Hornet, wasp and bee toxin peptides: biological activity, pharmaceutical and therapeutic uses

Hornet, wasp and bee toxin peptides

  • Ravi Kant Upadhyay
  • SIMRAN SHARMA Department of Zoology, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur

Abstract

The present review article explains the salient features of hornet venom toxins, their physiological, biological and pharmacological effect on animals and man. Hornets sting very fast and inflict venom which is more dangerous than those of bees. Hornet venom contains both proteinaceous and non-proteinaceous peptides i.e. scapin, adolapin, melitin, mastoparans and enzymes mainly phospholipase and hyaluronidase which show multiple biological effects i.e. cytolytic, hemotoxic, neuro-inhibitor, anticancer, anti-parasitic, immune hypersensitive, inflammatory, antimicrobial and anti-insect activities. Hornet stings are more painful to humans than typical wasp stings because hornet venom contains a large amount (5%) of acetylcholine. Hornet toxin components interact with receptors, ion channels and gated channels and affect permeability functions of cells. Heavy envenomation shows impose quick patho-physiological lethal effects in man and pet. This article emphasizes the use of various hornet venom components for production of disease-modifying anti-rheumatic and analgesic, anticancer drugs and insecticides. Hornet venom allergens could be used to prepare the rational design of component-resolved diagnosis of allergy and venom immunotherapy of inflicting patients.

Keywords: Hornets stings, venom and toxin anticancer activity, anti-parasitic, immune hypersensitivity activities.

Downloads

Download data is not yet available.

References

1. Warrell DA. Venomous Bites, Stings, and Poisoning: An Update. Infect Dis Clin North Am. 2019;33:17-38.

2. Archer, METaxonomy of the sylvestris group (Hymenoptera: Vespidae, Dolichosvespula) with the introduction of a new name and notes on distribution. Entomological Scandinavica,1981;12:187–193.
3. Dos Santos-Pinto JRA, Perez-Riverol A, Lasa AM, Palma MS. Diversity of peptidic and proteinaceous toxins from social Hymenoptera venoms.Toxicon. 2018;148:172-196.

4. Pessoa, WFB, Silva, LCC, De Oliveira Dias, L. Delabie, et al C.C. Analysis of Protein Composition and Bioactivity of Neoponeravillosa Venom (Hymenoptera: Formicidae. Int. J. Mol. Sci. 2016;17:513.

5. Liu Z, Chen S, Zhou Y, Xie C, Zhu B, Zhu H, Liu S, et al. Deciphering the venomictranscriptome of killer-wasp Vespa velutina.Sci Rep. 2015 ;5:94-54.

6. Kularatne K , Kannangare T, Jayasena A, Jayasekera A, Waduge R, Weerakoon K, KularatneSA. Fatal acute pulmonary oedema and acute renal failure following multiple wasp/hornet (Vespa affinis) stings in Sri Lanka: two case reports.J Med Case Rep. 2014;8:188

7. Baptista-Saidemberg NB, Saidemberg DM, Palma MS. Profiling the peptidome of the venom from the social waspAgelaiapallipespallipes.J Proteomics. 2011;74:2123-37.


8. Brigatte P, Cury Y, de Souza BM, Baptista-Saidemberg NB, Saidemberg DM, Gutierrez VP, et al. Hyperalgesic and edematogenic effects of peptides isolated from the venoms of honeybee (Apismellifera) and neotropical social wasps (Polybiapaulista and Protonectarinasylveirae).Amino Acids.2011 ;40:101-11.

9. Diaz JH. The evolving global epidemiology, syndromic classification, management, and prevention of caterpillar envenoming. Am J Trop Med Hyg. 2005;72:347-57.

10. Petricevich VL 2004. Cytokine and nitric oxide production following severe envenomation.Curr Drug Targets Inflamm Allergy. 2004;3:325-32.

11. Huicab-Uribe MA, Verdel-Aranda K, Martínez-Hernández A, Zamudio FZ, Jiménez-Vargas JM, Lara-Reyna J. Molecular composition of the paralyzing venom of three solitary wasps (Hymenoptera: Pompilidae) collected in southeast Mexico.Toxicon.2019;168:98-102 .

12. Alvarado G, Holland SR, DePerez-Rasmussen J, Jarvis BA, Telander T, Wagner N, et al. Bioinformatic analysis suggests potential mechanisms underlying parasitoid venom evolution and function.Genomics.2019;112;1096-1104.
13. Elias LG, Silva DB, Silva R, Peng YQ, Yang DR, Lopes NP, et al. A comparative venomic fingerprinting approach reveals that galling and non-galling fig wasp species have different venom profiles. PLoS One. 2018;13:e0207051.

14. Catania KC. How Not to Be Turned into a Zombie.CataniaKC.BrainBehavEvol. 2018;92:32-46.

15. Hider RC, Ragnarsson U. A comparative structural study of apamin and related bee venom peptides. BiochimBiophysActa. 1981;667:197-208.

