DOĞANIN ŞİFASI: ARI ZEHRİNİN SAĞLIK ÜZERİNDEKİ ETKİLERİ VE UYGULAMALARI

Year 2024, Volume: 24 Issue: 2, 387 - 403

Sibel Kaymak , Nilüfer Vural , Oğuz Yüce , Salih Mollahaliloğlu

https://doi.org/10.31467/uluaricilik.1512321

Abstract

Apiterapi, başta bal arısı zehri olmak üzere bal arısı ürünlerinin kullanımıyla yüzyıllardır birçok insanın şifa edindiği ve sıklıkla başvurulan bir integratif tedavi yöntemidir. Bal arısı zehri, insan vücuduna manuel enjeksiyonla topikal olarak veya doğrudan arı sokmasıyla uygulanabilmektedir. Bal arısı zehri içerdiği peptit ve enzimler sayesinde sahip olduğu yüksek biyoterapötik potansiyeli ile başta enflamatuvar hastalıklar olmak üzere nörodejeneratif hastalıklar ve romatoid artrit gibi kas-iskelet sistemi hastalıklarının tedavisinde kullanılmaktadır. Literatürdeki birçok çalışma, bal arısı zehri bileşenlerinin biyolojik aktivitelerini tanımlamış ve bu bileşenlerin yeni nesil ilaçlar olarak potansiyel kullanımını geliştirmek etrafında şekillenmiş durumdadır. Bu derlemenin amacı, bal arısı zehrinin toplanmasını, ana bileşenlerini, temel biyolojik özelliklerini ve terapötik uygulamalarını özetlemektir.

Keywords

Apiterapi, Bal arısı zehri, Apitoksin, Enflamasyon

Healing Power of Nature: Effects and Applications of Bee Venom on Health

Abstract

Apitherapy is an integrative treatment method that has been relied upon for centuries, using honeybee products, primarily bee venom, for healing many human ailments. Bee venom can be administered to the human body through manual injection, topically, or directly via bee stings. Bee venom contains various bioactive molecules such as peptides and enzymes, which possess significant biotherapeutic potential in treating inflammatory diseases, neurodegenerative disorders, and musculoskeletal conditions like rheumatoid arthritis. Numerous studies in the literature have identified the biological activities of bee venom components and have focused on developing the potential use of apitoxin and its constituents as next-generation drugs. The aim of this review is to summarize the collection of bee venom, its main components, fundamental biological properties, and therapeutic applications.

