrum Royle without involving the time consuming steps of isolation and purification of individual constituents of the extract. Also, a simple, sensitive and reproducible LC-MS method has been developed for the quantitative analysis of podophyllotoxin in crude methanolic extract from different parts of Podophyllum hexandrum Royle. The present work adds up to the existing significance of hyphenated techniques combining chromatographic technologies with spectroscopic techniques for both qualitative and quantitative analysis of natural product extracts or fractions without any need of reference standards for the markers.
Keywords:
Podophyllum hexandrum, LC-MS, LC-NMR, podophyllaceae, phytochemical study, aryltetrahydronephthalene lignans, podophyllotoxinDOI
https://doi.org/10.25004/IJPSDR.2015.070115References
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2. Gupta R, Sethi KL, Conservation of medicinal plant resources in Himalayan region. Jain SK, Mehra KL (Eds.), Conservation of tropical plant resources, BSI, Howrah, India, 1983; 101-107.
3. Nayar MP, Sastry APK. Red Data Book of Indian Plants. Botanical Survey of Kolkata, India, 1990.
4. Choudhary DK, Kaul BL, Khan S. Cultivation and conservation of Podophyllum hexandrum- An overview. J. Med. Aro. Plant Sci. 1998; 20: 1071-1073.
5. a) Nayar SL, Chopra IC. Distribution of British pharmacopoeial drug plants and their substitutes growing in India. Pharmaceutical and Drugs Research Committee, Council of Scientific & Industrial Research, New Delhi, India, 1951: 56; b) Kumar S, Singh J, Shah NC, Ranjan V. Indian Medicinal Plants Facing Genetic Erosion. Central Institute of Medicinal & Aromatic Plants, CSIR, Lucknow, India, 1997: 205.
6. Iqbal M, Beigh SY, Nawchoo IA. Variability in morphology and active constituents of P. hexandrum- a Himalayan herb known for its anti-cancer activity. J. Tropical Medicinal Plants 2004; 5: 33-36.
7. Singh J, Shah NC. Podophyllum: a review. Curr. Res. Med. Arom. Plants 1994; 116: 53-83.
8. Kamil MW, Dewick PM. Biosynthetic relationship of aryltetralin lactone lignans to dibenzylbutyrolactone lignans. Phytochemistry 1986; 25: 2093-2102.
9. Jackson DE, Dewick PM. Aryltetralin lignans from Podophyllum hexandrum and Podophyllum peltatum. Phytochemistry 1984; 23(5): 1147-1152.
10. Lee CTL, Lin VCK, Zhang SX, Zhu XK, Vliet DV, Hu H, Beers SA, Wang ZQ, Cosentino LM, Morris-Natschke SL, Lee KH. Anti-AIDS agents. Anti-HIV activity of modified podophyllotoxin derivatives. Bioorg. Med. Chem. Lett. 1997; 7: 2897-2902.
11. Liu KCSC, Lee SS, Lin MT, Chang CW, Liu CL, Lin JY, Hsu FL, Ren S, Lien EJ. Lignans and tannins as inhibitors of viral reverse transcriptase and human DNA polymerase-A: QSAR analysis and molecular modeling. Med. Chem. Res. 1997; 7: 168-179.
12. Hara H, Fujihashi T, Sakata T, Kaji A, Kaji H. Tetrahydronaphthalene lignan compounds as potent anti-HIV type 1 agents. AIDS Res. Hum. Retroviruses 1997; 13: 695-705.
13. Gordaliza M, Castro MA, Miguel del Corral JM, Lopez-Vazquez ML, San Feliciano A, Faircloth GT. In vivo immunosuppressive activity of some cyclolignans. Bioorg. Med. Chem. Lett. 1997; 7: 2781-2786.
14. Ghisalberti EL. Cardiovascular activity of naturally occurring lignans. Phytomedicine 1997; 4: 151-166.
15. Costa MCA, Takahata Y. Conformational analysis of synthetic neolignans active against leishmaniasis, using the molecular mechanics method (MM2). J. Comput. Chem. 1997; 18: 712-721.
16. a) Iwasaki T, Kondo K, Nishitani T, Kuroda T, Hirakoso K, Ohtani A, Takashima K. Arylnaphthalene lignans as novel series of hypolipidemic agents raising high-density lipoprotein level. Chem. Pharm. Bull. 1995; 43: 1701-1705; b) Kuroda T, Kondo K, Iwasaki T, Ohtani A, Takashima K. Synthesis and hypolipidemic activity of diesters of arylnaphthalene lignan and their heteroaromatic analogs. Chem. Pharm. Bull. 1997; 45: 678-684.
