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Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Natural products isolated from Tetragonula carbonaria cerumen modulate free radical-scavenging and 5-lipoxygenase activities in vitro

Authors: Karina D. Hamilton, Peter R. Brooks, Steven M. Ogbourne, Fraser D. Russell

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Propolis and cerumen are plant-derived products found in honeybees and stingless bees, respectively. Although propolis is an ancient folk medicine, the bioactivities of cerumen obtained from Australian native stingless bees (Tetragonula carbonaria) have not been widely studied. Therefore, we investigated selected anti-oxidant and anti-inflammatory properties of T. carbonaria cerumen.

Methods

A methanolic extract was prepared from the combined cerumen of 40 T. carbonaria hives, and HPLC was used to screen for chemical constituents that scavenged 2,2-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The ability of cerumen extracts to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and to interfere with leukotriene B4 (LTB4) production in ionomycin-stimulated human neutrophils was also examined.

Results

The extract dose-dependently scavenged DPPH (EC50 = 27.0 ± 2.3 μg/mL); and inhibited the 5-lipoxygenase (5-LOX)-mediated oxidation of linoleic acid (IC50 = 67.1 ± 9.6 μg/mL). Pre-treatment of isolated human neutrophils with the methanolic cerumen extract additionally inhibited the ionomycin-stimulated production of LTB4 from these cells (IC50 = 13.3 ± 5.3 μg/mL). Following multi-solvent extraction, the free radical-scavenging and 5-LOX-inhibiting activities of the initial cerumen extract were retained in a polar, methanol-water extract, which contained gallic acid and a range of flavonone and phenolic natural products.

