EXPLORING BEE VENOM VOLATILES: A PROMISING AVENUE FOR CYSTIC FIBROSIS
Yıl 2024,
, 267 - 284, 18.11.2024
Nilüfer Vural
,
Sibel Kaymak
,
Oğuz Yüce
Öz
Bee venom, a complex mixture of bioactive compounds, has demonstrated anti-inflammatory, antimicrobial, and immunomodulatory properties. Notably, the volatiles released by bee venom components have garnered attention for their potential in respiratory-related disease conditions. Cystic fibrosis (CF) is a challenging disorder, characterized by a genetic mutation affecting the CFTR protein, leading to the production of thick and sticky mucus in various organs, particularly the lungs and digestive system, and necessitating innovative therapeutic approaches. This research explored both bee venom volatiles’ chemical composition and the effects on airway inflammation and mucus viscosity in CF patients by in silico methods. GC/MS analyses with various SPME fibers have conducted the identification of 67 distinct components in volatile compounds of bee venom. For CW/DVB, CAR-PDMS, and DVB-PDMS fibers, the compounds identified in the highest amounts were perilla alcohol (42.21%), tetradecane (11.48%), and 1,2-benzenedicarboxylic acid, 1,2-bis(2-methylpropyl) ester (39.98%), respectively. In silico analyses subsequently indicated that these components exhibit anti-inflammatory effects by modulating key cytokines and reducing inflammatory markers in CF airways. This research highlights the potential of bee venom volatiles as a novel therapeutic avenue for managing CF symptoms. Harnessing the unique properties of bee venom may offer new perspectives in the development of targeted therapies for individuals affected by cystic fibrosis.
Etik Beyan
No experimentation on human or animal subjects was involved in this study. At the stage of bee venom sampling from honey bees, ethical permission is not required for insects. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Destekleyen Kurum
This research was supported by the Republic of Türkiye Ministry of Agriculture and Forestry General Directorate of Agriculture Research and Policies (TAGEM) with Project number: TAGEM/21/AR-GE/25.
Teşekkür
The authors would like to thank Harun ARSLAN from Ankara Yıldırım Beyazıt University GETAT Center Research Apiary for his help in the care and supply of bees, and Turan ÇIRAK, technical staff of the GETAT Center, for his help in the special hive design.
Kaynakça
- Abd El-Wahed AA, Farag MA, Eraqi WA, Mersal GAM, Zhao C, Khalifa SAM et al. Unravelling the beehive air volatiles profile as analysed via solid-phase microextraction (SPME) and chemometrics. Journal of King Saud University–Science, 2021;33:101449.
- Allen L, Carr SB, Davies G, Downey D, Egan M, Forton JT et al. Future therapies for cystic fibrosis. A.J.N.C., 2023;14:693.
- Barnes M, Brisbois EJ. Clinical use of inhaled nitric oxide: Local and systemic applications, J.F.R.B., 2020;152:422-431.
- Boch R, Shearer D, Stone BJN. Identification of iso-amyl acetate as an active component in the sting pheromone of the honey bee. Nature, 1962;195:1018-1020.
- Burley SK, Berman HM, Kleywegt GJ, Markley JL, Nakamura H., Velankar S. Protein Data Bank (PDB): the single global macromolecular structure archive. J.P.C.M., 2017;627-641.
- Camargos AF, Cossolin JFS, Martínez LC, Gonçalves WG, dos Santos MH, Zanuncio JC et al. Morphology and chemical composition of the Koschewnikow gland of the honey bee Apis mellifera (Hymenoptera: Apidae) workers engaged in different tasks. Journal of Apicultural Research, 2020;59:1037-1048.
- Castellani C, Assael BM. Cystic fibrosis: a clinical view. Cellular and molecular life sciences, 2017;74:129-140.
- Choi HS, Kang SY, Roh DH, Choi SR, Ryu Y, Lee JH. Bee venom stimulation of a lung meridian acupoint reduces inflammation in carrageenan-induced pleurisy: an alternative therapeutic approach for respiratory inflammation. .J.O.V.S.,2018;19:708-715.
- Cutting GR. Cystic fibrosis genetics: from molecular understanding to clinical application. J.N.R.G., 2015;16:45-56.
- Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. J.S.r., 2017;7:42717.