16. Edstrom A. Venomous and poisonous animals, Krieger Publishing Company, Malabar. 1992,210.

17. Hoffman DR. Hymenoptera venom proteins, J. Nat. Toxins1996;2:169-86.

18. Lima P RM, Brochetto-Braga MR, Chaud-Neto J. Proteolytic activity of Africanized honeybee(Apismellifera: hymenoptera, Apidae) venom, J. Venom. Anim. Toxins 2000;6: 64-76.
19. Haim B, Rimon A, Ishay JS, Rimon S. Purification, characterization and anticoagulant activit of a proteolytic enzyme from Vespa orientalisvenom, Toxicon1999;37:825-829.
20. Schmidt JO. Venoms of the hymenoptera, Piek T ed., Academic Press, London, 1986, 425-508
21. Sousa JRF, Monteiro RQ, Castro HC, Zingali RB. Proteolytic action of Bothropsjararacavenom upon its own constituents, Toxicon 2001;39:787-792.
22. Hoffman DR, Jacobson RS. Allergens in hymenoptera venom XXVII: bumblebee venom allergy and allergens, J. Allergy Clin. Immunol 1996;97:812-821.
23. Koh Y, Chung K, Kim D. Biochemical characterization of a thrombin-like enzyme and a fibrinolyticserine protease from snake (Agkistrodonsaxatilis) venom, Toxicon 2001;39: 555-560.
24. Michelutti KB, Antonialli-Junior WF, Batistote M, Cardoso CA.Chemical signatures in the developmental stages of exigua.GenetMol Res. 2016 28;15..
25. Ho CL, Ko JL. Hornetin: The lethal protein of the hornet (Vespa havitrsus) venom, FEBS Lett.,1986;209:18-22.
26. Humblet Y, Sonnet J, Van Y, Persele de Strihou C. Bee sting and acute tubular necrosis, Nephron 1982;31:187-188.
27. Schumacher MJ, Schmidt JO, Egen NB, Lowry JE. Quantity, analysis, and lethality of European-and Africanized honey bee venoms, Am. J. Trop. Med. Hyg1990;3:79-86.
28. Youloten LJF, Atkinson BA, Lee TH. The incidence and nature of adverse reactions to injection immunotherapy in bee and wasp venom allergy”, Clinical and Experimental Allergy1995;25:159-165.
29. Sherman R. What physicians should know about Africanized honeybees. West. J. Med 1995;163:541-546.
30. Schmidt JO. Toxicology of venoms from the honeybee genus Apis, Toxicon 1995;33:917-927.
31. Golden DB. Insect sting allergy and venom immunotherapy, Ann. Allergy Asthma Immunol 2006;96: 16-21.
32. Sasvary T, Mueller U. Deaths from insect stings in Switzerland 1978-1987:,SchweizerischeMedizinischeWochenschrifit 1994;124:1887-1894.
33. Jones RG, Corteling RL, Bhogal G, Landon J. A novel Fab-based anti-venom for the treatment of mass bee attacks, Am. J. Trop. Med. Hyg 1999;61:361-366.
34. Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY. IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol. 1998;160:3555-61.

35. Paull BR, Jacob G L, Yunginger JW, Gleich GJ. Comparison of binding of IgE and IgG antibodies to honeybee venom phospholipase A, J. Immunol., 1978;120:1917-1923.

36. Kemeny DM, Dalton N, Lawrence AJ, Pearce FL, Vernon CA. The purification and characterisation of hyaluronidase from the venom of the honey bee, Apismellifera. Eur J Biochem. 1984;139:217-23.

37. Neuman W, Habermann E, Amend G, Banks BEC, Shipolini RA. Venoms of hymenoptera: Biochemical, pharmacological and behavioral aspects, Peak T ed., Academy Press, London 1986;329-416.

38. Schumacher MJ, Schmidt JO, Egen NB, Lowry JE. Quantity, analysis, and lethality of European and Africanized honey bee venoms, Am. J. Trop. Med. Hyg, 1990;43:79-86.


39. Habermann E.Bee and Wasp venoms, Science 1972;177:314-322.

40. Winston ML. The Africanized “killer” bee: biology and public health, Q. J. Med 1994;84.


41. Kolecki P. Delayed toxic reaction following massive bee envenomation, Ann. Emerg. Med1999;114-116.

42. Hossen, MS, Shapla, UM, Gan, SH, Khalil, MI. Impact of Bee Venom Enzymes on Diseases and Immune Responses. Molecules 2017;22-25.

43. Welton RE, Williams DJ, Liew D. Injury trends from envenoming in Australia, 2000 2013.Intern Med J. 2017;47:170-176.

44. Liu X, Chen D, Xie L, Zhang R. Effect of honeybee venom on proliferation of K1735M2 mouse melanoma cells in vitro and growth of murine B16 melanomas in-vitro, J Pharm Pharmacol 2002;54:1083-1089.

45. Kularatne SA, Raveendran S, Edirisinghe J, Karunaratne I, WeerakoonK.First Reported Case of Fatal Stinging by the Large Carpenter Bee Xylocopatranquebarica.Wilderness Environ Med. 2016 ;27:2625.

46. Kannangare T, GluN2A-/- Mice Lack Bidirectional Synaptic Plasticity in the Dentate Gyrus and Perform Poorly on Spatial Pattern Separation Tasks.Cereb Cortex 2015, 25:2102-13.

