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​Honeybee Venom Therapy

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Honeybees are truly miraculous creatures, and in addition to being all-important pollinators they manufacture several health-giving products (apitherapy), such as honey, propolis, bee pollen, and bee wax. Lesser known is the medicinal use of honeybee venom therapy (BVT) that has been practiced cross-culturally for centuries. BVT, the use of live bee stings (or injectable bee venom), has been used more than 2000 years in treating numerous types of acute and chronic afflictions. BVT was practiced in ancient Egypt, Greece, and China — three Great Civilizations are known for their highly developed medical systems. Hippocrates recognized the healing virtues of honeybee venom for treating arthritis and other joint problems. Throughout the world, physicians are now using BVT with success in the treatment of arthritis, multiple sclerosis, Lyme disease, autoimmune diseases, psoriasis, epilepsy, asthma, and even certain types of cancer. The world scientific literature contains more than 1500 articles on the medicinal value of BVT.

 

Honeybee venom is a complex mixture of chemicals, including peptides and enzymes, which have strong beneficial neurological, immunological, and anti-inflammatory effects. Honeybee venom contains more than 18 active components, of which mellitin (40-50%) is the main active peptide that exhibits anti-inflammatory, antibacterial, antiviral, and anti-carcinogenic properties. Other therapeutic bee venom chemicals are Adolapin and Apamin. Adolapin acts as an anti-inflammatory and analgesic, whereas Apamin helps to increase cortisol production in the adrenal gland.  

 

Administering Honeybee Venom

 

Traditionally, honeybee venom has been administered with live bees by stimulating them to sting in the affected area or in traditional Chinese medicine administered on a specific acupuncture point. Current day variety of honeybee venom products includes injectable liquid venom, creams, ointments, and oral homeopathic preparations. Practitioners may choose the most suitable application for the condition being treated owing to the individual characteristics of the patient.

Next to the effect of a live honeybee, injectable venom solution is a standard method to administer BVT. The injectable venom solution is prepared from pure honeybee venom. The solution is administered just under the skin to imitate the effect of a bee sting. Another popular way of administering BVT is with topical creams and ointments applied to the affected body part. Before injection or administration of honeybee venom, it is essential to have epinephrine on hand in the rare case of an allergic reaction.

 

Collecting Honeybee Venom

Honeybee venom is synthesized in the venom glands of worker and queen bees and stored in their venom sacs. During the stinging process, it is expressed through the sting apparatus. The venom is commercially collected by means of electric shock stimulation. Bees come into contact with a collector frame that is covered with a wire grid and receive a mild electrical shock causing them to release their venom. The venom is then allowed to air dry and is then gathered and processed. Previous venom collection methods killed bees; however, bee venom collected by the electro-stimulant method does not harm the bee.

Reactions and Sensitivity

Honeybee venom reactions and sensitivity for most individuals, normally include some redness, swelling, and itching that usually resolves in a few hours. However, in the allergic individual, a more long-lasting and severe reaction may occur. Many individuals are allergic to a wasp, hornet, and yellow jacket stings, but few are allergic to honeybee venom. Because of their vegetarian nature honeybee venom is less toxic and chemically differs from their carnivorous cousins. It is estimated that honeybee stings account for less than 5% of all adverse stinging insect reactions. The risk of an anaphylactic allergic reaction to honeybee venom is rare, but real.

No official body in the US has sanctioned BVT as a recognized treatment modality. Bee venom has been approved by the FDA for de-sensitization purposes only. Thus, BVT is considered, from both the legal and medical viewpoint, an experimental approach. 

General Studies

 

Ali, M. A. A. S. M. "Studies on bee venom and its medical uses." Int J Adv Res Technol 1, no. 2 (2012): 69-83.

Son, Dong Ju, Jae Woong Lee, Young Hee Lee, Ho Sueb Song, Chong Kil Lee, and Jin Tae Hong. "Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds." Pharmacology & therapeutics 115, no. 2 (2007): 246-270.