Keywords

Apitherapy, Bee venom, Apitoxin, Inflammation

References

• Aburayan WS, Alajmi AM, Alfahad AJ, Alsharif WK, Alshehri AA, Booq RY vd. Melittin from bee venom encapsulating electrospun fibers as a potential antimicrobial wound dressing patches for skin infections. J.P. 2022; 14(4): 725, doi.org/10.3390/pharmaceutics14040725.
• Ahmed O, Fahim H, Mahmoud A, Ahmed EAE. Bee venom and hesperidin effectively mitigate complete Freund’s adjuvant-induced arthritis via immunomodulation and enhancement of antioxidant defense system. JAR 2018; 33(2): 198, doi.org/10.5606/ArchRheumatol.2018.6519.
• Ahmedy OA, Ibrahim SM, Salem HH, Kandil EA. Antiulcerogenic effect of melittin via mitigating TLR4/TRAF6 mediated NF-κB and p38MAPK pathways in acetic acid-induced ulcerative colitis in mice. JCBI 2020;331: 109276, doi.org/10.1016/j.cbi.2020.109276.
• Alalawy AI, El Rabey HA, Almutairi FM, Tayel AA, Al-Duais MA, Zidan NS vd. Effectual anticancer potentiality of loaded bee venom onto fungal chitosan nanoparticles. I.j.o.p.s. 2020;(1): 2785304, doi.org/10.1155/2020/2785304.
• An HJ, Kim JY, Kim WH, Gwon MG, Gu HM, Jeon MJ vd. Therapeutic effects of bee venom and its major component, melittin, on atopic dermatitis in vivo and in vitro. B. j. o. p. 2018; 175(23): 4310-4324, doi.org/10.1111/bph.14487.
• Baracchi D. ve Turillazzi S. Differences in venom and cuticular peptides in individuals of Apis mellifera (Hymenoptera: Apidae) determined by MALDI-TOF MS. J. Insect Physiol. 2010;56(4):366-375, doi.org/10.1016/j.jinsphys.2009.11.013.
• Bidaud I, Chong ACY, Carcouet A, Waard SD, Charpentier F, Ronjat M vd. Inhibition of G protein-gated K+ channels by tertiapin-Q rescues sinus node dysfunction and atrioventricular conduction in mouse models of primary bradycardia. JSR 2020;10(1): 9835, doi.org/10.1038/s41598-020-66673-8.
• Bogdanov S. Bee venom: composition, health, medicine: a review. JP 2016;1-20.
• Boutrin MCF, Foster H, Pentreath VW. The effects of bee (Apis mellifera) venom phospholipase A2 on Trypanosoma brucei brucei and enterobacteria. J.E. p. 2008;119(2): 246-251, doi.org/10.1016/j.exppara.2008.02.002.
• Buhren BA, Schrumpf H, Hoff NP, Bölke E, Hilton S, Gerber PA. Hyaluronidase: from clinical applications to molecular and cellular mechanisms. E. j. o. m. r. 2016; 21: 1-7, doi.org/10.1186/s40001-016-0201-5.
• Cai M, Choi SM, Yang EJ. The effects of bee venom acupuncture on the central nervous system and muscle in an animal hSOD1G93A mutant. EJJT 2015;7(3): 846-858, doi.org/10.3390/toxins7030846.
• Carpena M, Nuñez-Estevez B, Soria-Lopez A, Simal-Gandara J. Bee venom: an updating review of its bioactive molecules and its health applications. J.N. 2020;12(11): 3360, doi.org/10.3390/nu12113360.
• Carreck NL. Fifty years of the Journal of Apicultural Research. J.o.A.R. 2011; 50(4): 249-256, doi.org/10.3896/IBRA.1.50.4.01.
• Cho SY, Shim SR, Rhee HY, Park HJ, Jung WS, Moon SK, Park JM vd. Effectiveness of acupuncture and bee venom acupuncture in idiopathic Parkinson's disease. Parkinsonism & Related Disorder. 2012;18(8): 948-952, doi.org/10.1016/j.parkreldis.2012.04.030.
• Cohen BE, Bashey S, Wysong A. The use of hyaluronidase in cosmetic dermatology: a review of the literature. J.C.I.D. 2015;3(2): 7.
• Cornara L, Biagi M, Xiao J, Burlando B. Therapeutic properties of bioactive compounds from different honeybee products. Front. Pharmacol. 2017;8: 261216, doi.org/10.3389/fphar.2017.00412.
