BEE VENOM AND ITS BIOLOGICAL EFFECTS

Year 2022, , 86 - 105, 30.06.2022

Nurten Abacı , İlkay Erdoğan Orhan

https://doi.org/10.38093/cupmap.1127949

Cited By: 1

Abstract

Apitherapy is defined as “the use of Apis mellifera L. products such as royal jelly, pollen, honey, propolis, beeswax, and bee venom in the treatment of ailments”. Although honey is the primary product acquired, other bee products are also obtained in Turkey. These commodities, in addition to being utilized as nutrition, have been employed to promote human health since ancient times owing to the biologically active compounds they contain. Bee venom is increasingly commonly used in apitherapy and has a wide range of biological effects including antiviral, antidiabetic, anticancer, antirheumatic, anticoagulant, antibacterial, anti-cancer, anti-aging, neuroprotective, analgesic, antioxidant, hepatoprotective, and anti-asthmatic properties. According to the literature, bee venom has promising biological implications for human health, which constitutes the topic of this review.

Keywords

bee venom, apitoxin, apitherapy, bee venom acupuncture, melittin

References

• 1. An, H. J., Lee, W. R., Kim, K. H., Kim, J. Y., Lee, S. J., Han, S. M., Lee, K. G., Lee, C. K., & Park, K. K. (2014). Inhibitory effects of bee venom on Propionibacterium acnes-induced inflammatory skin disease in an animal model. International journal of molecular medicine, 34(5), 1341-1348. https://doi.org/10.3892/ijmm.2014.1933
• 2. Andersson, G. B. (1999). Epidemiological features of chronic low-back pain. The lancet, 354(9178), 581-585. https://doi.org/10.1016/S0140-6736(99)01312-4
• 3. Arteaga, V., Lamas, A., Regal, P., Vázquez, B., Miranda, J. M., Cepeda, A., & Franco, C. M. (2019). Antimicrobial activity of apitoxin from Apis mellifera in Salmonella enterica strains isolated from poultry and its effects on motility, biofilm formation and gene expression. Microbial Pathogenesis, 137, 103771. https://doi.org/10.1016/j.micpath.2019.103771
• 4. Azam, M. N. K., Ahmed, M. N., Biswas, S., Ara, N., Rahman, M. M., Hirashima, A., & Hasan, M. N. (2018). A review on bioactivities of honey bee venom. Annual Research & Review in Biology, 1-13. https://doi.org/10.9734/ARRB/2018/45028 5. Babaie, M., Mehrabi, Z., & Mollaei, A. (2020). Partial purification and characterization of antimicrobial effects from snake (Echis carinatus), scorpion (Mesosobuthus epues) and bee (Apis mellifera) venoms. Iranian Journal of Medical Microbiology, 14(5), 460-477. https://doi.org/10.30699/ijmm.14.5.460
• 6. Badr, G., Hozzein, W. N., Badr, B. M., Al Ghamdi, A., Saad Eldien, H. M., & Garraud, O. (2016). Bee venom accelerates wound healing in diabetic mice by suppressing activating transcription factor‐3 (ATF‐3) and inducible nitric oxide synthase (iNOS)‐mediated oxidative stress and recruiting bone marrow‐derived endothelial progenitor cells. Journal of Cellular Physiology, 231(10), 2159-2171. https://doi.org/10.1002/jcp.25328
• 7. Baek, Y. H., Huh, J. E., Lee, J. D., & Park, D. S. (2006). Antinociceptive effect and the mechanism of bee venom acupuncture (Apipuncture) on inflammatory pain in the rat model of collagen-induced arthritis: Mediation by α2-Adrenoceptors. Brain research, 1073, 305-310. https://doi.org/10.1016/j.brainres.2005.12.086
• 8. Behroozi, J., Divsalar, A., & Saboury, A. A. (2014). Honey bee venom decreases the complications of diabetes by preventing hemoglobin glycation. Journal of Molecular Liquids, 199, 371-375. https://doi.org/10.1016/j.molliq.2014.09.034
• 9. Bellik, Y. (2015). Bee venom: its potential use in alternative medicine. Anti-infective agents, 13(1), 3-16. https://doi.org/10.2174/2211352513666150318234624