17. Patel D, Vaghasiya J, Pancholi SS, Paul A. Therapeutic Potential of Secoisolariciresinol Diglucoside: A Plant Lignan. International Journal of Pharmaceutical Sciences and Drug Research 2012; 4(1): 15-18.
18. Delorme D, Ducharme Y, Brideau C, Chan CC, Chauret N, Desmarais S, Dube D, Falgueyret JP, Fortin R, Guay J, Hamel P, Jones TR, Lepine C, McAuliffe M, McFarlane CS, Nicoll-Griffith DA, Riendeau D, Yergey JA, Girard Y. Dioxabicyclooctanyl naphthalenenitriles as nonredox 5-lipoxygenase inhibitors: structure-activity relationship study directed toward the improvement of metabolic stability. J. Med. Chem. 1996; 39: 3951-3970.
19. Zacchino S, Rodriguez G, Pezzenati G, Orellana G. In vitro evaluation of antifungal properties of 8.O.4’-neolignans. J. Nat. Prod. 1997; 60: 659-662.
20. Rantapaa-Dahlqvist S, Landberg G, Roos G, Norberg B. Cell cycle effects of the anti-rheumatic agent CPH82. Br. J. Rheumatol. 1994; 33: 327-331.
21. Lerndal T, Svensson B. A clinical study of CPH 82 vs. methotrexate in early rheumatoid arthritis. Rheumatology (Oxford) 2000; 39: 316-320.
22. Leander K, Rosen B. Medicinal uses for podophyllotoxin. US patent 1988; 4: 788, 216.
23. Bedows E, Hatfield G. An investigation of the antiviral activity of podophyllum peltatum. J. Nat. Prod. 1982; 45: 725-729.
24. Bala M, Goel HC. Radioprotective effect of podophyllotoxin in Saccharomyces cerevisiae. Journal of Environmental Pathology Toxicology and Oncology 2004; 23: 139-144
25. Issell BF, Muggia FM, Carter SK. Etoposide (VP-16)- Current Status and New Developments. Academic Press, Orlando, USA, 1984.
26. Stahelin HF, Wartburg AV. The chemical and biological route form podophyllotoxin glucoside to etoposide: Ninth Cain Memorail Award Lecture. Cancer Res 1991; 51: 5-15.
27. Canwl C, Moraes RM, Dayan FE, Ferreira D. Molecules of interest Podophyllotoxin. Phytochemistry 2000; 54: 15-20.
28. a) Cairnes DA, Kingston DGI, Rao MM. High Performance Liquid Chromatography of Podophyllotoxins and Related Lignans. J. Nat. Prod. 1981; 44 (1): 34-37; b) Wong SK, Tusi SK, Kwan SY, Su XL, Lin RC. Identification and characterization of Podophyllum emodi by API-LC/MS/MS. J. Mass Spectrom. 2000; 35:1246-1251.
29. Puri SC, Handa, G, Bhat BA, Dhar KL, Spiteller M, Qazi GN. Characterization of Two Epimers, 4α and 4β, of a Novel Podophyllotoxin-4-O-(D)-6-Acetylglucopyranoside from Podophyllum hexandrum by LC-ESI-MS-MS. Journal of Chromatographic Science 2006; 44(5): 239-243.
30. Lin MC, Lin JH, Chen SK, Cheng YW, Cheng HW. Simultaneous Determination of Podophyllotoxin, Quercetin and Kaempferol in Podophyllin by Liquid Chromatography-Tandem Mass Spectrometry. Journal of Food and Drug Analysis 2008; 16(6): 29-40.
31. a) Bastos JK, Burandt Jr CL, Nanayakara NPD, Bryanat L, McChesney JD. Quantitation of aryltetralin lignans in plant parts and among different populations of Podophyllum peltatum by reversed-phase high-performance liquid chromatography. J. Nat. Prod 1996; 59: 406-408; b) Sharma V. Part Based HPLC-PDA Quantification of Podophyllotoxin in Populations of Podophyllum hexandrum Royle “Indian Mayapple” from Higher Altitude Himalayas. Journal of Medicinal Plants Studies 2013; 1(3): 176-183.
32. Wilson ID, Brinkman UA. Hyphenation and hypernation: the practice and prospects of multiple hyphenation. J Chromatogr A 2003; 1000: 325-356.
33. Wolfender JL, Ndjoko K, Hostettmann K. LC/NMR in natural products chemistry. Curr. Org. Chem. 1998; 2: 575-596.
34. Wolfender JL, Rodriguez S, Hostettmann K. Liquid chromatography coupled to mass spectrometry and nuclear magnetic resonance spectroscopy for the screening of plant constituents. J Chromatogr. A 1998; 794: 299-316.
