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Published in: BMC Complementary Medicine and Therapies 1/2014

Open Access 01-12-2014 | Research article

Antimicrobial activity, toxicity and selectivity index of two biflavonoids and a flavone isolated from Podocarpus henkelii (Podocarpaceae) leaves

Authors: Victor P Bagla, Lyndy J McGaw, Esam E Elgorashi, Jacobus N Eloff

Published in: BMC Complementary Medicine and Therapies | Issue 1/2014

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Abstract

Background

Different parts of Podocarpus henkelii have been used in many cultures around the world to treat ailments such as cholera, stomach diseases, rheumatism, cancer, canine distemper in dogs and gall sickness in cattle. The aim of this study was to evaluate the biological activity and toxicity of isolated compounds from Podocarpus henkelii after an earlier study indicated a promising activity in crude extracts against viral pathogens of veterinary importance.

Methods

The antibacterial and antifungal activity of two biflavonoids 7, 4’, 7”, 4”’-tetramethoxy amentoflavone (TMA), isoginkgetin (IGG) and podocarpus flavone–A (PFA) isolated from the leaves of Podocarpus henkelii were determined using a serial microplate dilution method with tetrazolium violet as growth indicator. The cytotoxicity of compounds TMA and IGG were determined on different cell types using a tetrazolium-based colorimetric cellular assay (MTT). The Ames test was used to determine their mutagenic activities.

Results

TMA had reasonable antifungal activity against Aspergillus fumigatus (MIC = 30 μg/ml). IGG had a wide spectrum of activity against four bacterial and two fungal pathogens with much higher selectivity index values obtained for A. fumigatus and Cryptococcus neoformans (SI > 30). PFA had a broad spectrum of activity against Enterococcus faecalis and Pseudomonas aeruginosa (SI > 15) and less activity against the two fungal pathogens. In both the cytotoxicity assays and Ames mutagenicity test using Salmonella typhimurium strains TA98 and TA100, TMA and IGG had no deleterious effect on the different cell types and did not induce mutations in the Ames test.