• 10. Cai, M., Choi, S. M., & Yang, E. J. (2015). The effects of bee venom acupuncture on the central nervous system and muscle in an animal hSOD1G93A mutant. Toxins, 7(3), 846-858. https://doi.org/10.3390/toxins7030846
• 11. Chan, W., He, B., Wang, X., & He, M. L. (2020). Pandemic COVID-19: Current status and challenges of antiviral therapies. Genes & Diseases, 7(4), 502-519. https://doi.org/https://doi.org/10.1016/j.gendis.2020.07.001
• 12. Chen, M., Aoki Utsubo, C., Kameoka, M., Deng, L., Terada, Y., Kamitani, W., Sato, K., Koyanagi, Y., Hijikata, M., & Shindo, K. (2017). Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane. Scientific reports, 7(1), 1-8. https://doi.org/10.1038/s41598-017-16130-w
• 13. Cheng, Y., & Ren, X. (2004). Arrhythmia by bee sting acupuncture. Journal of Clinical Acupuncture and Moxibustion, 20, 54.
• 14. Cherbuliez, T. (2013). Apitherapy–the use of honeybee products. In Biotherapy-History, Principles and Practice (pp. 113-146). Springer.
• 15. Cherniack, E. P., & Govorushko, S. (2018). To bee or not to bee: The potential efficacy and safety of bee venom acupuncture in humans. Toxicon, 154, 74-78. https://doi.org/10.1016/j.toxicon.2018.09.013
• 16. Choi, M. S., Park, S., Choi, T., Lee, G., Haam, K. K., Hong, M. C., Min, B. I., & Bae, H. (2013). Bee venom ameliorates ovalbumin induced allergic asthma via modulating CD4+ CD25+ regulatory T cells in mice. Cytokine, 61(1), 256-265. https://doi.org/10.1016/j.cyto.2012.10.005
• 17. Chu, S.-T., Cheng, H.-H., Huang, C.-J., Chang, H.-C., Chi, C.-C., Su, H.-H., Hsu, S.-S., Wang, J.-L., Chen, I.-S., & Liu, S.-I. (2007). Phospholipase A2-independent Ca2+ entry and subsequent apoptosis induced by melittin in human MG63 osteosarcoma cells. Life sciences, 80(4), 364-369. https://doi.org/10.1016/j.lfs.2006.09.024
• 18. De Graaf, D. C., Brochetto Braga, M. R., de Abreu, R. M. M., Blank, S., Bridts, C. H., De Clerck, L. S., Devreese, B., Ebo, D. G., Ferris, T. J., & Hagendorens, M. M. (2021). Standard methods for Apis mellifera venom research. Journal of Apicultural Research, 1-31. https://doi.org/10.1080/00218839.2020.1801073
• 19. Dudler, T., Chen, W. Q., Wang, S., Schneider, T., Annand, R. R., Dempcy, R. O., Crameri, R., Gmachl, M., Suter, M., & Gelb, M. H. (1992). High-level expression in Escherichia coli and rapid purification of enzymatically active honey bee venom phospholipase A2. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism, 1165(2), 201-210. https://doi.org/10.1016/0005-2760(92)90188-2
• 20. Fenard, D., Lambeau, G., Valentin, E., Lefebvre, J. C., Lazdunski, M., & Doglio, A. (1999). Secreted phospholipases A 2, a new class of HIV inhibitors that block virus entry into host cells. The Journal of clinical investigation, 104(5), 611-618. https://doi.org/10.1172/JCI6915
• 21. Guo, S. a., & DiPietro, L. A. (2010). Factors affecting wound healing. Journal of dental research, 89(3), 219-229. https://doi.org/10.1177/0022034509359125
• 22. Han, S. M., Hong, I. P., Woo, S. O., Chun, S. N., Park, K. K., Nicholls, Y. M., & Pak, S. C. (2015). The beneficial effects of honeybee-venom serum on facial wrinkles in humans. Clinical interventions in aging, 10, 1587. https://doi.org/10.2147/CIA.S84940
• 23. Han, S. M., Pak, S. C., Nicholls, Y. M., & Macfarlane, N. (2016). Evaluation of anti‐acne property of purified bee venom serum in humans. Journal of cosmetic dermatology, 15(4), 324-329. https://doi.org/10.1111/jocd.12227
• 24. Han, S. M., Park, K. K., Nicholls, Y. M., Macfarlane, N., & Duncan, G. (2013). Effects of honeybee (Apis mellifera) venom on keratinocyte migration in vitro. Pharmacognosy Magazine, 9(35), 220. https://doi.org/10.4103/0973-1296.113271