47. Dos santos JA, DE Azevedo Duarte L, Otero IV production of laccase, manganese peroxidase and lignin peroxidase by Brazilian marine derived fungi.Enzymemicrobtechnol 2010;46:32-37.
48. Perez-Riverol A, Dos Santos-Pinto JRA, Lasa AM, Palma MS, Brochetto-Braga MR.J Proteomics 2017;161:88-103.

49. Orsolic N. Bee venom in cancer therapy. Cancer Metastasis Rev. 2012;31:173–194.

50. Hackethal A, Schmidt K. Bee venom therapy, bee venom acupuncture of apiculture: What is the evidence behind the various health claims? Am. Bee J. 2005;145:665–668.


51. Lee WR, Pak SC, Park KK. The protective effect of bee venom on fibrosis causing inflammatory diseases. Toxins (Basel). 2015;7:4758-72.

52. Heinen , TE and ABGorini da Veiga, 2011. Arthropoda venoms and cancer , Toxicon 57;497-511
53. Kachel HS, Buckingham SD, Sattelle DB. Insect toxins -selective pharmacological tools and drug/chemical leads. CurrOpin Insect Sci. 2018;30:93-98.

54. Lee JA, Son MJ, Choi J, Jun JH, Kim JI, Lee MS. Bee venom acupuncture for rheumatoid arthritis: A systematic review of randomised clinical trials. BMJ Open. 2014;4:e006140..

55. Seo BK, Lee JH, Sung WS, Song EM, Jo DJ. Bee venom acupuncture for the treatment of chronic low back pain: Study protocol for a randomized, double-blinded, sham-controlled trial. Trials. 2013;14:16.
56. Seo BK, Lee JH, Kim PK, Baek YH, Jo DJ, Lee S. Bee venom acupuncture, NSAIDs or combined treatment for chronic neck pain: Study protocol for a randomized, assessor-blind trial. Trials. 2014;15:132.
57. Rueff F, Mosbech H, Bonifazi F, Oude-Elberink J.N.G., EAACI Interest Group on Insect Venom Hypersensitivity Diagnosis of Hymenoptera venom allergy. Allergy. 2005;60:1339–1349.
58. Raghuraman H, Chattopadhyay A. Melittin: A membrane-active peptide with diverse functions. Biosci. Rep. 2007;27:189–223.
59. Damianoglou a, Rodger A, Pridmore C, Dafforn TR, Mosely JA, Sanderson JM, Hicks MR. The synergistic action of melittin and phospholipase A2 with lipid membranes: Development of linear dichroism for membrane-insertion kinetics. Protein Pept.Lett. 2010;17:1351–1362.
60. Vila-Farres X. Giralt E., Vila J. Update of peptides with antibacterial activity. Curr. Med. Chem. 2012;19:6188–6198.
61. Blondelle SE, Houghten RA. Hemolytic and antimicrobial activities of the twenty-four individual omission analogues of melittin. Biochemistry. 1991;30:4671–4678.
62. Dempsey CE. The actions of melittin on membranes. Biochim.Biophys.Acta. 1990;1031:143–161.
63. BomanHG,Wade D, Boman IA, Wahlin B, Merrifield RB. Antibacterial and antimalarial properties of peptides that are cecropin-melittin hybrids. FEBS Lett. 1989;259:103–106.
64. Merrifield RB. JuvvadiP, Andreu D, Ubach J, Boman A, Boman HG. Retro and retroenantio analogs of cecropin-melittin hybrids. Proc. Natl. Acad. Sci. USA. 1995;92:3449–3453.
65. Merrifield RB, Wade D, Boman HG. Antibiotic Peptides Containing D-Amino Acids. US5585353 A. 1996 Dec 17.
66. Anju G, Reetu G, Sudarshan K. Hanbook of Research on Diverse Applications of Nanotechnology in Biomedicine, Chemistry, and Engineering. Soni, Shivani; Hershey, PA, USA: 2015..
67. Stockwell VO, Duffy B. Use of antibiotics in plant agriculture. Rev. Sci. Tech. 2012;31:199–21079.
68. Badosa E, Ferre R, Planas M, Feliu L, Besalu E, Cabrefiga J, et al. A library of linear undecapeptides with bactericidal activity against phytopathogenic bacteria. Peptides. 2007;28:2276–2285.
69. Rubner MF, Yang SY, Qiu Y, Lynn C, Lally JM. Method for making medical devices having antimicrobial coatings thereon. US20140112994. 2014.Toxins 2015; 7:1126-1150.
70. Baghian A, Jaynes J, Enright F, Kousoulas KG. An amphipathic alpha-helical synthetic peptide analogue of melittin inhibits herpes simplex virus-1 (HSV-1)-induced cell fusion and virus spread. Peptides. 1997;18:177–183.
71. Wachinger M, Saermark T, Erfle V. Influence of amphipathic peptides on the HIV-1 production in persistently infected T lymphoma cells. FEBS Lett. 1992;309:235–241.
72. Hagenbucher S, Eisenring M, Meissle M, Romeis J. Interaction of transgenic and natural insect resistance mechanisms against Spodopteralittoralis in cotton. Pest Manag Sci. 2017;73:1670-1678.
73. Hagenbucher S, Eisenring M, Meissle M, Romeis J. Interaction of transgenic and natural insect resistance mechanisms against Spodopteralittoralis in cotton. PestManag Sci. 2017;73:1670-1678.
74. Ariane F Lacerda, Patrícia B. Pelegrini, Daiane M. de Oliveira, Érico A. R. Vasconcelos, and Maria F. Grossi-de-Sá.Anti-parasitic Peptides from Arthropods and their Application in Drug Therapy, Front Microbiol. 2016; 7: 91.
75. Elias Ferreira SabiáJúnior, Luis Felipe Santos Menezes, Israel Flor Silva de Araújo, and Elisabeth Ferroni Schwartz* Natural Occurrence in Venomous Arthropods of Antimicrobial Peptides Active against Protozoan Parasites, Toxins (Basel). 2019; 11: 563
76. Victoria Carter, Ann Underhill, Ibrahima Baber, LakamySylla, Mounirou Baby, Isabelle Larget-Thiery, AgnèsZettor, Catherine Bourgouin, ÜloLangel, et al, Killer Bee Molecules: Antimicrobial Peptides as Effector Molecules to Target Sporogonic Stages of Plasmodium PLoSPathog. 2013; 9: e1003790.
77. Nuno Vale, LuísaAguiar, Paula GomesAnti-microbial peptides: a new class of antimalarial drugs? Front Pharmacol. 2014; 5: 275.
78. Moreau SJ, Asgari S. Venom Proteins from Parasitoid Wasps and Their Biological Functions. Toxins (Basel). 2015;7:2385-2412.
79. Dotimas EM, Hamid KR, Hider RC, Ragnarsson U. Isolation and structure analysis of bee venom mast cell degranulating peptide. Biochim.Biophys.Acta. 1987;911:285–293.
80. Ziai MR, Russek S, Wang HC, Beer B, Blume AJ. Mast cell degranulating peptide: A multi-functional neurotoxin. J. Pharm. Pharmacol. 1990;42:457–461.
81. Sharma JN. Basic and clinical aspects of bradykinin receptor antagonists. Prog. Drug Res. 2014;69:1–14.
82. Shkenderov S, Koburova KAdolapin—A newly isolated analgetic and anti-inflammatory polypeptide from bee venom. Toxicon. 1982;20:317–321.
83. Kitamura H, Yokoyama M, Akita H, Matsushita K, Kurachi Y, Yamada M. Tertiapin potently and selectively blocks muscarinic K+ channels in rabbit cardiac myocytes. J. Pharmacol. Exp. Ther. 2000;293:196–205.
84. Vlasak R, Kreil G. Nucleotide sequence of cloned cDNAs coding for preprosecapin, a major product of queen-bee venom glands. Eur. J. Biochem. 1984;145:279–282.