 

Pharmacologic Studies 

Honeybee venom is a well-known pharmacologically active product of the hive, which is synthesized by the venom glands associated with the sting apparatus of worker and queens, stored in the venom reservoir, and injected through the sting apparatus during the stinging process. Due to its antioxidants, anti-coagulants, anti-inflammatory properties, and bioactive substances like melittin and phospholipase BV is mainly used to treat many inflammatory disorders such as arthritis, cancer, diseases of nervous system, heart and blood system abnormalities, skin diseases and others. Furthermore, therapeutic application of honeybee venom includes their use in the management of bursitis, tendonitis, dissolving scar tissue, in the management of postherpetic neuralgia, Lyme disease, rheumatoid arthritis, osteoarthritis, multiple sclerosis, and more.

Banks, B. E., Hanson, J. M., & Sinclair, N. M. (1976). The isolation and identification of noradrenaline and dopamine from the venom of the honey bee, Apis mellifica. Toxicon, 14(2), 117-125.

Banks, B. E., Christopher E. Dempsey, Charles A. Vernon, Jane A. Warner, and Jill Yamey. "Anti-inflammatory activity of bee venom peptide 401 (mast cell degranulating peptide) and compound 48/80 results from mast cell degranulation in vivo." British journal of pharmacology 99, no. 2 (1990): 350.

 

Banks, BARBARA EC, and RUDOLF A. Shipolini. "Chemistry and pharmacology of honey-bee venom." Venoms of the Hymenoptera: Biochemical, pharmacological and behavioural aspects (1986): 330-416.

Billingham,M.E.J.,  Morley,J.,  Hanson,J.M.,  Shipolini,R.A.,  Vernon,C.A. (1973)  –  Letter: An anti-inflammatory peptide from bee venom,
in Nature 245 (5421),  pp.163-164.

 

Gauldie, Jack, Jennifer M. Hanson, Franklin D. Rumjanek, Rudolf A. Shipolini, and Charles A. Vernon. "The peptide components of bee venom." European journal of biochemistry 61, no. 2 (1976): 369-376.

Hanson, Jennifer M., J. Morley, and C. Soria-Herrera. "Anti-inflammatory property of 401 (MCD-peptide), a peptide from the venom of the bee Apis mellifera (L.)." British journal of pharmacology 50, no. 3 (1974): 383.

Liu, Shujing, Mei Yu, Ying He, Lin Xiao, Fang Wang, Changcheng Song, Shuhan Sun, Changquan Ling, and Zhiheng Xu. "Melittin prevents liver cancer cell metastasis through inhibition of the Rac1‐dependent pathway." Hepatology 47, no. 6 (2008): 1964-1973.

Raghuraman, H., and Amitabha Chattopadhyay. "Melittin: a membrane-active peptide with diverse functions." Bioscience reports 27, no. 4-5 (2007): 189-223.

Shkenderov, Stefan, and Krasimira Koburova. "Adolapin-a newly isolated analgetic and anti-inflammatory polypeptide from bee venom." 

Toxicon 20, no. 1 (1982): 317-321.

Vick, James A., and William H. Shipman. "Effects of whole bee venom and its fractions (apamin and melittin) on plasma cortisol levels in the dog." 

Toxicon 10, no. 4 (1972): 377-380.

Antimicrobial Effects

Honeybee venom contains a complex mixture of therapeutic compounds, including antimicrobial peptides, allowing bees to defend their hives against predators and external threats. The melittin peptide, the predominant component of bee venom (40–48%, w/w), has been investigated substantially, and exhibits potent cytolytic and antimicrobial activities. Honeybee venom’s potential actions against parasites, bacteria, and viruses have been extensively examined and verified with minimal toxicity in vitro and in vivo. 

Adade, Camila M., Isabelle RS Oliveira, Joana AR Pais, and Thaïs Souto-Padrón. "Melittin peptide kills Trypanosoma cruzi parasites by inducing different cell death pathways." Toxicon 69 (2013): 227-239.

Choi, Ji Hae, A. Yeung Jang, Shunmei Lin, Sangyong Lim, Dongho Kim, Kyungho Park, Sang‑Mi Han, Joo‑Hong Yeo, and Ho Seong Seo. "Melittin, a honeybee venom‑derived antimicrobial peptide, may target methicillin‑resistant Staphylococcus aureus." 