• Dacheux M, Sinou V, Payré C, Jeammet L, Parzy D, Grellier P vd. Antimalarial activity of human group IIA secreted phospholipase A2 in relation to enzymatic hydrolysis of oxidized lipoproteins. J.I.I. 2019; 87(11), doi.org/10.1128/iai.00556-19.
• de Graaf DC, Braga MRB, de Abreu RMM, Blank S, Bridts CH, De Clerck LS vd. Standard methods for Apis mellifera venom research. J.A.R. 2021;60(4): 1-31, doi.org/10.1080/00218839.2020.1801073.
• de Matos Silva LFC, Ramos ERP, Ambiel CR, Correia-de-Sá P, Alves-Do-Prado W. Apamin reduces neuromuscular transmission by activating inhibitory muscarinic M2 receptors on motor nerve terminals. E.j.o.p. 2010;626(2-3): 239-243, doi.org/10.1016/j.ejphar.2009.09.064.
• Doo AR, Kim ST, Kim SN, Moon W, Yin CS, Chae Y vd. Neuroprotective effects of bee venom pharmaceutical acupuncture in acute 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced mouse model of Parkinson's disease. Neurol. Res. 2010;32(sup1): 88-91, doi.org/10.1179/016164109X12537002794282.
• dos Santos-Pinto JRA, Perez-Riverol A, Lasa AM, Palma MS. Diversity of peptidic and proteinaceous toxins from social Hymenoptera venoms. J.T. 2018;148: 172-196, https://doi.org/10.1016/j.toxicon.2018.04.029.
• Drici MD, Diochot S, Terrenoire C, Romey G, Lazdunski MJ. The bee venom peptide tertiapin underlines the role of IKACh in acetylcholine‐induced atrioventricular blocks. B.j.o.p. 2009;131(3): 569-577, https://doi.org/10.1038/sj.bjp.0703611.
• El-Hanoun A, El-Komy A, El-Sabrou K, Abdella M. Effect of bee venom on reproductive performance and immune response of male rabbits. Physiol. Behav. 2020;223: 112987, doi.org/10.1016/j.physbeh.2020.112987.
• Elieh AK, Shafaghat DF, Zwiener RD. Immunology of bee venom. Clin. Rev. Allergy Immunol. 2018;54: 386-396, doi.org/10.1007/s12016-017-8597-4.
• Gaudenzio N, Sibilano R, Marichal T, Starkl P, Reber LL, Cenac N vd. Different activation signals induce distinct mast cell degranulation strategies. JCI 2016;126(10): 3981-3998, doi.org/10.1172/JCI85538.
• Gauldie J, Hanson JM, Rumjanek FD, Shipolini RA, Vernon CA. The peptide components of bee venom. Eur. J. Biochem. 1976;61(2): 369-376, doi.org/10.1111/j.1432-1033.1976.tb10030.x.
• Georgieva D, Greunke K, Genov N, Betzel C. 3-D Model of the bee venom acid phosphatase: Insights into allergenicity. BBRC 2009;378(4): 711-715, doi.org/10.1016/j.bbrc.2008.11.101.
• Gokulakrishnaa R,Thirunavukkarasu S. Apitherapy: A valuable gift from honey bee. J. Entomol. Zool. Stud. 2020;8(5): 2317-2323.
• Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W. Amyotrophic lateral sclerosis. Nat. Rev. Dis. Primers 2017;3(1): 1-19, doi.org/10.1038/nrdp.2017.71.
• Hood JL, Jallouk AP, Campbell N, Ratner L, Wickline SA. Cytolytic nanoparticles attenuate HIV-1 infectivity. Antivir. Ther. 2013;18(1): 95-103, doi.org/10.3851/IMP2346.
• Huh JE, Baek YH, Lee MH, Choi DY, Park DS, Lee JD. Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice. Cancer letters 2010;292(1): 98-110, doi.org/10.1016/j.canlet.2009.11.013.
• Hwang JH. Bee Venom Acupuncture Induced Skin Patch Discoloration Persisting for More Than 3 Years: A Case Report. Chinese Journal of Integrative Medicine 2021;27(10): 774-777, doi.org/10.1007/s11655-021-3496-1.
• Jin W, Lu Z. Synthesis of a stable form of tertiapin: a high-affinity inhibitor for inward-rectifier K+ channels. J.B. 1999;38(43): 14286-14293, doi.org/10.1021/bi991205r.