85. Meng Y, Yang XX, Zhang JL, Yu DQ. A novel peptide from Apismelliferaand solid-phase synthesis of its analogue. Chin. Chem. Lett. 2012;23:1161–1164.


86. Mourelle D, Brigatte P, Bringanti LD, de Souza BM, Arcuri HA, Gomes PC, Baptista-Saidemberg NB, Ruggiero Neto J., Palma MS. Hyperalgesic and edematogenic effects of Secapin-2, a peptide isolated from Africanized honeybee (Apismellifera) venom. Peptides. 2014;59:4252.

87. Gauldie J, Hanson JM, Shipolini RA, Vernon CA. The structures of some peptides from bee venom. Eur. J. Biochem. 1978;83:405–410
88. Vick JA, Shipman WH, Brooks R., Jr. Beta adrenergic and anti-arrhythmic effects of cardiopep, a newly isolated substance from whole bee venom. Toxicon. 1974;12:139–144.
89. Monsalve RI, Lu G, King TP. Expressions of recombinant venom allergen, antigen 5 of yellowjacket (Vespula vulgaris) and paper wasp (V.annularis), in bacteria or yeast. Protein Expr.Purif. 1999;16:410–416.
90. Konno K, Hisada M, Fontana R, Lorenzi CC, Naoki H, Itagaki Y, Miwa A, Kawai N, Nakata Y, Yasuhara T, et al. Anoplin, a novel antimicrobial peptide from the venom of the solitary wasp Anopliussamariensis. Biochim.Biophys.Acta. 2001;1550:70–80.
91. Krishnakumari V, Nagaraj R. Antimicrobial and hemolytic activities of crabrolin, a 13-residue peptide from the venom of the European hornet, Vespa crabro, and its analogs. J. Pept. Res. 1997;50:8893.
92. Konno K, Rangel M, Oliveira JS, Dos Santos Cabrera MP, Fontana R, Hirata IY, Hide I, Nakata Y, Mori K, Kawano M, et al. Decoralin, a novel linear cationic alpha-helical peptide from the venom of the solitary eumenine wasp Oreumenesdecoratus. Peptides. 2007;28:2320–2327.
93. Konno K, Hisada M, Naoki H, Itagaki Y, Fontana R, Rangel M, Oliveira JS, Cabrera MP, Neto JR, Hide I, et al. Eumenitin, a novel antimicrobial peptide from the venom of the solitary eumenine wasp Eumenesrubronotatus. Peptides. 2006;27:2624–2631.
94. Cerovsky V, Hovorka O, Cvacka J, Voburka Z, Bednarova L, Borovickova L, Slaninova J, Fucik V. Melectin: A novel antimicrobial peptide from the venom of the cleptoparasitic bee Melecta albifrons. Chembiochem. 2008;9:2815–2821.
95. Chionis K, Kostas Chionis , DimitriosKrikorian, Anna-IriniKoukkoun, Maria Sakarellos-Daitsiotis , Eugenia Panou-Pomonis Synthesis and Biological Activity of Lipophilic Analogs of the Cationic Antimicrobial Active Peptide Anoplin.J PeptSci. 2016;22:731-736
96. Primon-Barros M, Animal Venom Peptides: Potential for New Antimicrobial Agents.JoséMacedoA.Curr Top Med Chem. 2017;17:1119-1156
97. Kim Y, Yangseon Kim, Minky Son , Eun-Young Noh , Soonok Kim, Changmu Kim et al MP-V1 From the Venom of Social Wasp Vespula Vulgaris Is a De Novo Type of Mastoparan That Displays Superior Antimicrobial Activities 2016;21:5
98. Xinwang Yang 1, Ying Wang, Wen-Hui Lee, Yun Zhang Antimicrobial Peptides From the Venom Gland of the Social Wasp Vespa Tropica. Toxicon 2013;74:151-7.
99. Jia F, Wang J, Peng J, Zhao P, Kong Z, Wang K, Yan W, Wang R. D-amino acid substitution enhances the stability of antimicrobial peptide polybia-CP. ActaBiochimBiophys Sin (Shanghai). 2017;49:916-925.
100. Pak SC. An Introduction to the Toxins Special Issue on Bee and Wasp Venoms: Biological Characteristics and Therapeutic Application. Toxins (Basel). 2016;8:315.