Molecular medicine reports 12, no. 5 (2015): 6483-6490.

Dosler, Sibel, Elif Karaaslan, and A. Alev Gerceker. "Antibacterial and anti-biofilm activities of melittin and colistin, alone and in combination with antibiotics against Gram-negative bacteria." Journal of Chemotherapy 28, no. 2 (2016): 95-103.

Leandro, Luís F., Carlos A. Mendes, Luciana A. Casemiro, Adriana HC Vinholis, Wilson R. Cunha, Rosana de Almeida, and Carlos HG Martins. "Antimicrobial activity of apitoxin, melittin and phospholipase A2 of honey bee (Apis mellifera) venom against oral pathogens." Anais da Academia Brasileira de Ciências 87, no. 1 (2015): 147-155.

Perumal Samy, R., P. Gopalakrishnakone, M. M. Thwin, T. K. V. Chow, H. Bow, E. H. Yap, and T. W. J. Thong. "Antibacterial activity of snake, scorpion and bee venoms: a comparison with purified venom phospholipase A2 enzymes." Journal of applied microbiology 102, no. 3 (2007): 650-659.

Arthritis: Osteo and Rheumatoid

Honeybee venom has been shown to have anti-arthritis effects in several arthritis models. Melittin, a major peptide component of honeybee venom has anti-inflammatory and anti-arthritis properties, and its inhibitory activity on nuclear factor kappaB (NF-κB) may be essential for the effects of honeybee venom. The anti-nociceptive effects of honeybee venom have also been demonstrated in thermal, visceral, and inflammatory pain models. Acupoint stimulation (api-puncture) therapy into subcutaneous region has been shown to be an effective therapy in the honeybee venom-induced antinociceptive effects. Multiple mechanisms, such as activation of the central and spinal opioid receptor, and α2-adrenergic activity, as well as activation of the descending serotonergic pathway have been suggested. The inhibition of c-Fos expression in the spinal cord by honeybee venom api-puncture in several nociceptive models is also reported to be a possible mechanism.

 

Chang, Yi-Han, and Marcia L. Bliven. "Anti-arthritic effect of bee venom." Agents and actions 9, no. 2 (1979): 205-211.

Eiseman, Julie L., Jurgen Von Bredow, and Alvito P. Alvares. "Effect of honeybee (Apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat." 

Biochemical pharmacology 31, no. 6 (1982): 1139-1146.

Fisher, R. B. "Bee venom and chronic inflammatory disease." The New Zealand medical journal 99, no. 808 (1986): 639.

Kwon, Young Bae, Hye Jung Lee, Ho Jae Han, Woung Chon Mar, Sung Keel Kang, Ok Byung Yoon, Alvin J. Beitz, and Jang Hern Lee. "The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats." Life sciences 71, no. 2 (2002): 191-204.

Kwon, Young-bae, Jae-dong Lee, Hye-jung Lee, Ho-jae Han, Woung-chon Mar, Sung-keel Kang, Alvin J. Beitz, and Jang-hern Lee. "Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses." Pain 90, no. 3 (2001): 271-280.

Lee, Gihyun, and Hyunsu Bae. "Anti-inflammatory applications of melittin, a major component of bee venom: Detailed mechanism of action and adverse effects." Molecules 21, no. 5 (2016): 616.

Lee, Jae-Dong, Hi-Joon Park, Younbyoung Chae, and Sabina Lim. "An overview of bee venom acupuncture in the treatment of arthritis." Evidence-based complementary and alternative medicine 2 (2005).

Lee, Jae-Dong, Su-Young Kim, Tae-Woo Kim, Sang-Hoon Lee, Hyung-In Yang, Doo-Ik Lee, and Yun-Ho Lee. "Anti-inflammatory effect of bee venom on type II collagen-induced arthritis." The American journal of Chinese medicine 32, no. 03 (2004): 361-367.

Lee, Ju Ah, Mi Ju Son, Jiae Choi, Ji Hee Jun, Jong-In Kim, and Myeong Soo Lee. "Bee venom acupuncture for rheumatoid arthritis: a systematic review of randomised clinical trials." BMJ open 4, no. 11 (2014).