Conclusions

The findings identify free radical scavenging activity, and interference by extracts of T. carbonaria cerumen in 5-LOX–LTB4 signaling. Further investigation is needed to determine whether the extracts will provide therapeutic benefits for medical conditions in which oxidative stress and inflammation are implicated, including cardiovascular disease and impaired wound healing.
Literature
1.
go back to reference Toreti VC, Sato HH, Pastore GM, Park YK. Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evid-Based Complement Alternat Med. 2013;2013:697390.CrossRefPubMedPubMedCentral Toreti VC, Sato HH, Pastore GM, Park YK. Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evid-Based Complement Alternat Med. 2013;2013:697390.CrossRefPubMedPubMedCentral
2.
go back to reference Simone-Finstrom M, Spivak M. Propolis and bee health: the natural history and significance of resin use by honey bees. Apidologie. 2010;41:295–311.CrossRef Simone-Finstrom M, Spivak M. Propolis and bee health: the natural history and significance of resin use by honey bees. Apidologie. 2010;41:295–311.CrossRef
3.
go back to reference Castaldo S, Capasso F. Propolis, an old remedy used in modern medicine. Fitoterapia. 2002;73:S1–6.CrossRefPubMed Castaldo S, Capasso F. Propolis, an old remedy used in modern medicine. Fitoterapia. 2002;73:S1–6.CrossRefPubMed
4.
go back to reference Sforcin JM, Bankova V. Propolis: is there potential for the development of new drugs? J Ethnopharmacol. 2011;133:253–60.CrossRefPubMed Sforcin JM, Bankova V. Propolis: is there potential for the development of new drugs? J Ethnopharmacol. 2011;133:253–60.CrossRefPubMed
5.
go back to reference Kumazawa S, Hamasaka T, Nakayama T. Antioxidant activity of propolis of various geographic origins. Food Chem. 2004;84:329–39.CrossRef Kumazawa S, Hamasaka T, Nakayama T. Antioxidant activity of propolis of various geographic origins. Food Chem. 2004;84:329–39.CrossRef
6.
go back to reference Iyyam Pillai S, Palsamy P, Subramanian S, Kandaswamy M. Wound healing properties of Indian propolis studied on excision wound-induced rats. Pharm Biol. 2010;48:1198–206.CrossRefPubMed Iyyam Pillai S, Palsamy P, Subramanian S, Kandaswamy M. Wound healing properties of Indian propolis studied on excision wound-induced rats. Pharm Biol. 2010;48:1198–206.CrossRefPubMed
7.
go back to reference de Moura SAL, Negri G, Salatino A, Lima LD, Dourado LP, Mendes JB, Andrade SP, Ferreira MA, Cara DC. Aqueous extract of Brazilian green propolis: primary components, evaluation of inflammation and wound healing by using subcutaneous implanted sponges. Evid-Based Complement Alternat Med. 2011;2011:748283.PubMedPubMedCentral de Moura SAL, Negri G, Salatino A, Lima LD, Dourado LP, Mendes JB, Andrade SP, Ferreira MA, Cara DC. Aqueous extract of Brazilian green propolis: primary components, evaluation of inflammation and wound healing by using subcutaneous implanted sponges. Evid-Based Complement Alternat Med. 2011;2011:748283.PubMedPubMedCentral
8.
go back to reference Massaro CF, Simpson JB, Powell D, Brooks P. Chemical composition and antimicrobial activity of honeybee (Apis mellifera ligustica) propolis from subtropical eastern Australia. Sci Nat. 2015a;120:86. Massaro CF, Simpson JB, Powell D, Brooks P. Chemical composition and antimicrobial activity of honeybee (Apis mellifera ligustica) propolis from subtropical eastern Australia. Sci Nat. 2015a;120:86.
9.
go back to reference Petrova A, Popova M, Kuzmanova C, Tsvetkova I, Naydenski H, Muli E, Bankova V. New biologically active compounds from Kenyan propolis. Fitoterapia. 2010;81:509–14.CrossRefPubMed Petrova A, Popova M, Kuzmanova C, Tsvetkova I, Naydenski H, Muli E, Bankova V. New biologically active compounds from Kenyan propolis. Fitoterapia. 2010;81:509–14.CrossRefPubMed
10.
go back to reference Oldoni TLC, Cabral ISR, Regitano d'Arce MAB, Rosalen PL, Ikegaki M, Nascimento AM, Alencar SM. Isolation and analysis of bioactive isoflavonoids and chalcone from a new type of Brazilian propolis. Separ Purif Technol. 2011;77:208–13.CrossRef Oldoni TLC, Cabral ISR, Regitano d'Arce MAB, Rosalen PL, Ikegaki M, Nascimento AM, Alencar SM. Isolation and analysis of bioactive isoflavonoids and chalcone from a new type of Brazilian propolis. Separ Purif Technol. 2011;77:208–13.CrossRef