101. Moreno M, Giralt E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan. Toxins (Basel). 2015;7:1126-1150.

102. Sample CJ, Hudak KE, Barefoot BE, et al. A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses. Peptides. 2013;48:96-105.

103. 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;24:2997.
104. Memariani H, Memariani M, Moravvej H, Shahidi-Dadras M. Melittin: a venom-derived peptide with promising anti-viral properties. Eur J ClinMicrobiol Infect Dis. 2020;39:5-17.
105. Agarwal G, Gabrani R. Antiviral Peptides: Identification and Validation. Int J Pept Res Ther. 2020;1-20.
106. Roskens VA, Carpenter JM, Pickett KM, Ballif BA. Preservation of field samples for enzymatic and proteomic characterization: analysis of proteins from the trophallactic fluid of hornets and yellowjackets. J Proteome Res. 2010;9:5484-91.
107. Gonçalves J, Rangel M, Biolchi A, Alves E, Moreira K, Silva L, Mortari M. Antinociceptive properties of the mastoparan peptide Agelaia-MPI isolated from social wasps. Toxicon. 2016;120:15-21.
108.
109. Pucci L, Lucchesi D, Fotino C, Grupillo M, Miccoli R, Penno G, Del Prato S. Il polimorfismo PlA1/PlA2 dell'integrina Beta 3 non contribuisce al rischio di complicanze micro- e macrovascolarineldiabetetipo 1 e tipo 2 [Integrin Beta 3 PlA1/PlA2 polimorphism does not contribute to complications in both type 1 and type 2 diabetes]. G ItalNefrol. 2003;20:461-9.

110. Del Prato S, Tiengo A. The importance of first-phase insulin secretion: implications for the therapy of type 2 diabetes mellitus. Diabetes Metab Res Rev. 2001;17:164-74.

111. Sarmiento BE, Santos Menezes LF, Schwartz EF. Insulin Release Mechanism Modulated by Toxins Isolated from Animal Venoms: From Basic Research to Drug Development Prospects. Molecules. 2019;24:1846.

112. Hou, June Chunqiu et al. Insulin granule biogenesis, trafficking and exocytosis. Vitamins and hormones, 2009; 80: 473-506.
113. Melo da Cunha JDS, Alfredo TM, Dos Santos JM, Alves Junior VV, Rabelo LA, Lima ES, Boleti APA, Carollo CA, Dos Santos EL, de Picoli Souza K. Antioxidant, anti-hyperglycemic, and anti-diabetic activity of Apismellifera bee tea. PLoS One. 2018;13:e0197071.
114. Mousavi SM, Imani S, Haghighi S, Mousavi SE, Karimi A. Effect of Iranian Honey bee (Apismellifera) Venom on Blood Glucose and Insulin in Diabetic Rats. J Arthropod Borne Dis. 2012;6:136-43.
115. Saba E, Shafeeq T, Irfan M,. Anti-Inflammatory Activity of Crude Venom Isolated from Parasitoid Wasp, Braconhebetor Say. Mediators Inflamm. 2017;697:81-94.

116. Seabrooks L, Hu L. Insects: an underrepresented resource for the discovery of biologically active natural products. Acta Pharm Sin B. 2017;7:409-426.

117. Bordon KCF, Cologna CT, Fornari-Baldo EC, et al. From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery. Front Pharmacol. 2020;11:1132.

118. Cheon SY, Chung KS, Roh SS, Cha YY, An HJ. Bee Venom Suppresses the Differentiation of Preadipocytes and High Fat Diet-Induced Obesity by Inhibiting Adipogenesis. Toxins (Basel). 2017;10:9.

