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Cytotoxic activity of Ozoroa insignis from Zimbabwe
Fitoterapia 74 (2003) 732–735
Short report
Cytotoxic activity of Ozoroa insignis from Zimbabwe Angela I. Reaa, Jennifer M. Schmidta, William N. Setzera, Samson Sibandab, Catherine Taylorc, Ephraim T. Gwebuc,* a
Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA Department of Applied Chemistry, National University of Science and Technology Bulawayo, Zimbabwe c Department of Chemistry, Oakwood College Huntsville, AL 35896, USA
b
Received 6 March 2003; accepted 6 August 2003
Abstract The crude methanol bark extract of the Zimbabwean medicinal plant, Ozoroa insignis, showed in-vitro cytotoxic activity against Hep-G2 (human hepatocellular carcinoma), MDAMB-231 (human mammary adenocarcinoma), and 5637 (human primary bladder carcinoma). Bioactivity-directed chromatographic separation led to isolation of anacardic acid and ginkgoic acid as the cytotoxic components. 䊚 2003 Elsevier Science B.V. All rights reserved. Keywords: Ozoroa insignis; Cytotoxicity; Anacardic acid; Ginkgoic acid
Plant. Ozoroa insignis Delile (Anacardiaceae), known as isafice (Ndebele), chibvukati (Shona) or chaficha (Tonga), bark collected from Christon Bank Nature Reserve near Mazowe Dam almost 30 km north of Harare, and identified at the National Herbarium and Botanic Garden of Zimbabwe, voucher specimen No. 970704. *Corresponding author. Tel.: q1-256-726-7502; fax: q1-256-726-8369. E-mail address: [email protected] (E.T. Gwebu). 0367-326X/03/$ - see front matter 䊚 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/j.fitote.2003.08.007
A.I. Rea et al. / Fitoterapia 74 (2003) 732–735
733
Fig. 1. Cytotoxic compounds of Ozoroa insignis bark.
Uses in traditional medicine. Bark, leaves, and roots of this plant are used medicinally in Zimbabwe. An infusion of the root or bark of this plant is commonly used to treat diarrhea and venereal diseases. This plant is also used to treat tapeworm and hookworm w1x as well as urinary schistosomiasis w2,3x. Previously isolated constituents. 6-Pentadecylsalicylic acid (anacardic acid, 1 (Fig. 1)) has been isolated by bioactivity-directed (Artemia salina lethality) fractionation from the dichloromethane extract of twigs of O. insignis w4x. New isolated constituents. From the methanol bark extract 6-(8-Z-pentadecenyl)salicylic acid (ginkgoic acid, 2 (Fig. 1)), (33 mg from 18 g of methanol extract) isolated by bioactivity-directed (cytotoxicity) chromatographic separation. Tested material. The crude plant extract, chromatographic fractions, anacardic acid (1) and ginkgoic acid (2). Studied activity. In-vitro cytotoxicity against Hep G2 (human hepatocellular carcinoma), MDA-MB-231 (human mammary adenocarcinoma), Hs 578T (human mammary ductal carcinoma), MCF7 (human mammary adenocarcinoma), SK-MEL28 (human melanoma), and 5637 (human primary bladder carcinoma) w5x. Results. Bioactivity-directed separation led to the isolation of anacardic acid (1) and ginkgoic acid (2) as the cytotoxic components. Structures were determined by
734
Material
Cytotoxicity Hep-G2
O. insignis bark extract Anacardic acid (1) Ginkgoic acid (2) Paclitaxel (Taxol䉸) a
86.96 (4.83) 229 (2) 385 (71) 58.7 (24.0)
MDA-MB-231 92.30 (3.58) 88.6 (2.3) 289 (54) 20.1 (7.7)
Hs 578T 32.64 (3.30) 89.3 (5.2) 88.9 (8.7) –
MCF7 11.0 (5.8) 89.5 (1.6) )300 –
SK-MEL-28 6.55 (2.49) 164 (11) 199 (11) –
5637 91.56 (2.21) 90.8 (3.2) 131.3 (1.0) –
Cytotoxicity of crude extracts (average of four replicates) are expressed as% kill at 250 mgyml except for 5637 cells, which were screened at 125 mgy ml. Cytotoxicity of 1 and 2 are IC50 values (mM). Standard deviations are shown in parentheses.