• 25. Hong, S. J., Rim, G. S., Yang, H. I., Yin, C. S., Koh, H. G., Jang, M. H., Kim, C. J., Choe, B. K., & Chung, J. H. (2005). Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis. Toxicon, 46(1), 39-45. https://doi.org/10.1016/j.toxicon.2005.03.015
• 26. Hossen, M., Shapla, U. M., Gan, S. H., & Khalil, M. (2017). Impact of bee venom enzymes on diseases and immune responses. Molecules, 22(1), 25. https://doi.org/10.3390/molecules22010025
• 27. Hozzein, W. N., Badr, G., Badr, B. M., Allam, A., Al Ghamdi, A., Al-Wadaan, M. A., & Al-Waili, N. S. (2018). Bee venom improves diabetic wound healing by protecting functional macrophages from apoptosis and enhancing Nrf2, Ang-1 and Tie-2 signaling. Molecular immunology, 103, 322-335. https://doi.org/10.1016/j.molimm.2018.10.016
• 28. Jo, M., Park, M. H., Kollipara, P. S., An, B. J., Song, H. S., Han, S. B., Kim, J. H., Song, M. J., & Hong, J. T. (2012). Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicology and applied pharmacology, 258(1), 72-81. https://doi.org/10.1016/j.taap.2011.10.009
• 29. Kang, S.-Y., Kim, C.-Y., Roh, D.-H., Yoon, S.-Y., Park, J.-H., Lee, H.-J., Beitz, A. J., & Lee, J.-H. (2011). Chemical stimulation of the ST36 acupoint reduces both formalin-induced nociceptive behaviors and spinal astrocyte activation via spinal alpha-2 adrenoceptors. Brain Research Bulletin, 86(5-6), 412-421. https://doi.org/10.1016/j.brainresbull.2011.08.012
• 30. Kasozi, K. I., Niedbała, G., Alqarni, M., Zirintunda, G., Ssempijja, F., Musinguzi, S. P., Usman, I. M., Matama, K., Hetta, H. F., Mbiydzenyuy, N. E., Batiha, G. E. S., Beshbishy, A. M., & Welburn, S. C. (2020). Bee Venom—A Potential Complementary Medicine Candidate for SARS-CoV-2 Infections [Review]. Frontiers in public health, 8. https://doi.org/10.3389/fpubh.2020.594458
• 31. Kharroubi, A. T., & Darwish, H. M. (2015). Diabetes mellitus: The epidemic of the century. World journal of diabetes, 6(6), 850. https://doi.org/10.4239/wjd.v6.i6.850
• 32. Kim, H.-W., Kwon, Y.-B., Ham, T.-W., Roh, D.-H., Yoon, S.-Y., Lee, H.-J., Han, H.-J., Yang, I.-S., Beitz, A. J., & Lee, J.-H. (2003). Acupoint stimulation using bee venom attenuates formalin-induced pain behavior and spinal cord fos expression in rats. Journal of veterinary medical science, 65(3), 349-355. https://doi.org/10.1292/jvms.65.349
• 33. Kim, H. W., Kwon, Y. B., Han, H. J., Yang, I. S., Beitz, A. J., & Lee, J. H. (2005). Antinociceptive mechanisms associated with diluted bee venom acupuncture (apipuncture) in the rat formalin test: involvement of descending adrenergic and serotonergic pathways. Pharmacological research, 51(2), 183-188. https://doi.org/10.1016/j.phrs.2004.07.011
• 34. Kim, H. Y., Jo, M. J., Nam, S. Y., Kim, K. M., Choi, M. B., & Lee, Y. H. (2020). Evaluating the effects of honey bee (Apis mellifera L.) venom on the expression of insulin sensitivity and inflammation‐related genes in co‐culture of adipocytes and macrophages. Entomological Research, 50(5), 236-244. https://doi.org/10.1111/1748-5967.12431
• 35. Kim, J., Ochoa, M. T., Krutzik, S. R., Takeuchi, O., Uematsu, S., Legaspi, A. J., Brightbill, H. D., Holland, D., Cunliffe, W. J., & Akira, S. (2002). Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. The Journal of Immunology, 169(3), 1535-1541. https://doi.org/10.4049/jimmunol.169.3.1535
• 36. Kim, J. Y., Leem, J., & Park, K. K. (2020). Antioxidative, antiapoptotic, and anti-inflammatory effects of apamin in a murine model of lipopolysaccharide-induced acute kidney injury. Molecules, 25(23), 5717. https://doi.org/10.3390/molecules25235717
