Bee venom: A medical perspective

Yıl 2019, Cilt: 10 Sayı: 3, 414 - 421, 30.09.2019

Ali Korhan Sig , Mustafa Güney Özlem Öz Sig Hüseyin Şan

https://doi.org/10.18663/tjcl.451586

Cited By: 5

Öz

Apitherapy
is a complementary medical technique that has an old history and is applied in
various diseases worldwide. Apitherapeutical applications are not treatment
methods by themself, but theycan be substantial parts of multidisciplinary
approaches. One of them, bee venom therapy, is a currently-applied method
worldwide. Bee venom (BV) includes several substances such as peptides, phospholipids,
bioactive amines, amino acids, sugars, pheromones, enzymes and minerals.Studies
on whole BV and its singular components indicated that they have a huge
potential in anti-inflammatory, anti-arthritis, anti-nociceptive,
neuroprotective, anti-tumoral, anti-microbial, anti-diabetic and anti-rheumatic
activities.Results of in vivo studies
against arthritis, Parkinson’s and Alzheimer’s disease andcancer are very
promising, and also in vitro results
indicating other activities such as antimicrobial effect are observed. Although
mechanisms of action and many bioactive substances still remains unclear,
beneficial effects and potential utilities in certain medical conditions are
obvious. It seems bioactive components of BV may open new doors in treatment of
various diseases.

Anahtar Kelimeler

Apitherapy; Apitoxin; Bee Venom Therapy; Bee Venom Acupuncture

Arı zehri: Tıbbi bakış

Öz

Apiterapi,
dünya çapında çok sayıda hastalığın tedavisinde kullanılan ve kökeni çok eski
tıbbi kayıtlara dayanan bir tamamlayıcı tıp uygulamasıdır. Apiterapötik
teknikler kendi başlarına tedavi yöntemleri değil, aslında, çok disiplinli
tıbbi yaklaşımın bir parçasıdırlar. Bu yöntemlerden biri, arı zehri tedavisi,
dünyada şu anda uygulanan bir tekniktir. Arı zehri, peptitler, fosfolipitler,
biyoaktif aminler, amino asitler, şekerler, feromonlar, enzimler ve mineraller
gibi çok sayıda madde içermektedir. Arı zehrinin tümü ve içerdiği materyallere
ayrı ayrı yapılan çalışmalarda, bunların, antiinflamatuvar, antiartrit,
antinosiseptif, nöroprotektif, antitümöral, antimikrobiyal, antidiyabetik ve
antiromatizmal etki potantisiyeli açıkça gösterilmiştir. Artrit, Parkinson ve
Alzheimer hastalığı ile kansere yönelik in vivo çalışmalar ile antimikrobiyal
etkinlik gibi in vitro çalışmalarda son derece umut verici sonuçlar
gözlenmiştir. Her ne kadar etki mekanizması ve birçok biyoaktif içeriği henüz
aydınlatılmamış olsa da, belirli tıbbi durumlarda etkinliği açıkça görülmüştür.
Arı zehrinin biyoaktif komponentlerinin diğer başka hastalıklar için de yeni
kapılar açacağı düşünülmektedir.