11.
go back to reference Abu-Mellal A, Koolaji N, Duke RK, Tran VH, Duke CC. Prenylated cinnamate and stilbenes from Kangaroo Island propolis and their antioxidant activity. Phytochemistry. 2012;77:251–9.CrossRefPubMed Abu-Mellal A, Koolaji N, Duke RK, Tran VH, Duke CC. Prenylated cinnamate and stilbenes from Kangaroo Island propolis and their antioxidant activity. Phytochemistry. 2012;77:251–9.CrossRefPubMed
12.
go back to reference Koolaji N, Abu-Mellal A, Tran VH, Duke RK, Duke CC. Synthesis of C- and O-prenylated tetrahydroxystilbenes and O-prenylated cinnamates and their action towards cancer cells. Eur J Med Chem. 2013;63:415–22.CrossRefPubMed Koolaji N, Abu-Mellal A, Tran VH, Duke RK, Duke CC. Synthesis of C- and O-prenylated tetrahydroxystilbenes and O-prenylated cinnamates and their action towards cancer cells. Eur J Med Chem. 2013;63:415–22.CrossRefPubMed
13.
go back to reference Dollin AE, Dollin LJ, Sakagami SF. Australian stingless bees of the genus Trigona (Hymenoptera: Apidae). Invertebr Taxon. 1997;11:861–96.CrossRef Dollin AE, Dollin LJ, Sakagami SF. Australian stingless bees of the genus Trigona (Hymenoptera: Apidae). Invertebr Taxon. 1997;11:861–96.CrossRef
14.
go back to reference Milborrow BV, Kennedy JM, Dollin A. Composition of wax made by the Australian stingless bee Trigona australis. Aust J Biol Sci. 1987;40:15–25. Milborrow BV, Kennedy JM, Dollin A. Composition of wax made by the Australian stingless bee Trigona australis. Aust J Biol Sci. 1987;40:15–25.
15.
go back to reference Wallace HM, Trueman SJ. Dispersal of Eucalyptus torelliana seeds by the resin-collecting stingless bee, Trigona carbonaria. Oecologia. 1995;104:12–6.CrossRefPubMed Wallace HM, Trueman SJ. Dispersal of Eucalyptus torelliana seeds by the resin-collecting stingless bee, Trigona carbonaria. Oecologia. 1995;104:12–6.CrossRefPubMed
16.
go back to reference Leonhardt SD, Wallace HM, Schmitt T. The cuticular profiles of Australian stingless bees are shaped by resin of the eucalypt tree Corymbia torelliana. Austral Ecol. 2011;36:537–43.CrossRef Leonhardt SD, Wallace HM, Schmitt T. The cuticular profiles of Australian stingless bees are shaped by resin of the eucalypt tree Corymbia torelliana. Austral Ecol. 2011;36:537–43.CrossRef
17.
go back to reference Massaro FC, Brooks PR, Wallace HM, Russell FD. Cerumen of Australian stingless bees (Tetragonula carbonaria): gas chromatography-mass spectrometry fingerprints and potential anti-inflammatory properties. Naturwissenschaften. 2011;98:329–37.CrossRefPubMed Massaro FC, Brooks PR, Wallace HM, Russell FD. Cerumen of Australian stingless bees (Tetragonula carbonaria): gas chromatography-mass spectrometry fingerprints and potential anti-inflammatory properties. Naturwissenschaften. 2011;98:329–37.CrossRefPubMed
18.
go back to reference Massaro CF, Katouli M, Grkovic T, Vu H, Quinn RJ, Heard TA, Carvalho C, Manley-Harris M, Wallace HM, Brooks P. Anti-staphylococcal activity of C-methyl flavanones from propolis of Australian stingless bees (Tetragonula carbonaria) and fruit resins of Corymbia torelliana (Myrtaceae). Fitoterapia. 2014;95:247–57.CrossRefPubMed Massaro CF, Katouli M, Grkovic T, Vu H, Quinn RJ, Heard TA, Carvalho C, Manley-Harris M, Wallace HM, Brooks P. Anti-staphylococcal activity of C-methyl flavanones from propolis of Australian stingless bees (Tetragonula carbonaria) and fruit resins of Corymbia torelliana (Myrtaceae). Fitoterapia. 2014;95:247–57.CrossRefPubMed
19.
go back to reference Massaro CF, Smyth TJ, Smyth WF, Heard T, Leonhardt SD, Katouli M, Wallace HM, Brooks P. Phloroglucinols from anti-microbial deposit-resins of Australian stingless bees (Tetragonula carbonaria). Phytother Res. 2015b;29:48–58.CrossRefPubMed Massaro CF, Smyth TJ, Smyth WF, Heard T, Leonhardt SD, Katouli M, Wallace HM, Brooks P. Phloroglucinols from anti-microbial deposit-resins of Australian stingless bees (Tetragonula carbonaria). Phytother Res. 2015b;29:48–58.CrossRefPubMed