• 37. Ko, S. H., Oh, H. M., Kwon, D. Y., Yang, J. E., Kim, B. J., Ha, H. J., Lim, E. J., Oh, M. S., Son, C. G., & Lee, E. J. (2022). Incidence Rate of Bee Venom Acupuncture Related Anaphylaxis: A Systematic Review. Toxins, 14(4), 238. https://doi.org/10.3390/toxins14040238
• 38. Kurek Górecka, A., Komosinska Vassev, K., Rzepecka Stojko, A., & Olczyk, P. (2020). Bee venom in wound healing. Molecules, 26(1), 148. https://doi.org/10.3390/molecules26010148
• 39. Kwon, Y.-B., Kang, M.-S., Han, H.-J., Beitz, A. J., & Lee, J.-H. (2001). Visceral antinociception produced by bee venom stimulation of the Zhongwan acupuncture point in mice: role of α2 adrenoceptors. Neuroscience letters, 308(2), 133-137. https://doi.org/10.1016/s0304-3940(01)01989-9
• 40. Lee, E. J., Ahn, Y. C., Kim, Y. I., Oh, M. S., Park, Y. C., & Son, C. G. (2020). Incidence Rate of Hypersensitivity Reactions to Bee-Venom Acupuncture. Frontiers in pharmacology, 1575. https://doi.org/10.3389/fphar.2020.545555
• 41. Lee, G., & Bae, H. (2016). Anti-inflammatory applications of melittin, a major component of bee venom: Detailed mechanism of action and adverse effects. Molecules, 21(5), 616. https://doi.org/10.3390/molecules21050616
• 42. Lee, H., Lee, E. j., Kim, H., Lee, G., Um, E. J., Kim, Y., Lee, B. Y., & Bae, H. (2011). Bee venom-associated Th1/Th2 immunoglobulin class switching results in immune tolerance of NZB/W F1 murine lupus nephritis. American journal of nephrology, 34(2), 163-172. https://doi.org/10.1159/000329731
• 43. Lee, W. R., Kim, K. H., An, H. J., Kim, J. y., Chang, Y. C., Chung, H., Park, Y. Y., Lee, M. L., & Park, K. k. (2014). The protective effects of Melittin on Propionibacterium acnes–induced inflammatory responses in vitro and in vivo. Journal of Investigative Dermatology, 134(7), 1922-1930. https://doi.org/10.1038/jid.2014.75
• 44. Lee, W. R., Park, J. H., Kim, K. H., Park, Y. Y., Han, S. M., & Park, K. k. (2011). Protective effects of melittin on transforming growth factor-β1 injury to hepatocytes via anti-apoptotic mechanism. Toxicology and applied pharmacology, 256(2), 209-215. https://doi.org/10.1016/j.taap.2011.08.012
• 45. Li, B., Gu, W., Zhang, C., Huang, X. Q., Han, K. Q., & Ling, C. Q. (2006). Growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL-7402 induced by melittin. Oncology Research and Treatment, 29(8-9), 367-371. https://doi.org/10.1159/000094711
• 46. Lyu, C., Fang, F., & Li, B. (2019). Anti-tumor effects of melittin and its potential applications in clinic. Current Protein and Peptide Science, 20(3), 240-250. https://doi.org/10.2174/1389203719666180612084615
• 47. Männle, H., Hübner, J., & Münstedt, K. (2020). Beekeepers who tolerate bee stings are not protected against SARS-CoV-2 infections. Toxicon, 187, 279-284. https://doi.org/10.1016/j.toxicon.2020.10.004
• 48. Mesa-Arango, A. C., Flórez-Muñoz, S. V., & Sanclemente, G. (2017). Mechanisms of skin aging. Latreia, 30(2), 160-170.
• 49. Musarra Pizzo, M., Pennisi, R., Ben Amor, I., Mandalari, G., & Sciortino, M. T. (2021). Antiviral activity exerted by natural products against human viruses. Viruses, 13(5), 828. https://doi.org/https://doi.org/10.3390/v13050828
• 50. Nielsen, V. G. (2020). The anticoagulant effect of Apis mellifera phospholipase A 2 is inhibited by CORM-2 via a carbon monoxide-independent mechanism. Journal of thrombosis and thrombolysis, 49(1), 100-107. https://doi.org/10.1007/s11239-019-01980-0
• 51. Nipate, S., Hurali, P. B., & Ghaisas, M. (2015). Evaluation of anti-inflammatory, anti-nociceptive, and anti-arthritic activities of Indian Apis dorsata bee venom in experimental animals: Biochemical, histological, and radiological assessment. Immunopharmacology and Immunotoxicology, 37(2), 171-184. https://doi.org/10.3109/08923973.2015.1009996