Conclusion

Although the antimicrobial activities of the isolated compounds were not that exciting, the compounds had no cytotoxic activity at the highest concentration (1000 μg/ml) tested against all three cell lines. IGG was the most active against E. coli, S. aureus, A. fumigatus and C. neoformans, exhibiting both antibacterial and antifungal activity with good selectivity index values. PFA had a broad spectrum of activity against E. faecalis and P. aeruginosa. The two compounds isolated had low toxicity and no genotoxic activity in the Ames test.
Literature
1.
go back to reference Smith CJ: Accumulation of phytoalexins: defence mechanism and stimulus response system. New Phytol. 1996, 132: 1-45. 10.1111/j.1469-8137.1996.tb04506.x.CrossRef Smith CJ: Accumulation of phytoalexins: defence mechanism and stimulus response system. New Phytol. 1996, 132: 1-45. 10.1111/j.1469-8137.1996.tb04506.x.CrossRef
2.
go back to reference Beecher GR: Overview of Dietary Flavonoids: Nomenclature Occurrence and Intake. Journal of Nutrition. 2003, 133: 3248- Beecher GR: Overview of Dietary Flavonoids: Nomenclature Occurrence and Intake. Journal of Nutrition. 2003, 133: 3248-
3.
go back to reference Grange JM, Davey RW: Antibacterial properties of propolis (bee glue). J Royal Soc Med. 1990, 83: 159-160. Grange JM, Davey RW: Antibacterial properties of propolis (bee glue). J Royal Soc Med. 1990, 83: 159-160.
4.
go back to reference Middleton E, Chithan K: The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. The Flavonoids: Advances in research since 1986. Edited by: Harborne JB. 1993, London: Chapman and Hall, 619-652.CrossRef Middleton E, Chithan K: The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. The Flavonoids: Advances in research since 1986. Edited by: Harborne JB. 1993, London: Chapman and Hall, 619-652.CrossRef
5.
go back to reference Kang SS, Lee JY, Choi YK, Song SS, Kim JS, Jeon SJ, Han YN, Son KH, Han BH: Neuroprotective effects of naturally occurring biflavonoids. Bioorganic and Medicinal Chemistry Letters. 2005, 15: 3588-3591. 10.1016/j.bmcl.2005.05.078.CrossRefPubMed Kang SS, Lee JY, Choi YK, Song SS, Kim JS, Jeon SJ, Han YN, Son KH, Han BH: Neuroprotective effects of naturally occurring biflavonoids. Bioorganic and Medicinal Chemistry Letters. 2005, 15: 3588-3591. 10.1016/j.bmcl.2005.05.078.CrossRefPubMed
6.
go back to reference Mbwambo ZH, Kapingu MC, Moshi MJ, Francis M, Apers S, Cos P, Ferreira D, Marais JPJ, Vanden Berghe D, Maes L, Vlietinck A, Pieters L: Antiparasitic activity of some xanthones and biflavonoids from the root bark of Garcinia livingstonei. J Nat Prod. 2006, 69: 369-372. 10.1021/np050406v.CrossRefPubMed Mbwambo ZH, Kapingu MC, Moshi MJ, Francis M, Apers S, Cos P, Ferreira D, Marais JPJ, Vanden Berghe D, Maes L, Vlietinck A, Pieters L: Antiparasitic activity of some xanthones and biflavonoids from the root bark of Garcinia livingstonei. J Nat Prod. 2006, 69: 369-372. 10.1021/np050406v.CrossRefPubMed
7.
go back to reference Yamaguchi LF, Vassao DG, Kato MJ, Mascio PD: Biflavonoids from Brazilian pine Araucaria angustifolia as potentials protective agents against DNA damage and lipoperoxidation. Phytochemistry. 2005, 66: 2238-2247. 10.1016/j.phytochem.2004.11.014.CrossRefPubMed Yamaguchi LF, Vassao DG, Kato MJ, Mascio PD: Biflavonoids from Brazilian pine Araucaria angustifolia as potentials protective agents against DNA damage and lipoperoxidation. Phytochemistry. 2005, 66: 2238-2247. 10.1016/j.phytochem.2004.11.014.CrossRefPubMed
8.