20.
go back to reference Massaro FC, Brooks PR, Wallace HM, Nsengiyumva V, Narokai L, Russell FD. Effect of Australian propolis from stingless bees (Tetragonula carbonaria) on pre-contracted human and porcine isolated arteries. PLoS One. 2013;8:e81297.CrossRefPubMedPubMedCentral Massaro FC, Brooks PR, Wallace HM, Nsengiyumva V, Narokai L, Russell FD. Effect of Australian propolis from stingless bees (Tetragonula carbonaria) on pre-contracted human and porcine isolated arteries. PLoS One. 2013;8:e81297.CrossRefPubMedPubMedCentral
21.
go back to reference Zhang YP, Shi SY, Xiong X, Chen XQ, Peng MJ. Comparative evaluation of three methods based on high-performance liquid chromatography analysis combined with a 2,2′-diphenyl-1-picrylhydrazyl assay for the rapid screening of antioxidants from Pueraria lobata flowers. Anal Bioanal Chem. 2012;402:2965–76.CrossRefPubMed Zhang YP, Shi SY, Xiong X, Chen XQ, Peng MJ. Comparative evaluation of three methods based on high-performance liquid chromatography analysis combined with a 2,2′-diphenyl-1-picrylhydrazyl assay for the rapid screening of antioxidants from Pueraria lobata flowers. Anal Bioanal Chem. 2012;402:2965–76.CrossRefPubMed
22.
go back to reference Anthon GE, Barrett DM. Colorimetric method for the determination of lipoxygenase activity. J Agr Food Chem. 2001;49:32–7.CrossRef Anthon GE, Barrett DM. Colorimetric method for the determination of lipoxygenase activity. J Agr Food Chem. 2001;49:32–7.CrossRef
23.
go back to reference Russell FD, Windegger T, Hamilton KD, Cheetham NWH. Effect of the novel wound healing agent, OPAL A on leukotriene B4 production in human neutrophils and 5-lipoxygenase activity. Wound Pract Res. 2011;19:200–3. Russell FD, Windegger T, Hamilton KD, Cheetham NWH. Effect of the novel wound healing agent, OPAL A on leukotriene B4 production in human neutrophils and 5-lipoxygenase activity. Wound Pract Res. 2011;19:200–3.
24.
go back to reference Daleprane JB, Abdalla DS. Emerging roles of propolis: antioxidant, cardioprotective, and antiangiogenic actions. Evid-Based Complement Alternat Med. 2013;2013:175135.CrossRefPubMedPubMedCentral Daleprane JB, Abdalla DS. Emerging roles of propolis: antioxidant, cardioprotective, and antiangiogenic actions. Evid-Based Complement Alternat Med. 2013;2013:175135.CrossRefPubMedPubMedCentral
25.
go back to reference Gregoris E, Stevanato R. Correlations between polyphenolic composition and antioxidant activity of venetian propolis. Food Chem Toxicol. 2010;48:76–82.CrossRefPubMed Gregoris E, Stevanato R. Correlations between polyphenolic composition and antioxidant activity of venetian propolis. Food Chem Toxicol. 2010;48:76–82.CrossRefPubMed
26.
go back to reference Gülçin İ, Bursal E, Şehitoğlu MH, Bilsel M, Gören AC. Polyphenol contents and antioxidant activity of lyophilized aqueous extract of propolis from Erzurum. Turkey Food Chem Toxicol. 2010;48:2227–38.CrossRefPubMed Gülçin İ, Bursal E, Şehitoğlu MH, Bilsel M, Gören AC. Polyphenol contents and antioxidant activity of lyophilized aqueous extract of propolis from Erzurum. Turkey Food Chem Toxicol. 2010;48:2227–38.CrossRefPubMed
27.
go back to reference Teixeira ÉW, Message D, Negri G, Salatino A, Stringheta PC. Seasonal variation, chemical composition and antioxidant activity of Brazilian propolis samples. Evid-Based Complement Alternat Med. 2010;7:307–15.CrossRefPubMed Teixeira ÉW, Message D, Negri G, Salatino A, Stringheta PC. Seasonal variation, chemical composition and antioxidant activity of Brazilian propolis samples. Evid-Based Complement Alternat Med. 2010;7:307–15.CrossRefPubMed
28.
go back to reference Mello BCB, Hubinger MD. Antioxidant activity and polyphenol contents in Brazilian green propolis extracts prepared with the use of ethanol and water as solvents in different pH values. Int J Food Sci Technol. 2012;47:2510–8.CrossRef Mello BCB, Hubinger MD. Antioxidant activity and polyphenol contents in Brazilian green propolis extracts prepared with the use of ethanol and water as solvents in different pH values. Int J Food Sci Technol. 2012;47:2510–8.CrossRef