• Isidorov V, Zalewski A, Zambrowski G, Swiecicka I. Chemical composition and antimicrobial properties of honey bee venom. Molecules 2023;28(10):4135, doi.org/10.3390/molecules28104135.
• Jo M, Park MH, Kollipara PS, An BJ, Song HS, Han SB vd. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. J.T. 2012;258(1): 72-81, doi.org/10.1016/j.taap.2011.10.009.
• Kanjhan R, Coulson EJ, Adams DJ, Bellingham MC. Tertiapin-Q blocks recombinant and native large conductance K+ channels in a use-dependent manner. J.J.o.P. 2005;314(3): 1353-1361, doi.org/10.1124/jpet.105.085928.
• Kim BY, Lee KS, Ok M, Jin BR. Synthetic secapin bee venom peptide exerts an anti-microbial effect but not a cytotoxic or inflammatory response. J. Asia. Pac. Entomol. 2017;20(1): 151-155, doi.org/10.1016/j.aspen.2016.12.009.
• Kim CM. Biotherapy-History, Principles and Practice, “Apitherapy–bee venom therapy” Springer, Netherlands, 2013, p.77-112.
• Kim DH, Sin DC, Song HS. Current status of intervention studies on Acupuncture for Parkinson’s disease. JAR 2017; 34(3): 13-21, doi.org/10.13045/acupunct.2017089.
• Kim JI, Yang EJ, Lee MS, Kim YS, Huh Y, Cho IH vd. Bee venom reduces neuroinflammation in the MPTP-induced model of Parkinson's disease. Int.J.Neurosci. 2011; 121(4): 209-217, doi.org/10.3109/00207454.2010.548613.
• Kim JY, Leem J, Park KK. Antioxidative, antiapoptotic, and anti-inflammatory effects of apamin in a murine model of lipopolysaccharide-induced acute kidney injury. J.M. 2020;25(23): 5717, doi.org/10.3390/molecules25235717.
• Kim WH, An HJ, Kim JY, Gwon MG, Gu H, Lee SJ vd. Apamin inhibits TNF-α-and IFN-γ-induced inflammatory cytokines and chemokines via suppressions of NF-κB signaling pathway and STAT in human keratinocytes JPR 2017;69(5): 1030-1035, doi.org/10.1016/j.pharep.2017.04.006.
• Klocek G, Schulthess T, Shai Y, Seelig J. Thermodynamics of melittin binding to lipid bilayers: Aggregation and pore formation J.B. 2009;48(12): 2586-2596, doi.org/10.1021/bi802127h.
• Koburova KL, Michailova SG, Shkenderov SV. Further investigation on the antiinflammatory properties of adolapin-bee venom polypeptide. Acta Physiol. Pharmacol. Bulg. 1985; 11(2): 50-55.
• Kocyigit A, Guler EM, Kaleli S. Anti-inflammatory and antioxidative properties of honey bee venom on Freund's Complete Adjuvant-induced arthritis model in rats. J.T. 2019;161: 4-11, doi.org/10.1016/j.toxicon.2019.02.016.
• Kolaylı S. Bal arisi zehrinin karakterizasyonunda sds-page elektroforez kullanilabilirliğinin araştirilmasi. Uludağ Arıcılık Dergisi, 2017;16(2):49-56, doi.org/10.31467/uluaricilik.379483.
• Kong GM, Tao WH, Diao YL, Fang PH, Wang JJ, Bo P vd. Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway. WJG 2016;22(11): 3186, doi.org/10.3748/wjg.v22.i11.3186.
• Kritsky G. Beekeeping from Antiquity Through the Middle Ages. Annu. Rev. Entomol. 2017;62: 249-264, doi.org/10.1146/annurev-ento-031616-035115.
• Kuzmenkov AI, Peigneur S, Nasburg JA, Mineev KS, Nikolaev MV, Pinheiro-Junior EL vd. Apamin structure and pharmacology revisited. Front. Pharmacol. 2022;13: 977440, doi.org/10.3389/fphar.2022.977440.
• Kwon NY, Sung SH, Sung HK, Park JK. Anticancer activity of bee venom components against breast cancer. J.T. 2022;14(7): 460, doi.org/10.3390/toxins14070460.
• Kwon YB, Lee JD, Lee HJ, Han HJ, Mar WC, Kang SK vd. Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses. J.P. 2001;90(3): 271-280, doi.org/10.1016/S0304-3959(00)00412-7.