Anahtar Kelimeler

Apiterapi; Apitoksin; Arı Zehri Tedavisi; Arı Zehri Akupunkturu

Kaynakça

• [1] Shimpi R, Chaudhari P, Deshmukh R, Devare S, Bagad Y, Bhurat MA. A review: pharmacotherapeutics of bee venom. World J Pharm Pharm Sci 2016; 5: 656-67.
• [2] Kim CMH. Apitherapy – Bee Venom Therapy. In: Grassberger M, Sherman RA, Gileva OS, Kim CMH, Mumcuoglu KY (eds). Biotherapy-history, principles and practice: A practical guide to the diagnosis and treatment of disease using living organisms. Springer Science & Business Media, Amsterdam 2013; 77-112.
• [3] Lee JD, Park HJ, Chae Y, Lim S. An overview of bee venom acupuncture in the treatment of arthritis. Evid Based Complement Alternat Med 2005; 2:79-84.
• [4] Lee MS, Pittler MH, Shin BC, Kong JC, Ernst E. Bee venom acupuncture for musculoskeletal pain: a review. J Pain 2008; 9:289-97.
• [5] Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther 2007; 115: 246-70.
• [6] Behroozi J, Divsalar A, Saboury AA. Honey bee venom decreases the complications of diabetes by preventing hemoglobin glycation. J Mol Liq 2014; 199: 371-75.
• [7] Oršolić N. Bee venom in cancer therapy. Cancer Metastasis Rev 2012; 31: 173-94.
• [8] Chang YH, Bliven ML. Anti-arthritic effect of bee venom. Agents Actions 1979; 9: 205-11.
• [9] Raghuraman H, Chattopadhyay A. Melittin: a membrane-active peptide with diverse functions. Biosci Rep 2007; 27: 189-223.
• [10] Gajski G, Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties. Environ Toxicol Pharmacol 2013; 36: 697-705.
• [11] Alvarez-Fischer D, Noelker C, Vulinović F et al. Bee venom and its component apamin as neuroprotective agents in a Parkinson disease mouse model. PloS One 2013; 8: 61700.
• [12] Yang EJ, Kim SH, Yang SC, Lee SM, Choi SM. Melittin restores proteasome function in an animal model of ALS. J Neuroinflammation 2011; 8: 69.
• [13] Cornara L, Biagi M, Xiao J, Burlando B. Therapeutic properties of bioactive compounds from different honeybee products. Front Pharmacol 2017; 8: 412.
• [14] Rady I, Siddiqui IA, Rady M, Mukhtar H. Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy. Cancer Lett 2017; DOI:10.1016/j.canlet.2017.05.010.
• [15] Hu H, Chen D, Li Y, Zhang X. Effect of polypeptides in bee venom on growth inhibition and apoptosis induction of the human hepatoma cell line SMMC‐7721 in‐vitro and Balb/c nude mice in‐vivo. J Pharm Pharmacol 2006; 58: 83-89.
• [16] Yang ZL, Ke YQ, Xu RX, Peng P. Melittin inhibits proliferation and induces apoptosis of malignant human glioma cells. Nan Fang Yi Ke Da Xue Xue Bao 2007; 27: 1775-77.
• [17] Park JH, Jeong YJ, Park KK et al. Melittin suppresses PMA-induced tumor cell invasion by inhibiting NF-κB and AP-1-dependent MMP-9 expression. Mol Cell 2010; 29: 209-15.
• [18] Park MH, Choi MS, Kwak DH, et al. Anti‐cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF‐κB. Prostate 2011; 71: 801-12.
• [19] Jo M, Park MH, Kollipara PS et al. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol Appl Pharmacol 2012; 258: 72-81.
• [20] Wang J, Li F, Tan J et al. Melittin inhibits the invasion of MCF‑7 cells by downregulating CD147 and MMP‑9 expression. Oncol Lett 2017; 13: 599-604.
• [21] Lee C, Choi D, Lee S, Sung-joo SB, Joo H, Bae H. Melittin suppresses tumor progression by regulating tumor-associated macrophages in a Lewis lung carcinoma mouse model. J Immunol 2017; DOI: 10.18632/oncotarget.18627
• [22] Zhang SF, Chen Z. Melittin exerts an antitumor effect on non‑small cell lung cancer cells. Mol Med Rep 2017; 16: 3581-86.
• [23] Zhang Z, Zhang H, Peng T, Li D, Xu J. Melittin suppresses cathepsin S-induced invasion and angiogenesis via blocking of the VEGF-A/VEGFR-2/MEK1/ERK1/2 pathway in human hepatocellular carcinoma. Oncol Lett 2016; 11: 610-18.
• [24] Wang D, Hu L, Su M, Wang J, Xu T. Preparation and functional characterization of human vascular endothelial growth factor-melittin fusion protein with analysis of the antitumor activity in vitro and in vivo. Int J Oncol 2015; 47: 1160-68.