- de Graaf DC, Brochetto-Braga MR, de Abreu RMM, Blank S, Bridts CH., De Clerck LS et al. Standard methods for Apis mellifera venom research. Journal of Apicultural Research, 2021;60:1-31.
- de Lacy-Costello B, Amann A, Al-Kateb H, Flynn C, Filipiak W, Khalid T et al. A review of the volatiles from the healthy human body. J.O.B.R., 2014;8:014001.
- Dogru D, Çakır E, Şişmanlar T, Çobanoğlu N, Pekcan S, Çinel G et al. Cystic fibrosis in Turkey: First data from the national registry. J.P.P., 2020;55: 541-548.
- Fraser-Pitt D, O’Neil D. Cystic fibrosis–a multiorgan protein misfolding disease. Future science OA, 2015;1(2): DOI: 10.4155/fso.15.57.
- Fratellone PM, Tsimis F, Fratellone G. Apitherapy products for medicinal use.The Journal of Alternative and Complementary Medicine, 2016;22(12):1020-1022.
- Graeber SY, Mall MA. The future of cystic fibrosis treatment: from disease mechanisms to novel therapeutic approaches. J.T.L., 2023;402:1185-1198.
- Habryka C, Kruczek M, Drygaś B. Bee products used in apitherapy. J.W.S.N., 2016:254-258.
- Hasan A, Qazi JI, Tabssum F, Hussain A. Increased bee venom production in Apis mellifera workers on the provision of probiotics and organic acids. ISBAB, 2023;48.
- Isidorov V, Zalewski A, Zambrowski G, Swiecicka I. Chemical Composition and Antimicrobial Properties of Honey Bee Venom. Molecules, 2023;28:4135
- Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A et al. PubChem substance and compound databases J.N.a.r., 2016;44:1202-1213.
- Li J, Wang Z, Tan K, Qu Y, Nieh JC. Effects of natural and synthetic alarm pheromone and individual pheromone components on foraging behavior of the giant Asian honey bee, Apis dorsata. The Journal of experimental biology, 2014;217:3512-3518.
- Lillehoj EP, Kato K, Lu W, Kim KC. Cellular and molecular biology of airway mucins. J.I.R.O.C., 2013;(303):139-202.
- Matysiak J, Breborowicz A, Kycler Z, Derezinski P, Kokot ZJ. Immune and clinical response to honeybee venom in beekeepers. A.O.A., 2016;23.
- Maunz A, Gütlein M, Rautenberg M, Vorgrimmler D, Gebele D, Helma C. lazar: a modular predictive toxicology framework. Frontiers in pharmacology, 2013;4.
- Naehrig S, Chao CM, Naehrlich L. Cystic fibrosis: diagnosis and treatment. Deutsches Ärzteblatt International, 2017;114:33-34.
- Nakamura Y, Sugano A, Ohta M, Takaoka Y. Docking analysis and the possibility of prediction efficacy for an anti-IL-13 biopharmaceutical treatment with tralokinumab and lebrikizumab for bronchial asthma. J.P.O., 2017;12.
- Nikbakhtzadeh MR, Tirgari S, Fakoorziba MR, Alipour H. Two volatiles from the venom gland of the Samsum ant, Pachycondyla sennaarensis. Toxicon, 2009;54:80-82.
- Noël A, Dumas C, Rottier E, Beslay D, Costagliola G, Ginies C et al. Detailed chemical analysis of honey bee (Apis mellifera) worker brood volatile profile from egg to emergence. J.P.O., 2023;18.
- Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC et al. UCSF Chimera—a visualization system for exploratory research and analysis. J.O.C.C., 2004;25: 1605-1612.
- Samsuzzaman M, Uddin MS, Shah MA, Mathew B. Natural inhibitors on airway mucin: Molecular insight into the therapeutic potential targeting MUC5AC expression and production. J.L.s., 2019;231:116485.
- Schmitt T, Herzner G, Weckerle B, Schreier P, Strohm E. Volatiles of foraging honeybees Apis mellifera (Hymenoptera: Apidae) and their potential role as semiochemicals. J.A., 2007;38:164-170.
- Simone-Finstrom M, Angove M, Brooks P, Gerdts J. Identification and Discrimination of Volatiles Associated With Chalkbrood Infection in European Honey Bees (Apis mellifera), Eastern Australia. J.R.S., 2023;24.