• Lee C., Bae SJS, Joo H, Bae H. Melittin suppresses tumor progression by regulating tumor-associated macrophages in a Lewis lung carcinoma mouse model. J.O. 2017;8(33): 54951, doi.org/10.18632/oncotarget.18627.
• Lee G., Bae H. Anti-inflammatory applications of melittin, a major component of bee venom: Detailed mechanism of action and adverse effects J.M. 2016;21(5): 616, doi.org/10.3390/molecules21050616.
• Lee G., Bae H. Bee venom phospholipase A2: Yesterday’s enemy becomes today’s friend. J. T. 2016;8(2): 48, doi.org/10.3390/toxins8020048.
• Lee J, Kim YM, Kim JH, Cho CW, Jeon JW, Park JK vd. Nasal delivery of chitosan/alginate nanoparticle encapsulated bee (Apis mellifera) venom promotes antibody production and viral clearance during porcine reproductive and respiratory syndrome virus infection by modulating T cell related responses. Vet. Immunol. Immunopathol. 2018;200: 40-51, doi.org/10.1016/j.vetimm.2018.04.006.
• Lee MT, Sun TL, Hung WC, Huang HW. Process of inducing pores in membranes by melittin. PNAS 2013;110(35): 14243-14248, doi.org/10.1073/pnas.1307010110.
• Lee SH, Choi SM, Yang EJ. Melittin ameliorates the inflammation of organs in an amyotrophic lateral sclerosis animal model. Exp. Neurobiol. 2014;23(1): 86, doi.org/10.5607/en.2014.23.1.86.
• Lee WR, Kim KH, An HJ, Kim JY, Chang YC, Chung H vd. The protective effects of Melittin on Propionibacterium acnes–induced inflammatory responses in vitro and in vivo. J. Invest. Dermatol. 2014;134(7): 1922-1930, doi.org/10.1038/jid.2014.75.
• Lee YM, Cho SN, Son E, Song CH, Kim DS. Apamin from bee venom suppresses inflammation in a murine model of gouty arthritis. J. Ethnopharmacol. 2020;257: 112860, doi.org/10.1016/j.jep.2020.112860.
• Lim HN, Baek SB, Jung HJ Bee venom and its peptide component melittin suppress growth and migration of melanoma cells via inhibition of PI3K/AKT/mTOR and MAPK pathways. J.M. 2019;24(5): 929, doi.org/10.3390/molecules24050929.
• Lin TY, Hsieh CL. Clinical applications of bee venom acupoint injection. J.T. 2020; 12(10): 618, doi.org/10.3390/toxins12100618.
• Liu J, Xiao S, Li J, Yuan B, Yang K, Ma Y. Molecular details on the intermediate states of melittin action on a cell membrane. BBA 2018;1860(11): 2234-2241, doi.org/10.1016/j.bbamem.2018.09.007.
• Małek A, Strzemski M, Kurzepa J, Kurzepa J. Can bee venom be used as anticancer agent in modern medicine? J.C. 2023;15(14): 3714, doi.org/10.3390/cancers15143714.
• Markovic O, Molnar L. Isolation and determination of honey bee poison. Chemicke Zvesti 1954;8:80-98
• Memariani H, Memariani M, Moravvej H, Shahidi-Dadras M. Melittin: a venom-derived peptide with promising anti-viral properties. J.E.J.o.C. 2020;39(1): 5-17, doi.org/10.1007/s10096-019-03674-0.
• Meng Y, Yang XX, Sheng YX, Zhang JL. A novel peptide from Apis mellifera and solid-phase synthesis of its analogue. J.C.C.L. 2012;23(10): 1161-1164, doi.org/10.1016/j.cclet.2012.09.003.
• Mohamed WA, Abd-Elhakim YM, Ismail SA Involvement of the anti-inflammatory, anti-apoptotic, and anti-secretory activity of bee venom in its therapeutic effects on acetylsalicylic acid-induced gastric ulceration in rats. J.T. 2019; 419: 11-23, doi.org/10.1016/j.tox.2019.03.003.
• Mohammadi-Rad M, Ghasemi N, Aliomrani M. Evaluation of apamin effects on myelination process in C57BL/6 mice model of multiple sclerosis. Res Pharm Sci. 2019;14(5): 424-431, doi.org/10.4103/1735-5362.268203.