• 52. Park, M. H., Choi, M. S., Kwak, D. H., Oh, K. W., Yoon, D. Y., Han, S. B., Song, H. S., Song, M. J., & Hong, J. T. (2011). Anti‐cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF‐κB. The Prostate, 71(8), 801-812. https://doi.org/10.1002/pros.21296
• 53. Park, S., Erdogan, S., Hwang, D., Hwang, S., Han, E. H., & Lim, Y.-H. (2016). Bee venom promotes hair growth in association with inhibiting 5α-reductase expression. Biological and Pharmaceutical Bulletin, b16-00158. https://doi.org/10.1248/bpb.b16-00158
• 54. Patterson, R. A., & Stankewicz, H. A. (2021). Penicillin allergy. In StatPearls [Internet]. StatPearls Publishing.
• 55. Picoli, T., Peter, C. M., Vargas, G. D., Hübner, S. O., Lima, M. d., & Fischer, G. (2018). Antiviral and virucidal potential of melittin and apamin against bovine herpesvirus type 1 and bovine viral diarrhea virus. Pesquisa Veterinária Brasileira, 38, 595-604. https://doi.org/10.1590/1678-5150-PVB-4758
• 56. Sarhan, M., El-Bitar, A. M., & Hotta, H. (2020). Potent virucidal activity of honeybee “Apis mellifera” venom against Hepatitis C Virus. Toxicon, 188, 55-64. https://doi.org/10.1016/j.toxicon.2020.10.014
• 57. Sen, S., Kar, M., Roy, A., & Chakraborti, A. S. (2005). Effect of nonenzymatic glycation on functional and structural properties of hemoglobin. Biophysical chemistry, 113(3), 289-298. https://doi.org/10.1016/j.bpc.2004.05.005
• 58. Seo, B. K., Han, K., Kwon, O., Jo, D. J., & Lee, J. H. (2017). Efficacy of bee venom acupuncture for chronic low back pain: a randomized, double-blinded, sham-controlled trial. Toxins, 9(11), 361. https://doi.org/10.3390/toxins9110361
• 59. Son, D. J., Lee, J. W., Lee, Y. H., Song, H. S., Lee, C. K., & Hong, J. T. (2007). Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacology & therapeutics, 115(2), 246-270. https://doi.org/10.1016/j.pharmthera.2007.04.004
• 60. Sung, S. H., Kim, J. W., Han, J. E., Shin, B. C., Park, J. K., & Lee, G. (2021). Animal venom for medical usage in pharmacopuncture in Korean medicine: Current status and clinical implication. Toxins, 13(2), 105. https://doi.org/10.3390/toxins13020105
• 61. Sung, S. H., & Lee, G. (2021). Bee Venom Acupuncture Effects on Pain and Its Mechanisms: An Updated Review. Toxins, 13(9), 608. https://doi.org/10.3390/toxins13090608
• 62. Wehbe, R., Frangieh, J., Rima, M., El Obeid, D., Sabatier, J. M., & Fajloun, Z. (2019). Bee venom: Overview of main compounds and bioactivities for therapeutic interests. Molecules, 24(16), 2997. https://doi.org/10.3390/molecules24162997
• 63. Yang, E. J., Jiang, J. H., Lee, S. M., Yang, S. C., Hwang, H. S., Lee, M. S., & Choi, S.-M. (2010). Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models. Journal of neuroinflammation, 7(1), 1-12. https://doi.org/10.1186/1742-2094-7-69
• 64. Yang, W., Hu, F. l., & Xu, X. f. (2020). Bee venom and SARS-CoV-2. Toxicon, 181, 69. https://doi.org/10.1016/j.toxicon.2020.04.105
• 65. Yasin, B., Pang, M., Turner, J., Cho, Y., Dinh, N., Waring, A., Lehrer, R., & Wagar, E. (2000). Evaluation of the inactivation of infectious Herpes simplex virus by host-defense peptides. European Journal of Clinical Microbiology and Infectious Diseases, 19(3), 187-194. https://doi.org/10.1007/s100960050457
• 66. Yong, W. H., Wyman, S., & Levy, J. A. (1990). Optimal conditions for synthesizing complementary DNA in the HIV-1 endogenous reverse transcriptase reaction. AIDS 4(3), 199-206. https://doi.org/10.1097/00002030-199003000-00004
• 67. Zhang, J., Shi, D., Wang, L., Liu, R., & Zhang, L. (1995). Investigation of anaphylaxis by bee sting acupuncture in 9 case. Shanghai Journal of Acupuncture and Moxibustion, 3, 126.