A.I. Rea et al. / Fitoterapia 74 (2003) 732–735
Table 1 Cytotoxic activitya of O. insignis bark extract, anacardic acid, and ginkoic acid
A.I. Rea et al. / Fitoterapia 74 (2003) 732–735
735
comparison of 1H and 13C NMR with those reported in the literature w6,7x. Cytotoxic activities are summarized in Table 1. Conclusions. Anacardic acid (1) and ginkgoic acid (2) are responsible for the cytotoxic activity of O. insignis bark extract, and this activity complements the biological activity observed in anacardic acids w4,8–14x. Acknowledgments Financial support: National Institutes of Health, Grant No. R15 GM57646-01A, (to ETG); the Research Board of the University of Zimbabwe, Grant No. 3YYH10y 3511 (to SS); and Research Genetics, Inc (to WNS). Traditional medical practitioners: Mr Nyoni of Mbizingwe under Chief Francis Mthonzima Gwebu of Umzingwane District and Mrs Ndule Sibanda of Nkayi District under Chief Madliwa Khumalo. Botanical identification: the late Mr Stephen Mavi (National Herbarium and Botanic Garden). Collection site: National Herbarium and Botanic Garden Nature Reserve. References w1x Gelfand M, Mavi S, Drummond RB, Ndemera B. The traditional medical practitioner in Zimbabwe. Gweru, Zimbabwe: Mambo Press, 1985. w2x Ndamba J, Nyazema N, Makaza N, Anderson C, Kaondera KC. J Ethnopharmacol 1994;42:125. w3x Molgaard P, Nielsen SB, Rasmussen DE, Drummond RB, Makaza N, Andreassen J. J Ethnopharmacol 2001;74:257. w4x He W, Van Puyvelde L, Bosselaers J, De Kimpe N, Van der Flaas M, Roymans A, et al. Pharm Biol 2002;40:74. w5x Setzer MC, Setzer WN, Jackes BR, Gentry GA, Moriarity DM. Pharm Biol 2001;39:67. w6x Gonzalez MJTG, DeOliviera CJC, Fernandes JO, Kijjoa A, Herz W. Phytochemistry 1996;43:1333. w7x Furstner ¨ A, Seidel G. J Org Chem 1997;62:2332. w8x Kubo I, Ochi M, Vieira PC, Komatsu S. J Agric Food Chem 1993;41:1012. w9x Muroi H, Kubo I. J Appl Bacteriol 1996;80:387. w10x Kubo J, Lee JR, Kubo I. J Agric Food Chem 1999;47:533. w11x Grazzini R, Hesk D, Heininger E, Hildenbrandt G, Reddy CC, Cox-Foster D, et al. Biochem Biophys Res Commun 1991;176:775. w12x Kubo I, Kinst-Hori I, Yokokawa Y. J Nat Prod 1994;57:545. w13x Shobha SV, Ramadoss CS, Ravindranath B. J Nat Prod 1994;57:1755. w14x Toyomizu M, Okamoto K, Ishibashi T, Chen Z, Nakatsu T. Life Sci 2000;66:229.
Short report
Cytotoxic activity of Ozoroa insignis from Zimbabwe Angela I. Reaa, Jennifer M. Schmidta, William N. Setzera, Samson Sibandab, Catherine Taylorc, Ephraim T. Gwebuc,* a
Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA Department of Applied Chemistry, National University of Science and Technology Bulawayo, Zimbabwe c Department of Chemistry, Oakwood College Huntsville, AL 35896, USA
b
Received 6 March 2003; accepted 6 August 2003
Abstract The crude methanol bark extract of the Zimbabwean medicinal plant, Ozoroa insignis, showed in-vitro cytotoxic activity against Hep-G2 (human hepatocellular carcinoma), MDAMB-231 (human mammary adenocarcinoma), and 5637 (human primary bladder carcinoma). Bioactivity-directed chromatographic separation led to isolation of anacardic acid and ginkgoic acid as the cytotoxic components. 䊚 2003 Elsevier Science B.V. All rights reserved. Keywords: Ozoroa insignis; Cytotoxicity; Anacardic acid; Ginkgoic acid
Plant. Ozoroa insignis Delile (Anacardiaceae), known as isafice (Ndebele), chibvukati (Shona) or chaficha (Tonga), bark collected from Christon Bank Nature Reserve near Mazowe Dam almost 30 km north of Harare, and identified at the National Herbarium and Botanic Garden of Zimbabwe, voucher specimen No. 970704. *Corresponding author. Tel.: q1-256-726-7502; fax: q1-256-726-8369. E-mail address: [email protected] (E.T. Gwebu). 0367-326X/03/$ - see front matter 䊚 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/j.fitote.2003.08.007
A.I. Rea et al. / Fitoterapia 74 (2003) 732–735
733
Fig. 1. Cytotoxic compounds of Ozoroa insignis bark.