• Moreno M, Giralt E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan. J.T. 2015; 7(4): 1126-1150, doi.org/10.3390/toxins7041126.
• Moridi K, Hemmaty M, Eidgahi MRA, Najafi MF, Zare H, Ghazvini K, Neshani A. Construction, cloning, and expression of Melittin antimicrobial peptide using Pichia pastoris expression system. J.G.R. 2020;21: 100900, doi.org/10.1016/j.genrep.2020.100900.
• Mourelle D, Brigatte P, Bringanti LDB, De Souza BM, Arcuri HA, Gomes PC vd. Hyperalgesic and edematogenic effects of Secapin-2, a peptide isolated from Africanized honeybee (Apis mellifera) venom. J.P. 2014;59: 42-52, doi.org/10.1016/j.peptides.2014.07.004.
• Nevalainen TJ, Graham GG, Scott KF. Antibacterial actions of secreted phospholipases A2.Review. B.B.A. 2008;1781(1-2): 1-9, doi.org/10.1016/j.bbalip.2007.12.001.
• Ong WY, Farooqui T, Farooqui A. Involvement of cytosolic phospholipase A2, calcium independent phospholipase A2 and plasmalogen selective phospholipase A2 in neurodegenerative and neuropsychiatric conditions. Curr. Med. Chem. 2010;17(25): 2746-2763, doi.org/10.2174/092986710791859289.
• Palma MS. Hymenoptera insect peptides. J. H.o.b.a.p. 2013;416-422, doi.org/10.1016/B978-012369442-3/50059-3.
• Palmer D. Extraction of bee venom for research J.B.W. 1961;42(9): 225-226.
• Park MH, Choi MS, Kwak DH, Oh KW, Yoon DY, Han SB vd. Anti‐cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF‐Κb. J.T.P. 2011;71(8): 801-812, doi.org/10.1002/pros.21296.
• Peiren N, Vanrobaeys F, de Graaf DC, Devreese B, Van B, Jacobs FJ. The protein composition of honeybee venom reconsidered by a proteomic approach. J.P.P. 2005;1752(1): 1-5, doi.org/10.1016/j.bbapap.2005.07.017.
• Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC vd. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 2004;25:1605-1612, doi.org/10.1002/jcc.20084.
• Picoli T, Peter CM, Vargas GD, Hübner SO, Lima MD, Fischer G. Antiviral and virucidal potential of melittin and apamin against bovine herpesvirus type 1 and bovine viral diarrhea virus. J.P.V.B. 2018;38: 595-604, doi.org/10.1590/1678-5150-PVB-4758.
• Premrajan P, Jayanandan A, Variyar EJ. PLA2: Implications in neurological disorders as a prospective therapeutic target. Phospholipases in Physiology and Pathology, Elsevier 2023;139-158, doi.org/10.1016/B978-0-323-95696-3.00001-6.
• Pucca MB, Cerni FA, Oliveira IS, Jenkins TP, Argemí L, Sørensen CV vd. Bee updated: current knowledge on bee venom and bee envenoming therapy. Front. Immunol. 2019;10:2090, doi.org/10.3389/fimmu.2019.02090.
• Putz T, Ramoner R, Gander H, Rahm A, Bartsch G, Bernardo K vd. Bee venom secretory phospholipase A2 and phosphatidylinositol-homologues cooperatively disrupt membrane integrity, abrogate signal transduction and inhibit proliferation of renal cancer cells. Cancer Immunol. Immunother. 2007;56: 627-640, doi.org/10.1007/s00262-006-0220-0.
• Qiao M, Chen D, Hao T, Zhao X, Hu H, Ma X. Effect of bee venom peptide–copolymer interactions on thermosensitive hydrogel delivery systems. Int. J. Pharm. 2007;345(1-2): 116-124, doi.org/10.1016/j.ijpharm.2007.05.056.
• Radu AF, Bungau SG. Management of rheumatoid arthritis: an overview. J.C. 2021;10(11): 2857, doi.org/10.3390/cells10112857.