119. Mars J Yang 1, Wen-Yuh Lin, Kuang-Hui Lu, Wu-Chun Tu Evaluating Anti-oxidative Activities of Amino Acid Substitutions on mastoparan-BPeptides 2011;32:2037-43.
120. José Palmieri M, RibeiroBarroso A, Fonseca Andrade-Vieira L, Monteiro MC, Martins Soares A, Souza Cesar PH, Aparecida Braga M, Cardoso Trento MV, Marcussi S, ChammaDavideL.occidentalis and Polybiafastidiosa venom: a cytogenotoxic approach of effects on human and vegetal cells. Drug ChemToxicol. 2019:1-9.
121. Schwartz EF, Elisabeth F Schwartz 1, Caroline B F Mourão, Karla G Moreira, Thalita S Camargos, Márcia R MortariArthropod Venoms: A Vast Arsenal of Insecticidal Neuropeptide Biopolymers 2012;98:385-405.
122. Henry TJ. Revision of the plant bug genus tytthus (hemiptera, heteroptera, miridae, phylinae). Zookeys. 2012;220:1-114.
123. Kazuma K, KoheiKazuma , Kenji Ando , Ken-Ichi Nihei , Xiaoyu Wang , Marisa Rangel , Marcia Regina Franzolin , Kanami Mori-Yasumoto , Setsuko Sekita , Makoto Kadowaki , MotoyoshiSatake , Katsuhiro Konno Peptidomic Analysis of the Venom of the Solitary Bee XylocopaAppendiculatacircumvolans. J Venom Animal ToxinsIncl Trop Dis 2017;23:40.
124. Lopes KS,KamilaSoares Lopes , Gabriel AvohayAlves Campos , Luana Cristina Camargo , Adolfo Carlos Barros de Souza ,et al, Characterization of Two Peptides Isolated From the Venom of Social WaspChartergelluscommunis (Hymenoptera: Vespidae): Influence of Multiple Alanine Residues and C-terminal Amidation on Biological Effects Peptides2017;95:84-93.
125. Deuis JR, Jennifer R Deuis , Alexander Mueller , Mathilde R Israel , Irina Vetter The Pharmacology of Voltage-Gated Sodium Channel Activator Neuropharmacology 2017;127:87-108.
126. Welton RE, Williams DJ, Liew D. Injury trends from envenoming in Australia, 2000-2013.Intern Med J. 2017;47:170-176
127. Graler MH, Goetzl EJ. Lysophospholipids and their G protein-coupled receptors in inflammation and immunity. Biochim.Biophys.Acta. 2002;1582:168–174.
128. Doery HM, Pearson JE. Phospholipase B in snake venoms and bee venom. Biochem. J. 1964;92:599–602.
129. Girish KS, Kemparaju K. The magic glue hyaluronan and its eraser hyaluronidase: A biological overview. Life Sci. 2007;80:1921–1943.
130. Uzair, B ,BushraUzair , RabiaBushra , Barkat Ali Khan , SarwatZareen , FehmidaFasim Potential Uses of Venom Proteins in Treatment of HIVProtein PeptLett 2018;25:619-625.
131. Mendes MA, De Souza BM, Marques MR, Palma MS. Structural and biological characterization of two novel peptides from the venom of the neotropical social wasp Agelaiapallipespallipes. Toxicon. 2004;44:67–74.
132. Han SM, Lee KG, Pak SC. Effects of cosmetics containing purified honeybee (Apismellifera L.) venom on acne vulgaris. J. Integr. Med. 2013;11:320–326.
133. Cho SY, Shim SR, Rhee HY, Park HJ, Jung WS, Moon SK, Park JM, Ko CN, Cho KH, Park SU. Effectiveness of acupuncture and bee venom acupuncture in idiopathic Parkinson’s disease. Parkinsonism Relat.Disord. 2012;18:948–952.
134. AlvesEM, Heneine LGD, Pesquero JL, Albuquerque MLD. Pharmaceutical Composition Containin an Apitoxin Fraction and Use Thereof. WO2011041865. 2011;7:1126-115
135. Lee MS, Pittler MH, Shin BC, Kong JC, Ernst E. Bee venom acupuncture for musculoskeletal pain: A review. J. Pain. 2008;9:289–297.
136. Huh J, Kang JW, Nam D, Baek YH, Choi DY, Park DS, Lee JD. Melittin suppresses VEGF-A-induced tumor growth by blocking VEGFR-2 and the COX-2-mediated MAPK signaling pathway. J. Nat. Prod. 2012;75:1922–1929.
137. Yang X, Zhu H,Ge Y, Liu J, Cai J, Qin Q, et al. Melittin enhances radiosensitivity of hypoxic head and neck squamous cell carcinoma by suppressing HIF-1alpha. Tumour Biol. 2014;35:10443–10448.
138. Dunn RD, Weston KM, Longhurst TJ, Lilley GG, Rivett DE., Hudson PJ, et al . Antigen binding and cytotoxic properties of a recombinant immunotoxin incorporating the lytic peptide, melittin. Immunotechnology. 1996;2:229–240.
139. Zhao X, Yu Z, Dai W, Yao Z, Zhou W, Zhou W, Zhou J, Yang Y, Zhu Y, Chen S, et al. Construction and characterization of an anti-asialoglycoprotein receptor single-chain variable-fragment-targeted melittin. Biotechnol. Appl. Biochem. 2011;58:405–411
140. Jin H, Li C, Li D, Cai M, Li Z, Wang S, et al . Construction and characterization of a CTLA-4-targeted scFv-melittin fusion protein as a potential immune suppressive agent for organ transplant. Cell Biochem.Biophys. 2013;67:1067–1074.
141. HolleL,Song W, Holle E, Wei Y, Wagner T, Yu X. A matrix metalloproteinase 2 cleavable melittin/avidin conjugate specifically targets tumor cells in vitro and in vivo. Int. J. Oncol. 2003;22:93–98
142. Holle L, Song W, Holle E, Wei Y, Li J, Wagner TE, et al. In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein. Int. J. Oncol. 2009;35:829–835.
143. Yang L, Cui F, Shi K, Cun, Wang R. Design of high payload PLGA nanoparticles containing melittin/sodium dodecyl sulfate complex by the hydrophobic ion-pairing technique. Drug Dev. Ind. Pharm. 2009;35:959–968.