go back to reference Lin YM, Anderson H, Flavin MT, Pai YHS, Greenwood EM, Pengsuparp TJM, Pezzuto RF, Schinazi Hughes SH, Chen FC: In vitro anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora. J Nat Prod. 1997, 60: 884-10.1021/np9700275.CrossRefPubMed Lin YM, Anderson H, Flavin MT, Pai YHS, Greenwood EM, Pengsuparp TJM, Pezzuto RF, Schinazi Hughes SH, Chen FC: In vitro anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora. J Nat Prod. 1997, 60: 884-10.1021/np9700275.CrossRefPubMed
9.
go back to reference Miki K, Nagai T, Suzuki K, Tsujimura R, Koyama K, Kinoshita K, Furuhata K, Yamada H, Takahashi K: Anti-influenza virus activity of biflavonoids. Bioorganic and Medicinal Chem Lett. 2007, 17: 772-775. 10.1016/j.bmcl.2006.10.075.CrossRef Miki K, Nagai T, Suzuki K, Tsujimura R, Koyama K, Kinoshita K, Furuhata K, Yamada H, Takahashi K: Anti-influenza virus activity of biflavonoids. Bioorganic and Medicinal Chem Lett. 2007, 17: 772-775. 10.1016/j.bmcl.2006.10.075.CrossRef
10.
go back to reference Lin YM, Flavin MT, Cassidy CS, Mar A, Chen FC: Biflavonoids as novel antituberculosis agents. Bioorganic and Medicinal Chem Lett. 2001, 11: 2101-2104. 10.1016/S0960-894X(01)00382-1.CrossRef Lin YM, Flavin MT, Cassidy CS, Mar A, Chen FC: Biflavonoids as novel antituberculosis agents. Bioorganic and Medicinal Chem Lett. 2001, 11: 2101-2104. 10.1016/S0960-894X(01)00382-1.CrossRef
11.
go back to reference Xu HX, Lee SF: Activity of plant flavonoids against antibiotic-resistant bacteria. Phytother Res. 2001, 15: 39-43. 10.1002/1099-1573(200102)15:1<39::AID-PTR684>3.0.CO;2-R.CrossRefPubMed Xu HX, Lee SF: Activity of plant flavonoids against antibiotic-resistant bacteria. Phytother Res. 2001, 15: 39-43. 10.1002/1099-1573(200102)15:1<39::AID-PTR684>3.0.CO;2-R.CrossRefPubMed
12.
go back to reference Yenjai C, Prasanphen K, Daodee S, Wongpanich V, Kittakoop P: Bioactive flavonoids from Kaempferia parviflora. Fitoterapia. 2004, 75: 89-92. 10.1016/j.fitote.2003.08.017.CrossRefPubMed Yenjai C, Prasanphen K, Daodee S, Wongpanich V, Kittakoop P: Bioactive flavonoids from Kaempferia parviflora. Fitoterapia. 2004, 75: 89-92. 10.1016/j.fitote.2003.08.017.CrossRefPubMed
13.
go back to reference Martini ND, Katerere DRP, Eloff JN: Biological activity of five antibacterial flavonoids from Combretum erythrophyllum (Combretaceae). J Ethnopharmacol. 2004, 93: 207-212. 10.1016/j.jep.2004.02.030.CrossRefPubMed Martini ND, Katerere DRP, Eloff JN: Biological activity of five antibacterial flavonoids from Combretum erythrophyllum (Combretaceae). J Ethnopharmacol. 2004, 93: 207-212. 10.1016/j.jep.2004.02.030.CrossRefPubMed
14.
go back to reference Selvam C, Jachak SM: A cyclooxygenase (COX) inhibitory biflavonoid from the seeds of Semecarpus anacardium. J Ethnopharmacol. 2004, 95: 209-212. 10.1016/j.jep.2004.07.026.CrossRefPubMed Selvam C, Jachak SM: A cyclooxygenase (COX) inhibitory biflavonoid from the seeds of Semecarpus anacardium. J Ethnopharmacol. 2004, 95: 209-212. 10.1016/j.jep.2004.07.026.CrossRefPubMed
15.
go back to reference Cardoso CL, Silva DHS, Castro-Gamboa I, Bolzani VDS: New biflavonoid and other flavonoids from the leaves of Chimarrhis turbinate and their antioxidant activities. J Brazillian Chemical Soc. 2005, 16: 1353-1359. 10.1590/S0103-50532005000800008.CrossRef Cardoso CL, Silva DHS, Castro-Gamboa I, Bolzani VDS: New biflavonoid and other flavonoids from the leaves of Chimarrhis turbinate and their antioxidant activities. J Brazillian Chemical Soc. 2005, 16: 1353-1359. 10.1590/S0103-50532005000800008.CrossRef
16.
go back to reference Rizvi SHM, Rahman W, Okigawa M, Kawano N: Biflavones from Podocarpus neriifolius. Phytochemistry. 1974, 13: 1990-10.1016/0031-9422(74)85132-0.CrossRef Rizvi SHM, Rahman W, Okigawa M, Kawano N: Biflavones from Podocarpus neriifolius. Phytochemistry. 1974, 13: 1990-10.1016/0031-9422(74)85132-0.CrossRef