• Ransome HM. “The sacred bee in ancient times and folklore” Courier Corporation, 2004 Samancı T. ve Kekeçoğlu M. Comparison of commercial and anatolian bee venom in terms of chemical composition. Uludağ Arıcılık Dergisi, 2019;19(1):61-68, doi.org/10.31467/uluaricilik.527986.
• Shi W, Li C, Li M, Zong X, Han D, Chen Y. Antimicrobial peptide melittin against Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen in rice. J.A.M.B. 2016;100: 5059-5067, doi.org/10.1007/s00253-016-7400-4.
• Shipman WH, Cole LJ. A surfactant bee venom fraction: separation on a newly devised constant flow rate chromatographic column and detection by changes in effluent drop volume. J.A.B. 1969; 29(3): 490-497, doi.org/10.1016/0003-2697(69)90333-9.
• Shkenderov S, Koburova K. Adolapin - A newly isolated analgetic and anti-inflammatory polypeptide from bee venom J.T. 1982;20(1): 317-321, doi.org/10.1016/0041-0101(82)90234-3.
• Sobral F, Sampaio A, Falcão S, Queiroz MJR, Calhelha RC, Vilas-Boas M vd. Chemical characterization, antioxidant, anti-inflammatory and cytotoxic properties of bee venom collected in Northeast Portugal. J.F.C.T. 2016;94: 172-177, doi.org/10.1016/j.fct.2016.06.008.
• Soliman C, Eastwood S, Truong VK, Ramsland PA, Elbourne A. The membrane effects of melittin on gastric and colorectal cancer J.P.O. 2019;14(10): e0224028, doi.org/10.1371/journal.pone.0224028.
• Somwongin S, Chantawannakul P, Chaiyana W. Antioxidant activity and irritation property of venoms from Apis species. J.T. 2018;145: 32-39, doi.org/10.1016/j.toxicon.2018.02.049.
• Touchard A, Téné N, Song PCT, Lefranc B, Leprince J, Treilhou M vd. Deciphering the molecular diversity of an ant venom peptidome through a venomics approach J.P.R. 2018;17(10): 3503-3516, doi.org/10.1021/acs.jproteome.8b00452.
• Uddin MB, Lee BH, Nikapitiya C, Kim JH, Kim TH, Lee HC vd. Inhibitory effects of bee venom and its components against viruses in vitro and in vivo. J.M. 2016; 54: 853-866, doi.org/10.1007/s12275-016-6376-1.
• 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, doi.org/10.1016/j.jsps.2022.11.008.
• Uzuner, SÇ, Birinci E, Tetikoğlu S, Birinci C, Kolaylı S. Distinct Epigenetic Reprogramming, Mitochondrial Patterns, Cellular Morphology, and Cytotoxicity after Bee Venom Treatment. Recent Pat. Anticancer Drug Discov. 2021;16(3):377–392, doi.org/10.2174/1574892816666210422125058.
• Van-Vaerenbergh M, Debyser G, Devreese B, de Graaf DCJ Exploring the hidden honeybee (Apis mellifera) venom proteome by integrating a combinatorial peptide ligand library approach with FTMS. J.P. 2014;99: 169-178, doi.org/10.1016/j.jprot.2013.04.039.
• Wieser W. “Effects of temperature on ectothermic organisms” Springer, 1973
• Xing L, Dawei C, Liping X, Rongqing ZJ Oral colon-specific drug delivery for bee venom peptide: development of a coated calcium alginate gel beads-entrapped liposome. J.C.R. 2003; 93(3): 293-300, doi.org/10.1016/j.jconrel.2003.08.019.
• Yang EJ, Choi SM. α‐Synuclein modification in an ALS animal model. J.E.B.C. 2013(1); 259381, doi.org/10.1155/2013/259381.
• Ye X, Guan S, Liu J, Ng CWW, Chan HH, Sze SCW vd. Activities of venom proteins and peptides with possible therapeutic applications from bees and WASPS. J.H.J.P. 2016;23(8): 748-755, doi.org/10.2174/0929866523666160618120824.
• Yu X, Chen L, Liu J, Dai B, Xu G, Shen G vd. Immune modulation of liver sinusoidal endothelial cells by melittin nanoparticles suppresses liver metastasis. J.N.C. 2019;10(1): 574, doi.org/10.1038/s41467-019-08538-x.