• [25] Wang X, Xie J, Lu X et al. Melittin inhibits tumor growth and decreases resistance to gemcitabine by downregulating cholesterol pathway gene CLU in pancreatic ductal adenocarcinoma. Cancer Lett 2017; 399: 1-9.
• [26] Jin H, Zhao G, Hu J et al. Melittin-Containing Hybrid Peptide Hydrogels for Enhanced Photothermal Therapy of Glioblastoma. ACS Appl Mater Interfaces 2017; DOI: 10.1021/acsami.7b06431
• [27] Sardar AH, Das P, Das P. Development of antimicrobial peptide based anti-leishmanial agents: current understandings and future perspective. In: Méndez-Vilas A (ed). The Battle Against Microbial Pathogens: Basic Science, Technological Advances and Educational Programs. Formatex Research Center, Badajoz 2015; 137-43.
• [28] Hurwitz I, Forshaw A, Yacisin K, Ramalho-Ortigao M, Satoskar A, Durvasula R. Paratransgenic Control of Leishmaniasis: New Developments. In: Satoskar A, Durvasula R (eds). Pathogenesis of Leishmaniasis. Springer Science & Business Media, New York 2014; 25-43.
• [29] Pereira AV, de Barros G, Pinto EG et al. Melittin induces in vitro death of Leishmania infantum by triggering the cellular innate immune response. J Venom Anim Toxins incl Trop Dis 2016; 22: 1.
• [30] Adade CM, Oliveira IR, Pais JA, Souto-Padrón T. Melittin peptide kills Trypanosoma cruzi parasites by inducing different cell death pathways. Toxicon 2013; 69: 227-39.
• [31] Wachinger M, Kleinschmidt A, Winder D, von Pechmann N, Ludvigsen A, Neumann M. Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression. J Gen Virol 1998; 79: 731-40.
• [32] Hood JL, Jallouk AP, Campbell N, Ratner L, Wickline SA. Cytolytic nanoparticles attenuate HIV-1 infectivity. Antivir Ther 2013; 18: 95-103.
• [33] Kawakami H, Goto SG, Murata K, et al. Isolation of biologically active peptides from the venom of Japanese carpenter bee, Xylocopa appendiculata. J Venom Anim Toxins Incl Trop Dis 2017; 23: 29.
• [34] Kim WH, An HJ, Kim JY, et al. Apamin inhibits TNF-α-and IFN-γ-induced inflammatory cytokines and chemokines via suppressions of NF-κB signaling pathway and STAT in human keratinocytes. Pharmacol Rep 2017; DOI:10.1016/j.pharep.2017.04.006
• [35] Kim JY, An HJ, Kim WH, Park YY, Park KD, Park KK. Apamin suppresses biliary fibrosis and activation of hepatic stellate cells. Int J Mol Med 2017; 39: 1188-94.
• [36] Lee G, Bae H. Bee venom phospholipase A2: Yesterday’s enemy becomes today’s friend. Toxins 2016; 8: 48.
• [37] Bae H, Baek H, Shin D, Hwang DS. Bee venom phospholipase A2 (bvPLA2) protects against LPS-induced abortion. J Immunol 2017; 198: 220.7 (abstract)
• [38] Jung KH, Baek H, Kang M, Kim N, Lee SY, Bae H. Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice. Toxins 2017; 9: 68.
• [39] Fratini F, Cilia G, Turchi B, Felicioli A. Insects, arachnids and centipedes venom: a powerful weapon against bacteria. A literature review. Toxicon 2017; DOI:10.1016/j.toxicon.2017.02.020.
• [40] Perumal SR, Stiles BG, Franco OL, Sethi G, Lim LH. Animal Venoms as a Source of Natural Antimicrobials: An overview. Biochem Pharmacol 2017; 134: 127-38.
• [41] Lee JD, Kim SY, Kim TW et al. Anti-inflammatory effect of bee venom on type II collagen-induced arthritis. Am J Chin Med 2004; 32: 361-67.
• [42] Park HJ, Lee SH, Son DJ et al. Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF‐κB through interaction with the p50 subunit. Arthritis Rheum 2004; 50: 3504-15.
• [43] Sin DC, Kang MS, Song HS. Synergistic Effects of Bee Venom and Natural Killer Cells on B16F10 Melanoma Cell Growth Inhibition through IL-4-mediated Apoptosis. Acupunct 2017; 34: 1-9.
• [44] Kwon YB, Lee JD, Lee HJ et al. Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses. Pain 2001; 90: 271-80.