Uses in traditional medicine. Bark, leaves, and roots of this plant are used medicinally in Zimbabwe. An infusion of the root or bark of this plant is commonly used to treat diarrhea and venereal diseases. This plant is also used to treat tapeworm and hookworm w1x as well as urinary schistosomiasis w2,3x. Previously isolated constituents. 6-Pentadecylsalicylic acid (anacardic acid, 1 (Fig. 1)) has been isolated by bioactivity-directed (Artemia salina lethality) fractionation from the dichloromethane extract of twigs of O. insignis w4x. New isolated constituents. From the methanol bark extract 6-(8-Z-pentadecenyl)salicylic acid (ginkgoic acid, 2 (Fig. 1)), (33 mg from 18 g of methanol extract) isolated by bioactivity-directed (cytotoxicity) chromatographic separation. Tested material. The crude plant extract, chromatographic fractions, anacardic acid (1) and ginkgoic acid (2). Studied activity. In-vitro cytotoxicity against Hep G2 (human hepatocellular carcinoma), MDA-MB-231 (human mammary adenocarcinoma), Hs 578T (human mammary ductal carcinoma), MCF7 (human mammary adenocarcinoma), SK-MEL28 (human melanoma), and 5637 (human primary bladder carcinoma) w5x. Results. Bioactivity-directed separation led to the isolation of anacardic acid (1) and ginkgoic acid (2) as the cytotoxic components. Structures were determined by
734
Material
Cytotoxicity Hep-G2
O. insignis bark extract Anacardic acid (1) Ginkgoic acid (2) Paclitaxel (Taxol䉸) a
86.96 (4.83) 229 (2) 385 (71) 58.7 (24.0)
MDA-MB-231 92.30 (3.58) 88.6 (2.3) 289 (54) 20.1 (7.7)
Hs 578T 32.64 (3.30) 89.3 (5.2) 88.9 (8.7) –
MCF7 11.0 (5.8) 89.5 (1.6) )300 –
SK-MEL-28 6.55 (2.49) 164 (11) 199 (11) –
5637 91.56 (2.21) 90.8 (3.2) 131.3 (1.0) –
Cytotoxicity of crude extracts (average of four replicates) are expressed as% kill at 250 mgyml except for 5637 cells, which were screened at 125 mgy ml. Cytotoxicity of 1 and 2 are IC50 values (mM). Standard deviations are shown in parentheses.
A.I. Rea et al. / Fitoterapia 74 (2003) 732–735
Table 1 Cytotoxic activitya of O. insignis bark extract, anacardic acid, and ginkoic acid
A.I. Rea et al. / Fitoterapia 74 (2003) 732–735
735
comparison of 1H and 13C NMR with those reported in the literature w6,7x. Cytotoxic activities are summarized in Table 1. Conclusions. Anacardic acid (1) and ginkgoic acid (2) are responsible for the cytotoxic activity of O. insignis bark extract, and this activity complements the biological activity observed in anacardic acids w4,8–14x. Acknowledgments Financial support: National Institutes of Health, Grant No. R15 GM57646-01A, (to ETG); the Research Board of the University of Zimbabwe, Grant No. 3YYH10y 3511 (to SS); and Research Genetics, Inc (to WNS). Traditional medical practitioners: Mr Nyoni of Mbizingwe under Chief Francis Mthonzima Gwebu of Umzingwane District and Mrs Ndule Sibanda of Nkayi District under Chief Madliwa Khumalo. Botanical identification: the late Mr Stephen Mavi (National Herbarium and Botanic Garden). Collection site: National Herbarium and Botanic Garden Nature Reserve. References w1x Gelfand M, Mavi S, Drummond RB, Ndemera B. The traditional medical practitioner in Zimbabwe. Gweru, Zimbabwe: Mambo Press, 1985. w2x Ndamba J, Nyazema N, Makaza N, Anderson C, Kaondera KC. J Ethnopharmacol 1994;42:125. w3x Molgaard P, Nielsen SB, Rasmussen DE, Drummond RB, Makaza N, Andreassen J. J Ethnopharmacol 2001;74:257. w4x He W, Van Puyvelde L, Bosselaers J, De Kimpe N, Van der Flaas M, Roymans A, et al. Pharm Biol 2002;40:74. w5x Setzer MC, Setzer WN, Jackes BR, Gentry GA, Moriarity DM. Pharm Biol 2001;39:67. w6x Gonzalez MJTG, DeOliviera CJC, Fernandes JO, Kijjoa A, Herz W. Phytochemistry 1996;43:1333. w7x Furstner ¨ A, Seidel G. J Org Chem 1997;62:2332. w8x Kubo I, Ochi M, Vieira PC, Komatsu S. J Agric Food Chem 1993;41:1012. w9x Muroi H, Kubo I. J Appl Bacteriol 1996;80:387. w10x Kubo J, Lee JR, Kubo I. J Agric Food Chem 1999;47:533. w11x Grazzini R, Hesk D, Heininger E, Hildenbrandt G, Reddy CC, Cox-Foster D, et al. Biochem Biophys Res Commun 1991;176:775. w12x Kubo I, Kinst-Hori I, Yokokawa Y. J Nat Prod 1994;57:545. w13x Shobha SV, Ramadoss CS, Ravindranath B. J Nat Prod 1994;57:1755. w14x Toyomizu M, Okamoto K, Ishibashi T, Chen Z, Nakatsu T. Life Sci 2000;66:229.