- Stela M, Cichon N, Spławska A, Szyposzynska M, Bijak M. 2024. Therapeutic Potential and Mechanisms of Bee Venom Therapy: A Comprehensive Review of Apitoxin Applications and Safety Enhancement Strategies. Pharmaceuticals, 2024;17(9).
- Studio, Discovery studio. D.J.A., 2008.
- Topal E, Adamchuk L, Negri I, Kösoğlu M, Papa G, Dârjan MS et al. Traces of Honeybees, Api-Tourism and Beekeeping: From Past to Present. J.S., 2021;13.
- Ullah A, Aldakheel FM, Anjum SI, Raza G, Khan SA, Gajger IT. Pharmacological properties and therapeutic potential of honey bee venom. S.P.J. 2023; 31(1):96-109.
- Vega S, Abian O, Velazquez-Campoy A. On the link between conformational changes, ligand binding and heat capacity. BBA-General Subjects, 2016;5:868-878.
- Wang, C, Aleksandrov AA, Yang Z, Forouhar F, Proctor EA, Kota P et al. Ligand binding to a remote site thermodynamically corrects the F508del mutation in the human cystic fibrosis transmembrane conductance regulator. The Journal of biological chemistry, 2018;293:17685-17704.
- Wang, Z, Tan K. Honey Bee Alarm Pheromone Mediates Communication in Plant-Pollinator-Predator Interactions. Insects, 2019;10.
- Wehbe R, Frangieh J, Rima M, El Obeid D, Sabatier JM, Fajloun Z. Bee Venom: Overview of Main Compounds and Bioactivities for Therapeutic Interests. Molecules, 2019;24.
- Weis WA, Ripari N, Conte FL, da Silva-Honorio M, Sartori AA, Matucci RH et al. An overview about apitherapy and its clinical applications. J.P.P., 2022;2:100239.
- Wolber G, Langer T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J.o.c.i.m., 2005;45:160-169.
- Yassin MT, Mostafa AA, Al-Askar AA. Anticandidal and anti-carcinogenic activities of Mentha longifolia (Wild Mint) extracts in vitro. J.O.K.S.U.S., 2020;32: 2046-2052.
Arı Zehri Uçucu Maddelerini Keşfetmek: Kistik Fibrozis İçin Umut Veren Bir Çözüm
Yıl 2024,
, 267 - 284, 18.11.2024
Nilüfer Vural
,
Sibel Kaymak
,
Oğuz Yüce
Öz
Biyoaktif bileşiklerin karmaşık bir karışımı olan arı zehri, anti-inflamatuar, antimikrobiyal ve immünomodülatör özellikler göstermektedir. Özellikle arı zehri bileşenleri tarafından salınan uçucu bileşenler, solunum hastalıklarındaki potansiyelleri nedeniyle dikkat çekmektedir. Kistik fibroz (CF), CFTR proteinini etkileyen genetik bir mutasyonla karakterize, başta akciğerler ve sindirim sistemi olmak üzere çeşitli organlarda kalın ve yapışkan mukus üretimine yol açan ve yenilikçi tedavi yaklaşımları gerektiren zorlu bir hastalıktır. Bu araştırma, hem arı zehri uçucularının kimyasal bileşimini hem de CF hastalarında hava yolu inflamasyonu ve mukus viskozitesi üzerindeki etkilerini kimyasal ve in silico yöntemlerle araştırmıştır. Çeşitli SPME lifleri ile yapılan GC/MS analizleri, arı zehrinin uçucu bileşiklerinde 67 farklı bileşenin tanımlanmasını sağlamıştır. W/DVB, CAR-PDMS ve DVB-PDMS fiberleri için sırasıyla perilla alcohol (%42.21), tetradecane (%11.48) ve 1,2-benzenedicarboxylic acid, 1,2-bis(2-methylpropyl) ester (39.98) bileşenleri en yüksek miktarda belirlenmiştir. Daha sonra yapılan in silico analizler, bu bileşenlerin, temel sitokinleri modüle ederek ve CF hastalarının hava yollarındaki inflamatuar belirteçleri azaltarak anti-inflamatuar etkiler sergilediğini gösterdi. Bu araştırma, arı zehri uçucularının CF semptomlarını yönetmek için yeni bir terapötik yol olarak potansiyelini vurgulamaktadır. Arı zehrinin benzersiz özelliklerinden yararlanmak, kistik fibrozdan etkilenen bireylere yönelik hedefe yönelik tedavilerin geliştirilmesinde yeni bakış açıları sunabilir.