29.
go back to reference da Silva Frozza CO, Garcia CSC, Gambato G, de Souza MDO, Salvador M, Moura S, Padilha FF, Seixas FK, Collares T, Borsuk S, Dellagostin OA, Henriques JAP, Roesch-Ely M. Chemical characterization, antioxidant and cytotoxic activities of Brazilian red propolis. Food Chem Toxicol. 2013;52:137–42.CrossRef da Silva Frozza CO, Garcia CSC, Gambato G, de Souza MDO, Salvador M, Moura S, Padilha FF, Seixas FK, Collares T, Borsuk S, Dellagostin OA, Henriques JAP, Roesch-Ely M. Chemical characterization, antioxidant and cytotoxic activities of Brazilian red propolis. Food Chem Toxicol. 2013;52:137–42.CrossRef
30.
go back to reference Campos JF, dos Santos UP, Macorini LFB, de Melo AMMF, Balestieri JBP, Paredes-Gamero EJ, Cardoso CAL, de Picoli SK, dos Santos EL. Antimicrobial, antioxidant and cytotoxic activities of propolis from Melipona orbignyi (Hymenoptera, Apidae). Food Chem Toxicol. 2014;65:374–80.CrossRefPubMed Campos JF, dos Santos UP, Macorini LFB, de Melo AMMF, Balestieri JBP, Paredes-Gamero EJ, Cardoso CAL, de Picoli SK, dos Santos EL. Antimicrobial, antioxidant and cytotoxic activities of propolis from Melipona orbignyi (Hymenoptera, Apidae). Food Chem Toxicol. 2014;65:374–80.CrossRefPubMed
31.
go back to reference Souza SA, Dias TLMF, Silva TMG, Falcão RA, Alexandre-Moreira MS, Silva EMS, Camara CA, Silva TMS. Chemical composition, antinociceptive and free radical-scavenging activities of geopropolis from Melipona subnitida Ducke (Hymenoptera: Apidae: Meliponini). Sociobiol. 2014;61:560–5. Souza SA, Dias TLMF, Silva TMG, Falcão RA, Alexandre-Moreira MS, Silva EMS, Camara CA, Silva TMS. Chemical composition, antinociceptive and free radical-scavenging activities of geopropolis from Melipona subnitida Ducke (Hymenoptera: Apidae: Meliponini). Sociobiol. 2014;61:560–5.
32.
go back to reference Sud'ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett. 1993;329:21–4.CrossRefPubMed Sud'ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett. 1993;329:21–4.CrossRefPubMed
33.
go back to reference Boudreau LH, Maillet J, LeBlanc LM, Jean-François J, Touaibia M, Flamand N, Surette ME. Caffeic acid phenethyl ester and its amide analogue are potent inhibitors of leukotriene biosynthesis in human polymorphonuclear leukocytes. PLoS One. 2012;7:e31833.CrossRefPubMedPubMedCentral Boudreau LH, Maillet J, LeBlanc LM, Jean-François J, Touaibia M, Flamand N, Surette ME. Caffeic acid phenethyl ester and its amide analogue are potent inhibitors of leukotriene biosynthesis in human polymorphonuclear leukocytes. PLoS One. 2012;7:e31833.CrossRefPubMedPubMedCentral
34.
go back to reference Kim C, Kim J, Kim J. Cytosolic phosopholipase A2, lipoxygenase metabolites, and reactive oxygen species. BMB Rep. 2008;41:555–9.CrossRefPubMed Kim C, Kim J, Kim J. Cytosolic phosopholipase A2, lipoxygenase metabolites, and reactive oxygen species. BMB Rep. 2008;41:555–9.CrossRefPubMed
35.
36.
go back to reference Tani H, Hasumi K, Tatefuji T, Hashimoto K, Koshino H, Takahashi S. Inhibitory activity of Brazilian green propolis components and their derivatives on the release of cys-leukotrienes. Bioorg Med Chem. 2010;18:151–7.CrossRefPubMed Tani H, Hasumi K, Tatefuji T, Hashimoto K, Koshino H, Takahashi S. Inhibitory activity of Brazilian green propolis components and their derivatives on the release of cys-leukotrienes. Bioorg Med Chem. 2010;18:151–7.CrossRefPubMed
37.
go back to reference Mirzoeva OK, Calder PC. The effect of propolis and its components on eicosanoid production during the inflammatory response. Prostag Leukotr Ess. 1996;55:441–9.CrossRef Mirzoeva OK, Calder PC. The effect of propolis and its components on eicosanoid production during the inflammatory response. Prostag Leukotr Ess. 1996;55:441–9.CrossRef
Metadata
Title
Natural products isolated from Tetragonula carbonaria cerumen modulate free radical-scavenging and 5-lipoxygenase activities in vitro
Authors
Karina D. Hamilton
Peter R. Brooks
Steven M. Ogbourne
Fraser D. Russell
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1748-6

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