Lee, Myeong Soo, Max H. Pittler, Byung-Cheul Shin, Jae Cheol Kong, and Edzard Ernst. "Bee venom acupuncture for musculoskeletal pain: a review." The Journal of Pain 9, no. 4 (2008): 289-297.

Won, Choong-Hee, Seong-Sun Hong, Christopher MH Kim, Chong-Hee Won, Seung-Back Kang, D-Hoon Lee, Young-Do Ko, Bong-Soon Chang, and You-Young Lee. "Efficacy of apitox (bee venom) for osteoarthritis: A randomized active-controlled trial." Journal of the American Apitherapy Society 7, no. 3 (2000): 53-60.

Park, Hye Ji, Seong Ho Lee, Dong Ju Son, Ki Wan Oh, Ki Hyun Kim, Ho Sueb Song, Goon Joung Kim, Goo Taeg Oh, Do Young Yoon, and Jin Tae Hong. "Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF‐κB through interaction with the p50 subunit." Arthritis & rheumatism 50, no. 11 (2004): 3504-3515.

Zurier, R. B., H. Mitnick, D. Bloomgarden, and G. Weissmann. "Effect of bee venom on experimental arthritis." Annals of the rheumatic diseases 32, no. 5 (1973): 466.

Cancer 

Honeybee venom has been widely used in the treatment of some immune-related diseases, as well as in recent times in treatment of tumors. Apoptosis, necrosis, and lysis of tumor cells were suggested as possible mechanisms by which bee venom inhibited tumor growth. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, can be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the anti-cancer activity of honeybee venom. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is important for the melittin-induced anti-cancer effects.

 

Alizadehnohi, Masoumehzaman, Mohammad Nabiuni, Zahra Nazari, Zahra Safaeinejad, and Saeed Irian. "The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp." Journal of venom research 3 (2012): 22.

Amini, Elaheh, Javad Baharara, Najmeh Nikdel, and Farzaneh Salek Abdollahi. "Cytotoxic and Pro-Apoptotic Effects of Honey Bee Venom and Chrysin on Human Ovarian Cancer Cells." Asia Pacific Journal of Medical Toxicology 4, no. 2 (2015): 68-73.

Huh, Jeong-Eun, Yong-Hyeon Baek, Min-Ho Lee, Do-Young Choi, Dong-Suk Park, and Jae-Dong Lee. "Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice." Cancer letters 292, no. 1 (2010): 98-110.

Jang, Mi-Hyeon, Min-Chul Shin, Sabina Lim, Seung-Moo Han, Hi-Joon Park, Insop Shin, Ji-Suk Lee, Kyoung-Ah Kim, Ee-Hwa Kim, and Chang-Ju Kim. "Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299." Journal of pharmacological sciences 91, no. 2 (2003): 95-104.

 

Kim, Yong-Wan, Pankaj Kumar Chaturvedi, Sung Nam Chun, Yang Gu Lee, and Woong Shick Ahn. "Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line." Oncology reports 33, no. 4 (2015): 1675-1682.

 

Liu, Xing, Dawei Chen, Liping Xie, and Rongqing Zhang. "Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in‐vitro and growth of murine B16 melanomas in‐vivo." Journal of pharmacy and pharmacology 54, no. 8 (2002): 1083-1089.

 

Mahmoodzadeh, Amir, Hannaneh Zarrinnahad, Kamran Pooshang Bagheri, Ali Moradia, and Delavar Shahbazzadeh. "First report on the isolation of melittin from Iranian honey bee venom and evaluation of its toxicity on gastric cancer AGS cells." Journal of the Chinese Medical Association 78, no. 10 (2015): 574-583.

Oršolić, Nada, Lidija Šver, Srđan Verstovšek, Svjetlana Terzić, and Ivan Bašić. "Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom." Toxicon 41, no. 7 (2003): 861-870.

Rady, Islam, Imtiaz A. Siddiqui, Mohamad Rady, and Hasan Mukhtar. "Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy." 

Cancer letters 402 (2017): 16-31.