• [45] Kwon YB, Ham TW, Kim HW et al. Water soluble fraction (< 10 kDa) from bee venom reduces visceral pain behavior through spinal α 2-adrenergic activity in mice. Pharmacol Biochem Behav 2005; 80:181-87.
• [46] Baek YH, Huh JE, Lee JD, Park DS. Antinociceptive effect and the mechanism of bee venom acupuncture (Apipuncture) on inflammatory pain in the rat model of collagen-induced arthritis: Mediation by α 2-adrenoceptors. Brain Res 2006; 1073: 305-10.
• [47] Huh JE, Seo BK, Lee JW et al. Analgesic Effects of Diluted Bee Venom Acupuncture Mediated by δ-Opioid and α2-Adrenergic Receptors in Osteoarthritic Rats. Altern Ther Health Med 2017; 23: 5473.
• [48] Kim W, Kim MJ, Go D, Min BI, Na HS, Kim SK. Combined effects of bee venom acupuncture and morphine on oxaliplatin-induced neuropathic pain in mice. Toxins 2016; 8: 33
• [49] Lee JH, Li DX, Yoon H et al. Serotonergic mechanism of the relieving effect of bee venom acupuncture on oxaliplatin-induced neuropathic cold allodynia in rats. BMC Complement Altern Med 2014; 14: 471.
• [50] Han SM, Kim JM, Park KK, Chang YC, Pak SC. Neuroprotective effects of melittin on hydrogen peroxide-induced apoptotic cell death in neuroblastoma SH-SY5Y cells. BMC Complement Altern Med 2014; 14: 286.
• [51] Doo AR, Kim ST, Kim SN et al. 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: 88-91.
• [52] Khalil WK, Assaf N, ElShebiney SA, Salem NA. Neuroprotective effects of bee venom acupuncture therapy against rotenone-induced oxidative stress and apoptosis. Neurochem Int 2015; 80: 79-86.
• [53] Chung ES, Kim H, Lee G, Park S, Kim H, Bae H. Neuro-protective effects of bee venom by suppression of neuroinflammatory responses in a mouse model of Parkinson’s disease: role of regulatory T cells. Brain Behav Immun 2012; 26: 1322-30.
• [54] Han S, Lee K, Yeo J et al. Effect of honey bee venom on microglial cells nitric oxide and tumor necrosis factor-α production stimulated by LPS. J Ethnopharmacol 2007; 111: 176-81.
• [55]Daghestani MH, Selim ME, Abd-Elhakim YM et al. The role of apitoxin in alleviating propionic acid-induced neurobehavioral impairments in rat pups: The expression pattern of Reelin gene. Biomed Pharmacother 2017; 93: 48-56.
• [56] Wesselius T, Heersema DJ, Mostert JP et al. A randomized crossover study of bee sting therapy for multiple sclerosis. Neurology 2005; 65: 1764-68.
• [57] Fennell JF, Shipman WH, Cole LJ. Antibacterial action of melittin, a polypeptide from bee venom. Proc Soc Exp Biol Med 1968; 127: 707-10.
• [58] Cao Y, Yu RQ, Liu Y et al. Design, recombinant expression, and antibacterial activity of the cecropins–melittin hybrid antimicrobial peptides. Curr Microbiol 2010; 61: 169-75.
• [59] Hossen MS, Gan SH, Khalil MI. Melittin, a Potential Natural Toxin of Crude Bee Venom: Probable Future Arsenal in the Treatment of Diabetes Mellitus. J Chem 2017; DOI: doi.org/10.1155/2017/4035626
• [60] Garraud O, Hozzein WN, Badr G. Wound healing: time to look for intelligent,‘natural’immunological approaches? BMC Immunol 2017; 18: 23.
• [61] Lee J, Park J, Yeom J, Han EH, Lim YH. Inhibitory effect of bee venom on blood coagulation via anti-serine protease activity. J Asia Pac Entomol 2017; 20: 599-604.
• [62] Gauldie J, Hanson JM, Shipolini RA, Vernon CA. The structures of some peptides from bee venom. FEBS J 1978; 83: 405-10.
• [63] Junior RSF, Sciani JM, Marques-Porto R, et al. Africanized honey bee (Apis mellifera) venom profiling: Seasonal variation of melittin and phospholipase A2 levels. Toxicon 2010; 56: 355-62.
• [64] Owen MD, Sloley BD.5-Hydroxytryptamine in the venom of the honey bee (Apis mellifera L.): variation with season and with insect age. Toxicon 1988; 26: 577-81.
• [65] Abdulsalam MA, Ebrahim BE, Abdulsalam AJ. Immune thrombocytopenia after bee venom therapy: a case report. BMC Complement Altern Med 2016; 16: 107.
• [66] Wu Y, Han MF, Liu C et al. Design, synthesis, and antiproliferative activities of stapled melittin peptides. RSC Adv 2017; 7: 17514-18.