Kaynakça
- Abd El-Wahed AA, Farag MA, Eraqi WA, Mersal GAM, Zhao C, Khalifa SAM et al. Unravelling the beehive air volatiles profile as analysed via solid-phase microextraction (SPME) and chemometrics. Journal of King Saud University–Science, 2021;33:101449.
- Allen L, Carr SB, Davies G, Downey D, Egan M, Forton JT et al. Future therapies for cystic fibrosis. A.J.N.C., 2023;14:693.
- Barnes M, Brisbois EJ. Clinical use of inhaled nitric oxide: Local and systemic applications, J.F.R.B., 2020;152:422-431.
- Boch R, Shearer D, Stone BJN. Identification of iso-amyl acetate as an active component in the sting pheromone of the honey bee. Nature, 1962;195:1018-1020.
- Burley SK, Berman HM, Kleywegt GJ, Markley JL, Nakamura H., Velankar S. Protein Data Bank (PDB): the single global macromolecular structure archive. J.P.C.M., 2017;627-641.
- Camargos AF, Cossolin JFS, Martínez LC, Gonçalves WG, dos Santos MH, Zanuncio JC et al. Morphology and chemical composition of the Koschewnikow gland of the honey bee Apis mellifera (Hymenoptera: Apidae) workers engaged in different tasks. Journal of Apicultural Research, 2020;59:1037-1048.
- Castellani C, Assael BM. Cystic fibrosis: a clinical view. Cellular and molecular life sciences, 2017;74:129-140.
- Choi HS, Kang SY, Roh DH, Choi SR, Ryu Y, Lee JH. Bee venom stimulation of a lung meridian acupoint reduces inflammation in carrageenan-induced pleurisy: an alternative therapeutic approach for respiratory inflammation. .J.O.V.S.,2018;19:708-715.
- Cutting GR. Cystic fibrosis genetics: from molecular understanding to clinical application. J.N.R.G., 2015;16:45-56.
- Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. J.S.r., 2017;7:42717.
- de Graaf DC, Brochetto-Braga MR, de Abreu RMM, Blank S, Bridts CH., De Clerck LS et al. Standard methods for Apis mellifera venom research. Journal of Apicultural Research, 2021;60:1-31.
- de Lacy-Costello B, Amann A, Al-Kateb H, Flynn C, Filipiak W, Khalid T et al. A review of the volatiles from the healthy human body. J.O.B.R., 2014;8:014001.
- Dogru D, Çakır E, Şişmanlar T, Çobanoğlu N, Pekcan S, Çinel G et al. Cystic fibrosis in Turkey: First data from the national registry. J.P.P., 2020;55: 541-548.
- Fraser-Pitt D, O’Neil D. Cystic fibrosis–a multiorgan protein misfolding disease. Future science OA, 2015;1(2): DOI: 10.4155/fso.15.57.
- Fratellone PM, Tsimis F, Fratellone G. Apitherapy products for medicinal use.The Journal of Alternative and Complementary Medicine, 2016;22(12):1020-1022.
- Graeber SY, Mall MA. The future of cystic fibrosis treatment: from disease mechanisms to novel therapeutic approaches. J.T.L., 2023;402:1185-1198.
- Habryka C, Kruczek M, Drygaś B. Bee products used in apitherapy. J.W.S.N., 2016:254-258.
- Hasan A, Qazi JI, Tabssum F, Hussain A. Increased bee venom production in Apis mellifera workers on the provision of probiotics and organic acids. ISBAB, 2023;48.
- Isidorov V, Zalewski A, Zambrowski G, Swiecicka I. Chemical Composition and Antimicrobial Properties of Honey Bee Venom. Molecules, 2023;28:4135
- Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A et al. PubChem substance and compound databases J.N.a.r., 2016;44:1202-1213.
- Li J, Wang Z, Tan K, Qu Y, Nieh JC. Effects of natural and synthetic alarm pheromone and individual pheromone components on foraging behavior of the giant Asian honey bee, Apis dorsata. The Journal of experimental biology, 2014;217:3512-3518.
- Lillehoj EP, Kato K, Lu W, Kim KC. Cellular and molecular biology of airway mucins. J.I.R.O.C., 2013;(303):139-202.