Russell, Pamela J., Dean Hewish, Teresa Carter, Katy Sterling-Levis, Kim Ow, Meghan Hattarki, Larissa Doughty et al. "Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies." Cancer Immunology, Immunotherapy 53, no. 5 (2004): 411-421.

Zarrinnahad, Hannaneh, Amir Mahmoodzadeh, Monireh Parviz Hamidi, Mehdi Mahdavi, Ali Moradi, Kamran Pooshang Bagheri, and Delavar Shahbazzadeh. "Apoptotic effect of melittin purified from Iranian honey bee venom on human cervical cancer hela cell line." International journal of peptide research and therapeutics 24, no. 4 (2018): 563-570.

 

Neurological Effects and Multiple Sclerosis

Recent clinical studies have demonstrated that honeybee venom and its derived active components are applicable to a wide range of neurodegenerative diseases, including multiple sclerosis and Parkinson’s disease. These effects of honeybee venom are known to be in part mediated by modulating immune cells in the periphery, and glial cells and neurons in the central nervous system. 

Chung, Eun Sook, Himchan Kim, Gihyun Lee, Soojin Park, Hyunseong Kim, and Hyunsu Bae. "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, behavior, and immunity 26, no. 8 (2012): 1322-1330.

 

Hwang, Deok-Sang, Sun Kwang Kim, and Hyunsu Bae. "Therapeutic effects of bee venom on immunological and neurological diseases." Toxins 7, no. 7 (2015): 2413-2421.

Karimi, Akbar, Farhad Ahmadi, Kazem Parivar, Mohammad Nabiuni, Saied Haghighi, Sohrab Imani, and Hossein Afrouzi. "Effect of honey bee venom on lewis rats with experimental allergic encephalomyelitis, a model for multiple sclerosis." 

Iranian journal of pharmaceutical research: IJPR 11, no. 2 (2012): 671.

Karimi, A., K. Parivar, M. Nabiuni, S. Haghighi, and S. Imani. "Effect of honey bee venom and vitamin B12 on gliosis of brain stem in rats with experimental allergic encephalomyelitis-animal model for multiple sclerosis." (2011): 37-45.

KIM, Hyun-Woo, Young-Bae KWON, Tae-Won HAM, Dae-Hyun ROH, Seo-Yeon YOON, Hye-Jung LEE, Ho-Jae HAN, Il-Suk YANG, Alvin J. Beitz, and Jang-Hern LEE. "Acupoint stimulation using bee venom attenuates formalin-induced pain behavior and spinal cord Fos expression in rats." Journal of veterinary medical science 65, no. 3 (2003): 349-355.

Psoriasis

Hegazi, Ahmed G., Fatma A. Abd Raboh, Nahla E. Ramzy, Dalia M. Shaaban, and Doha Y. Khader. "Bee venom and propolis as new treatment modality in patients with localized plaque psoriasis." International Research Journal of Medicine and Medical Sciences 1, no. 1 (2013): 27-33.

 

Radioprotective

 

Ginsberg, Nathan J., Maxwell Dauer, and KARL H. SLOTTA. "Melittin used as a protective agent against X-irradiation." Nature 220, no. 5174 (1968): 1334-1334.

Shipman, William H., and Leonard J. Cole. Increased radiation resistance of mice injected with bee venom one day prior to exposure. NAVAL RADIOLOGICAL DEFENSE LAB SAN FRANCISCO CA, 1966.

Varanda, E. A., and D. C. Tavares. "Radioprotection: mechanisms and radioprotective agents including honeybee venom." Journal of Venomous Animals and Toxins 4, no. 1 (1998): 5-21.

Reproductive Therapy

Ali, Ali Farid Mohamed, Baha Fateen, Ahmed Ezzet, Hoda Badawy, Asherf Ramadan, and Alaa El-tobge.

"Laparoscopic intraovarian injection of bee venom inthe treatment of polycystic ovarian disease: a new modality." Obstetrics & Gynecology 95, no. 4 (2000): S15.

Venom Collection

Benton, Allen W., Roger A. Morse, and Joseph D. Stewart. "Venom collection from honey bees." Science 142, no. 3589 (1963): 228-230.

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