2. Gupta R, Sethi KL, Conservation of medicinal plant resources in Himalayan region. Jain SK, Mehra KL (Eds.), Conservation of tropical plant resources, BSI, Howrah, India, 1983; 101-107.
3. Nayar MP, Sastry APK. Red Data Book of Indian Plants. Botanical Survey of Kolkata, India, 1990.
4. Choudhary DK, Kaul BL, Khan S. Cultivation and conservation of Podophyllum hexandrum- An overview. J. Med. Aro. Plant Sci. 1998; 20: 1071-1073.
5. a) Nayar SL, Chopra IC. Distribution of British pharmacopoeial drug plants and their substitutes growing in India. Pharmaceutical and Drugs Research Committee, Council of Scientific & Industrial Research, New Delhi, India, 1951: 56; b) Kumar S, Singh J, Shah NC, Ranjan V. Indian Medicinal Plants Facing Genetic Erosion. Central Institute of Medicinal & Aromatic Plants, CSIR, Lucknow, India, 1997: 205.
6. Iqbal M, Beigh SY, Nawchoo IA. Variability in morphology and active constituents of P. hexandrum- a Himalayan herb known for its anti-cancer activity. J. Tropical Medicinal Plants 2004; 5: 33-36.
7. Singh J, Shah NC. Podophyllum: a review. Curr. Res. Med. Arom. Plants 1994; 116: 53-83.
8. Kamil MW, Dewick PM. Biosynthetic relationship of aryltetralin lactone lignans to dibenzylbutyrolactone lignans. Phytochemistry 1986; 25: 2093-2102.
9. Jackson DE, Dewick PM. Aryltetralin lignans from Podophyllum hexandrum and Podophyllum peltatum. Phytochemistry 1984; 23(5): 1147-1152.
10. Lee CTL, Lin VCK, Zhang SX, Zhu XK, Vliet DV, Hu H, Beers SA, Wang ZQ, Cosentino LM, Morris-Natschke SL, Lee KH. Anti-AIDS agents. Anti-HIV activity of modified podophyllotoxin derivatives. Bioorg. Med. Chem. Lett. 1997; 7: 2897-2902.
11. Liu KCSC, Lee SS, Lin MT, Chang CW, Liu CL, Lin JY, Hsu FL, Ren S, Lien EJ. Lignans and tannins as inhibitors of viral reverse transcriptase and human DNA polymerase-A: QSAR analysis and molecular modeling. Med. Chem. Res. 1997; 7: 168-179.
12. Hara H, Fujihashi T, Sakata T, Kaji A, Kaji H. Tetrahydronaphthalene lignan compounds as potent anti-HIV type 1 agents. AIDS Res. Hum. Retroviruses 1997; 13: 695-705.
13. Gordaliza M, Castro MA, Miguel del Corral JM, Lopez-Vazquez ML, San Feliciano A, Faircloth GT. In vivo immunosuppressive activity of some cyclolignans. Bioorg. Med. Chem. Lett. 1997; 7: 2781-2786.
14. Ghisalberti EL. Cardiovascular activity of naturally occurring lignans. Phytomedicine 1997; 4: 151-166.
15. Costa MCA, Takahata Y. Conformational analysis of synthetic neolignans active against leishmaniasis, using the molecular mechanics method (MM2). J. Comput. Chem. 1997; 18: 712-721.
16. a) Iwasaki T, Kondo K, Nishitani T, Kuroda T, Hirakoso K, Ohtani A, Takashima K. Arylnaphthalene lignans as novel series of hypolipidemic agents raising high-density lipoprotein level. Chem. Pharm. Bull. 1995; 43: 1701-1705; b) Kuroda T, Kondo K, Iwasaki T, Ohtani A, Takashima K. Synthesis and hypolipidemic activity of diesters of arylnaphthalene lignan and their heteroaromatic analogs. Chem. Pharm. Bull. 1997; 45: 678-684.
17. Patel D, Vaghasiya J, Pancholi SS, Paul A. Therapeutic Potential of Secoisolariciresinol Diglucoside: A Plant Lignan. International Journal of Pharmaceutical Sciences and Drug Research 2012; 4(1): 15-18.
18. Delorme D, Ducharme Y, Brideau C, Chan CC, Chauret N, Desmarais S, Dube D, Falgueyret JP, Fortin R, Guay J, Hamel P, Jones TR, Lepine C, McAuliffe M, McFarlane CS, Nicoll-Griffith DA, Riendeau D, Yergey JA, Girard Y. Dioxabicyclooctanyl naphthalenenitriles as nonredox 5-lipoxygenase inhibitors: structure-activity relationship study directed toward the improvement of metabolic stability. J. Med. Chem. 1996; 39: 3951-3970.