17.
go back to reference Hodges R: 5,5'-dihydroxy-7,4',7"4"'-tetramethoxy-8,31'1-biflavone from Dacrydium cupressiatum Lamb. Aust J Chem. 1965, 18: 1491-1492. 10.1071/CH9651491.CrossRef Hodges R: 5,5'-dihydroxy-7,4',7"4"'-tetramethoxy-8,31'1-biflavone from Dacrydium cupressiatum Lamb. Aust J Chem. 1965, 18: 1491-1492. 10.1071/CH9651491.CrossRef
18.
go back to reference Weniger B, Vonthron-Se’ne’cheau C, Kaiser M, Brun R, Anton R: Comparative antiplasmodial, leishmanicidal and antitrypanosomal activities of several biflavonoids. Phytomedicine. 2006, 13: 176-180. 10.1016/j.phymed.2004.10.008.CrossRefPubMed Weniger B, Vonthron-Se’ne’cheau C, Kaiser M, Brun R, Anton R: Comparative antiplasmodial, leishmanicidal and antitrypanosomal activities of several biflavonoids. Phytomedicine. 2006, 13: 176-180. 10.1016/j.phymed.2004.10.008.CrossRefPubMed
19.
go back to reference Yoon S, Sejeong S, Ho-Jae L, Hyo-Kon C, Chung A: Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt -dependent matrix metalloproteinase-9 expression. Mol Cancer Ther. 2006, 5: 2666-2675. 10.1158/1535-7163.MCT-06-0321.CrossRefPubMed Yoon S, Sejeong S, Ho-Jae L, Hyo-Kon C, Chung A: Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt -dependent matrix metalloproteinase-9 expression. Mol Cancer Ther. 2006, 5: 2666-2675. 10.1158/1535-7163.MCT-06-0321.CrossRefPubMed
20.
go back to reference O’Brien K, Matlin AJ, Lowell AM, Moore MJ: The Biflavonoid Isoginkgetin is a general inhibitor of pre-mRNA splicing. J Biological Chem. 2008, 283 (48): 33147-33154. 10.1074/jbc.M805556200.CrossRef O’Brien K, Matlin AJ, Lowell AM, Moore MJ: The Biflavonoid Isoginkgetin is a general inhibitor of pre-mRNA splicing. J Biological Chem. 2008, 283 (48): 33147-33154. 10.1074/jbc.M805556200.CrossRef
21.
go back to reference Eloff JN: A sensitive and quick method to determine the minimal inhibitory concentration of plant extracts for bacteria. Planta Med. 1998, 64: 711-713. 10.1055/s-2006-957563.CrossRefPubMed Eloff JN: A sensitive and quick method to determine the minimal inhibitory concentration of plant extracts for bacteria. Planta Med. 1998, 64: 711-713. 10.1055/s-2006-957563.CrossRefPubMed
22.
go back to reference Masoko P, Picard J, Eloff JN: Antifungal activities of six South African Terminalia species (Combretaceae). J Ethnopharmacol. 2005, 99: 301-308. 10.1016/j.jep.2005.01.061.CrossRefPubMed Masoko P, Picard J, Eloff JN: Antifungal activities of six South African Terminalia species (Combretaceae). J Ethnopharmacol. 2005, 99: 301-308. 10.1016/j.jep.2005.01.061.CrossRefPubMed
23.
go back to reference Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983, 65: 55-63. 10.1016/0022-1759(83)90303-4.CrossRefPubMed Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983, 65: 55-63. 10.1016/0022-1759(83)90303-4.CrossRefPubMed
24.
go back to reference Maron DM, Ames BN: Revised methods for the Salmonella mutagenicity test. Mutatagenesis Research. 1983, 113: 173-215.CrossRef Maron DM, Ames BN: Revised methods for the Salmonella mutagenicity test. Mutatagenesis Research. 1983, 113: 173-215.CrossRef
25.
go back to reference Nostro A, Germano MP, D’Angelo V, Marino A, Cannatelli MA: Extraction methods and bioautography for evaluation of medicinal plant antimicrobial activity. Lett Appl Microbiol. 2000, 30: 379-384. 10.1046/j.1472-765x.2000.00731.x.CrossRefPubMed Nostro A, Germano MP, D’Angelo V, Marino A, Cannatelli MA: Extraction methods and bioautography for evaluation of medicinal plant antimicrobial activity. Lett Appl Microbiol. 2000, 30: 379-384. 10.1046/j.1472-765x.2000.00731.x.CrossRefPubMed
26.