144. Hu H., Chen D, Liu Y, Deng Y, Yang S, Qiao M, Zhao J, Zhao X. Target ability and therapy efficacy of immune liposomes using a humanized anti-hepatoma disulfide-stabilized Fv fragment on tumor cells. J. Pharm. Sci. 2006;95:192–199.
145. Barrajon-Catalan Menendez-Gutierrez MP, Falco A, Carrato A, Saceda M. Micol V. Selective death of human breast cancer cells by lytic immune liposomes: Correlation with their HER2 expression level. Cancer Lett. 2010;290:192–203.
146. Popplewell JF, Swann MJ, Freeman NJ, McDonnell C, Ford RC. Quantifying the effects of melittin on liposomes. Biochim.Biophys.Acta. 2007;1768:13–20.
147. Soman NR, Lanza GM, Heuser JM, Schlesinger PH, Wickline SA. Synthesis and characterization of stable fluorocarbon nanostructures as drug delivery vehicles for cytolytic peptides. Nano Lett. 2008;8:1131–1136.
148. Soman NR, Baldwin SL, Hu G, Marsh JN, Lanza GM, Heuser JE, Arbeit JM, Wickline SA, Schlesinger PH. Molecularly targeted nanocarriers deliver the cytolytic peptide melittinspecifically to tumor cells in mice, reducing tumor growth. J. Clin. Investig. 2009;119:2830–2842.
149. Schäper S, Wendt H, Bamberger J, Sieber V, Schmid J, Becker A. A Bi-functional UDP-Sugar 4-Epimerase Supports Biosynthesis of Multiple Cell Surface Polysaccharides in Sinorhizobiummeliloti. J Bacteriol. 2019;201:00801-18.
150. Müller UR. Bee venom allergy in beekeepers and their family members. CurrOpin Allergy ClinImmunol. 2005;5:343-7.
151. Müller UR,2011Hymenoptera Venom Proteins and Peptides for Diagnosis and Treatment of Venom Allergic Patients Inflamm Allergy Drug Targets 2011;10:420-8.
152. Heppt MV, Clanner-Engelshofen BM, Marsela E, Wessely A, Kammerbauer C, Przybilla B, French LE, Berking C, Reinholz M. Comparative analysis of the phototoxicity induced by BRAF inhibitors and alleviation through antioxidants. PhotodermatolPhotoimmunolPhotomed. 2020;36:126-134.
153. Becerril-Angeles M, Nunez-Velazquez M, Marin-Martinez J; Grupo del ProgramaNacional de Control de la AbejaAfricanizada SAGARPA. Valoracion median epruebascutaneas de la hipersensibilidad al veneno de abeja en apicultores [Assessment of hypersensitivity to honey-bee venom in beekeepers by skin tests]. Rev Alerg Mex. 2013;60:164-7.
154. MunstedtK, Using Bee Products for the Prevention and Treatment of Oral Mucositis Induced by Cancer Treatment 2019;24:3023.
155. Wu TM, Li ML. The cytolytic action of all-D mastoparan M on tumor cell lines. Int. J. Tissue React. 1999;21:35–42.
156. Wu CW, Kirshenbaum K, Sanborn TJ, Patch JA, Huang K, Dill KA, Zuckermann RN, Barron AE. Structural and spectroscopic studies of peptoid oligomers with alpha-chiral aliphatic side chains. J Am Chem Soc. 2003;125:13525-30.
157. Hussein AA, Nabil ZI, Zalat SM, Rakha MK. Comparative study of the venoms from three species of bees: effects on heart activity and blood. J Nat Toxins. 2001;10:343-57.
158. Lambeau G, Ancian P, Nicolas JP, Beiboer SH, Moinier D, Verheij H, Lazdunski M. Structural elements of secretory phospholipases A2 involved in the binding to M-type receptors. J Biol Chem. 1995;270:5534-40.
159. Christen V, Mittner F, Fent K. Molecular Effects of Neonicotinoids in Honey Bees (Apismellifera). Environ Sci Technol. 2016 ;50:4071-81.
160. Mohammed SEA, Kabbashi AS, Koko WS, Ansari MJ, Adgaba N, Al-Ghamdi A. In vitro activity of some natural honeys against Entamoebahistolytica and Giardia lamblia trophozoites. Saudi J Biol Sci. 2019;26:238-243.
161. Ahmad F, Seerangan P, Mustafa MZ, Osman ZF, Abdullah JM, Idris Z. Anti-Cancer Properties of Heterotrigonaitama sp. Honey Via Induction of Apoptosis in Malignant Glioma Cells. Malays J Med Sci. 2019;26:30-39.
162. ShiassiArani F, Karimzadeh L, Ghafoori SM, Nabiuni M. Anti-mutagenic and Synergistic Cytotoxic Effect of Cisplatin and Honey Bee Venom on 4T1 Invasive Mammary Carcinoma Cell Line. AdvPharmacol Sci. 2019;:758:13-18.
163. SeyhanMF, Y?lmaz E, Timirci-Kahraman O, Sayg?l? N, K?sakesen H?, Eronat AP, Ceviz AB, BilgiçGazioglu S, Y?lmaz-Aydogan H, Öztürk O. Anatolian honey is not only sweet but can also protect from breast cancer: Elixir for women from artemis to present. IUBMB Life. 2017;69:677-688.
164. Uddin MB, Inhibitory Effects of Bee Venom and Its Components Against Viruses in vitro in vivo 2016;54:853-866.
165. Brudzynski K, Antibacterial Compounds of Canadian Honeys Target Bacterial Cell Wall Inducing Phenotype Changes, Growth Inhibition and Cell Lysis That Resemble Action of ?-Lactam Antibiotics2014;9:e106967.
166. Kustiawan PM, In Vitro Cytotoxicity of Indonesian Stingless Bee Products Against Human Cancer Cell Lines J Trop Biomed 2014;4:549-56.
167. Moskwa J, Polish Natural Bee Honeys Are Anti-Proliferative and Anti-Metastatic Agents in Human Glioblastoma Multiforme U87MG Cell Line2014;9:e90533
168. Park D .Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells 2016;22:971-83.