- Matysiak J, Breborowicz A, Kycler Z, Derezinski P, Kokot ZJ. Immune and clinical response to honeybee venom in beekeepers. A.O.A., 2016;23.
- Maunz A, Gütlein M, Rautenberg M, Vorgrimmler D, Gebele D, Helma C. lazar: a modular predictive toxicology framework. Frontiers in pharmacology, 2013;4.
- Naehrig S, Chao CM, Naehrlich L. Cystic fibrosis: diagnosis and treatment. Deutsches Ärzteblatt International, 2017;114:33-34.
- Nakamura Y, Sugano A, Ohta M, Takaoka Y. Docking analysis and the possibility of prediction efficacy for an anti-IL-13 biopharmaceutical treatment with tralokinumab and lebrikizumab for bronchial asthma. J.P.O., 2017;12.
- Nikbakhtzadeh MR, Tirgari S, Fakoorziba MR, Alipour H. Two volatiles from the venom gland of the Samsum ant, Pachycondyla sennaarensis. Toxicon, 2009;54:80-82.
- Noël A, Dumas C, Rottier E, Beslay D, Costagliola G, Ginies C et al. Detailed chemical analysis of honey bee (Apis mellifera) worker brood volatile profile from egg to emergence. J.P.O., 2023;18.
- Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC et al. UCSF Chimera—a visualization system for exploratory research and analysis. J.O.C.C., 2004;25: 1605-1612.
- Samsuzzaman M, Uddin MS, Shah MA, Mathew B. Natural inhibitors on airway mucin: Molecular insight into the therapeutic potential targeting MUC5AC expression and production. J.L.s., 2019;231:116485.
- Schmitt T, Herzner G, Weckerle B, Schreier P, Strohm E. Volatiles of foraging honeybees Apis mellifera (Hymenoptera: Apidae) and their potential role as semiochemicals. J.A., 2007;38:164-170.
- Simone-Finstrom M, Angove M, Brooks P, Gerdts J. Identification and Discrimination of Volatiles Associated With Chalkbrood Infection in European Honey Bees (Apis mellifera), Eastern Australia. J.R.S., 2023;24.
- Stela M, Cichon N, Spławska A, Szyposzynska M, Bijak M. 2024. Therapeutic Potential and Mechanisms of Bee Venom Therapy: A Comprehensive Review of Apitoxin Applications and Safety Enhancement Strategies. Pharmaceuticals, 2024;17(9).
- Studio, Discovery studio. D.J.A., 2008.
- Topal E, Adamchuk L, Negri I, Kösoğlu M, Papa G, Dârjan MS et al. Traces of Honeybees, Api-Tourism and Beekeeping: From Past to Present. J.S., 2021;13.
- Ullah A, Aldakheel FM, Anjum SI, Raza G, Khan SA, Gajger IT. Pharmacological properties and therapeutic potential of honey bee venom. S.P.J. 2023; 31(1):96-109.
- Vega S, Abian O, Velazquez-Campoy A. On the link between conformational changes, ligand binding and heat capacity. BBA-General Subjects, 2016;5:868-878.
- Wang, C, Aleksandrov AA, Yang Z, Forouhar F, Proctor EA, Kota P et al. Ligand binding to a remote site thermodynamically corrects the F508del mutation in the human cystic fibrosis transmembrane conductance regulator. The Journal of biological chemistry, 2018;293:17685-17704.
- Wang, Z, Tan K. Honey Bee Alarm Pheromone Mediates Communication in Plant-Pollinator-Predator Interactions. Insects, 2019;10.
- Wehbe R, Frangieh J, Rima M, El Obeid D, Sabatier JM, Fajloun Z. Bee Venom: Overview of Main Compounds and Bioactivities for Therapeutic Interests. Molecules, 2019;24.
- Weis WA, Ripari N, Conte FL, da Silva-Honorio M, Sartori AA, Matucci RH et al. An overview about apitherapy and its clinical applications. J.P.P., 2022;2:100239.
- Wolber G, Langer T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J.o.c.i.m., 2005;45:160-169.
- Yassin MT, Mostafa AA, Al-Askar AA. Anticandidal and anti-carcinogenic activities of Mentha longifolia (Wild Mint) extracts in vitro. J.O.K.S.U.S., 2020;32: 2046-2052.