go back to reference Hodges N: Pharmaceutical applications of microbiological techniques. Pharmaceutics: The Science of Dosage Form Design. Edited by: Aulton ME. 2002, London: Harcourt Publishers Limited, 606-2 Hodges N: Pharmaceutical applications of microbiological techniques. Pharmaceutics: The Science of Dosage Form Design. Edited by: Aulton ME. 2002, London: Harcourt Publishers Limited, 606-2
27.
go back to reference Cushnie TPT, Lamb AJ: Antimicrobial activity of flavonoids. Int J Antimicrob Agents. 2005, 26: 343-356. 10.1016/j.ijantimicag.2005.09.002.CrossRefPubMed Cushnie TPT, Lamb AJ: Antimicrobial activity of flavonoids. Int J Antimicrob Agents. 2005, 26: 343-356. 10.1016/j.ijantimicag.2005.09.002.CrossRefPubMed
28.
go back to reference Harborne JB, Williams CA: Advances in flavonoid research since 1992. Phytochemistry. 2000, 55 (6): 481-504. 10.1016/S0031-9422(00)00235-1.CrossRefPubMed Harborne JB, Williams CA: Advances in flavonoid research since 1992. Phytochemistry. 2000, 55 (6): 481-504. 10.1016/S0031-9422(00)00235-1.CrossRefPubMed
29.
go back to reference Picman AK, Schneider EF, Pieman J: Effect of flavonoids on mycelial growth of Verticillium albo-atrum. Biochem Syst Ecol. 1995, 23: 683-693. 10.1016/0305-1978(95)00081-X.CrossRef Picman AK, Schneider EF, Pieman J: Effect of flavonoids on mycelial growth of Verticillium albo-atrum. Biochem Syst Ecol. 1995, 23: 683-693. 10.1016/0305-1978(95)00081-X.CrossRef
30.
go back to reference Gafner S, Wolfender JL, Mavi S, Hostettmann K: Antifungal and antibacterial chalcones from Myrica serrata. Planta Med. 1996, 62: 67-69. 10.1055/s-2006-957804.CrossRefPubMed Gafner S, Wolfender JL, Mavi S, Hostettmann K: Antifungal and antibacterial chalcones from Myrica serrata. Planta Med. 1996, 62: 67-69. 10.1055/s-2006-957804.CrossRefPubMed
31.
go back to reference Ames BN, McCann J, Yamazaki E: Methods for detecting carcinogens and mutagens with salmonella-mammalian microsome mutagenicity test. Mutagenesis Research. 1975, 31: 347-363. Ames BN, McCann J, Yamazaki E: Methods for detecting carcinogens and mutagens with salmonella-mammalian microsome mutagenicity test. Mutagenesis Research. 1975, 31: 347-363.
32.
go back to reference Habs M, Habs H, Berger MR, Schmahl D: Negative dose response study for carcinogenicity of orally administered rutin sulphate in Sprague-Dawley rats. Cancer Lett. 1984, 23: 103-108. 10.1016/0304-3835(84)90068-5.CrossRefPubMed Habs M, Habs H, Berger MR, Schmahl D: Negative dose response study for carcinogenicity of orally administered rutin sulphate in Sprague-Dawley rats. Cancer Lett. 1984, 23: 103-108. 10.1016/0304-3835(84)90068-5.CrossRefPubMed
33.
go back to reference Bent HH: The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002, 96: 67-202. 10.1016/S0163-7258(02)00298-X.CrossRef Bent HH: The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002, 96: 67-202. 10.1016/S0163-7258(02)00298-X.CrossRef
34.
go back to reference Kuo Y-J S-Y H, Wu M-D, Liao C-C, Liang Y-H, Kuo Y-H HOH-O: Cytotoxic Constituents from Podocarpus fasciculus. Chem Pharm Bulletin. 2008, 56 (4): 585-588. 10.1248/cpb.56.585.CrossRef Kuo Y-J S-Y H, Wu M-D, Liao C-C, Liang Y-H, Kuo Y-H HOH-O: Cytotoxic Constituents from Podocarpus fasciculus. Chem Pharm Bulletin. 2008, 56 (4): 585-588. 10.1248/cpb.56.585.CrossRef
Metadata
Title
Antimicrobial activity, toxicity and selectivity index of two biflavonoids and a flavone isolated from Podocarpus henkelii (Podocarpaceae) leaves
Authors
Victor P Bagla
Lyndy J McGaw
Esam E Elgorashi
Jacobus N Eloff
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2014
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-14-383

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