169. Panda, S, and IEhsan. Molecular docking studies of snake venom serine protease of sharp –nosed pit viper with hesperetin. Asian Journal of Pharmaceutical and Clinical Research, 2018; 11: 457-61.

170. Hymenoptera – Wikipedia https://en.wikipedia.org/wiki/Hymenoptera
171. Hymenopteran | insect | Britannica, www.britannica.com
172. Donald R. Hoffman, in Encyclopedia of Immunology (Second Edition), 1998.

173. Baek, JH, Lee, SH. Identification and characterization of venom proteins of two solitary wasps. Toxicon 2010;56, 554–562.

174. Kumar, RB, and MX. Suresh. Neurotox: A unique database for animal neurotoxins. International Journal of Pharmacy and Pharmaceutical Sciences2015;7: 351-4.
175. Preet, P Peptides: A new therapeutic approach. International Journal of Current Pharmaceutical Research2018; 10: 29-34.
176. Baek, JH,Woo, TH, Kim, CB,et al . Differential gene expression profiles in the venom
gland/sac of Orancistro cerus drewseni (Hymenoptera: Eumenidae). Arch. Insect Biochem. Physiol. 2009;71, 205–222.

177. Baek, JH, Lee, SH. Differential gene expression profiles in the venom gland/sac of Eumenespomiformis (Hymenoptera: Eumenidae). Toxicon 2010;55,1147–1156.
178. Dos Santos, LD, Santos, KS, Pinto, J.R.A, et al. Profiling the proteome of the venom from the social wasp Polybiapaulista: A clue to understand the envenoming mechanism. J. Proteome Res. 2010, 9, 3867–3877.
179. Liu, ZR, Chen, SG, Zhou, Y,et al. Deciphering the venomictranscriptome of killer-wasp Vespa velutina. Sci Rep. 2015, 5.
180. Yoon, KA,Kim, K, Nguyen, P, et al Comparative bioactivities of mastoparans from social hornets Vespa crabro and Vespa analis. J. Asia Pac. Entomol. 2015;18:825–829.
181. Liu, ZR, Chen, SG, Zhou, Y,et al. Deciphering the venomictranscriptome of killer-wasp Vespa velutina. Sci Rep. 2015, 5.

182. Konno, K, Hisada, M, Itagaki, Y. Isolation and structure of pompilidotoxins, novel peptide neurotoxins in solitary wasp venoms. Biochem. Biophys. Res. Commun. 1998; 250:612–616.
183.Asawale, KY, MC Mehta, and PSUike. Drug utilization analysis of anti-snake venom at a tertiary care centre in central Maharasthtra: A 3-year retrospective study. Asian Journal of Pharmaceutical and Clinical Research,2018; 11:134-7.
184. Moreno M, Giralt E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan. Toxins (Basel). 2015;7:1126-50.
Statistics
6 Views | Downloads
Citations
How to Cite
Upadhyay, R. K., and S. SHARMA. “Hornet, Wasp and Bee Toxin Peptides: Biological Activity, Pharmaceutical and Therapeutic Uses: Hornet, Wasp and Bee Toxin Peptides”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 13, no. 4, Feb. 2021, doi:10.22159/ijpps.2021v13i4.40473.
Section
Review Article(s)