19. Zacchino S, Rodriguez G, Pezzenati G, Orellana G. In vitro evaluation of antifungal properties of 8.O.4’-neolignans. J. Nat. Prod. 1997; 60: 659-662.
20. Rantapaa-Dahlqvist S, Landberg G, Roos G, Norberg B. Cell cycle effects of the anti-rheumatic agent CPH82. Br. J. Rheumatol. 1994; 33: 327-331.
21. Lerndal T, Svensson B. A clinical study of CPH 82 vs. methotrexate in early rheumatoid arthritis. Rheumatology (Oxford) 2000; 39: 316-320.
22. Leander K, Rosen B. Medicinal uses for podophyllotoxin. US patent 1988; 4: 788, 216.
23. Bedows E, Hatfield G. An investigation of the antiviral activity of podophyllum peltatum. J. Nat. Prod. 1982; 45: 725-729.
24. Bala M, Goel HC. Radioprotective effect of podophyllotoxin in Saccharomyces cerevisiae. Journal of Environmental Pathology Toxicology and Oncology 2004; 23: 139-144
25. Issell BF, Muggia FM, Carter SK. Etoposide (VP-16)- Current Status and New Developments. Academic Press, Orlando, USA, 1984.
26. Stahelin HF, Wartburg AV. The chemical and biological route form podophyllotoxin glucoside to etoposide: Ninth Cain Memorail Award Lecture. Cancer Res 1991; 51: 5-15.
27. Canwl C, Moraes RM, Dayan FE, Ferreira D. Molecules of interest Podophyllotoxin. Phytochemistry 2000; 54: 15-20.
28. a) Cairnes DA, Kingston DGI, Rao MM. High Performance Liquid Chromatography of Podophyllotoxins and Related Lignans. J. Nat. Prod. 1981; 44 (1): 34-37; b) Wong SK, Tusi SK, Kwan SY, Su XL, Lin RC. Identification and characterization of Podophyllum emodi by API-LC/MS/MS. J. Mass Spectrom. 2000; 35:1246-1251.
29. Puri SC, Handa, G, Bhat BA, Dhar KL, Spiteller M, Qazi GN. Characterization of Two Epimers, 4α and 4β, of a Novel Podophyllotoxin-4-O-(D)-6-Acetylglucopyranoside from Podophyllum hexandrum by LC-ESI-MS-MS. Journal of Chromatographic Science 2006; 44(5): 239-243.
30. Lin MC, Lin JH, Chen SK, Cheng YW, Cheng HW. Simultaneous Determination of Podophyllotoxin, Quercetin and Kaempferol in Podophyllin by Liquid Chromatography-Tandem Mass Spectrometry. Journal of Food and Drug Analysis 2008; 16(6): 29-40.
31. a) Bastos JK, Burandt Jr CL, Nanayakara NPD, Bryanat L, McChesney JD. Quantitation of aryltetralin lignans in plant parts and among different populations of Podophyllum peltatum by reversed-phase high-performance liquid chromatography. J. Nat. Prod 1996; 59: 406-408; b) Sharma V. Part Based HPLC-PDA Quantification of Podophyllotoxin in Populations of Podophyllum hexandrum Royle “Indian Mayapple” from Higher Altitude Himalayas. Journal of Medicinal Plants Studies 2013; 1(3): 176-183.
32. Wilson ID, Brinkman UA. Hyphenation and hypernation: the practice and prospects of multiple hyphenation. J Chromatogr A 2003; 1000: 325-356.
33. Wolfender JL, Ndjoko K, Hostettmann K. LC/NMR in natural products chemistry. Curr. Org. Chem. 1998; 2: 575-596.
34. Wolfender JL, Rodriguez S, Hostettmann K. Liquid chromatography coupled to mass spectrometry and nuclear magnetic resonance spectroscopy for the screening of plant constituents. J Chromatogr. A 1998; 794: 299-316.
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01-01-2015
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“IDENTIFICATION OF ARYLTETRALIN LIGNANS FROM PODOPHYLLUM HEXANDRUM USING HYPHENATED TECHNIQUES”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 7, no. 1, Jan. 2015, pp. 83-88, https://doi.org/10.25004/IJPSDR.2015.070115.
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“IDENTIFICATION OF ARYLTETRALIN LIGNANS FROM PODOPHYLLUM HEXANDRUM USING HYPHENATED TECHNIQUES”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 7, no. 1, Jan. 2015, pp. 83-88, https://doi.org/10.25004/IJPSDR.2015.070115.
