Honeybees, one of the most abundant and effective pollinator species, play a pivotal role in global food production. A third of the food we consume is produced directly or indirectly thanks to the diligent work of honeybees.
Beyond their role in agriculture, honeybees also offer an array of beneficial products. This article explores the multifaceted world of apitherapy, focusing on bee venom therapy and its potential applications in both human and veterinary medicine.
The Buzz about Apitherapy
Apitherapy is a comprehensive term used to describe a group of therapeutic and preventative procedures that utilize various bee products to improve health in both humans and animals. The use of bee products in apitherapy spans across multiple fields, including nutrition, food sciences, and pharmacology. Products like honey, pollen, and royal jelly are known for their medicinal and nutritional benefits, which range from desensitization and anti-inflammatory therapies to treatments for autoimmune diseases.
In recent years, the medicinal and nutritional properties of hive products have been studied extensively. The rise of drug resistance has necessitated the search for novel pharmacologically active substances, making bee products an appealing avenue for research. Additionally, in regions where conventional drug expenses are prohibitive, apitherapy provides a cost-effective alternative. This has led to the use of apitherapy as a supplemental medication in various countries, including Brazil, China, and Japan. However, despite its popularity, there is no shared consensus on the medical application of apitherapy.
Challenges and Considerations in Apitherapy
The effectiveness of apitherapy can vary due to the diverse methods of administration and use of hive products. Understanding the unique physiological reactions of humans and animals, along with factors such as age and weight, is crucial. Furthermore, bee products are complex mixtures with many unknown components, presenting a challenge for standardization. The therapeutic effects of bee products can fluctuate based on various factors, including soil, climate, harvesting and storage practices, and botanical sources.
To maximize the benefits of apitherapy and protect patients from potential hazards, it is essential to have a comprehensive understanding of the conditions under which bee products are produced. Standardizing these products could be a promising path for the future.
Bee Products in Apitherapy
A wide array of bee products are used in apitherapy, each offering unique benefits. These products include honey, propolis, pollen, bee bread, royal jelly, apilarnil, beeswax, and bee venom. Bee venom, in particular, has a long history of medicinal use.
Historical Use of Bee Venom
Bee venom has been utilized in traditional Eastern medicine for thousands of years to treat inflammatory illnesses. Ancient civilizations like Nibia, Babylon, and Assyria were likely acquainted with its properties. The Greek physician Hippocrates, often referred to as the “father of medicine,” used bee venom to treat arthritis and other inflammatory conditions. Even Pliny the Elder, a prominent Roman naturalist, mentioned bee venom in his work “Naturalis Historia.” Charlemagne, the Holy Roman Emperor, is believed to have used bee venom to treat his gout.
Modern Application of Bee Venom
The 19th century marked the first attempts to collect bee venom without harming the bee. The methods of collection evolved over the years, eventually leading to more humane techniques. Dr. Bodog Beck, a Hungarian-American, pioneered bee venom therapy and published the influential book “Bee Venom Therapy” in 1930. Dr. Joseph Broadman of New York began using bee therapy to treat arthritis in the 1950s and wrote about his experiences in the 1962 book “Bee Venom, the Natural Curative for Arthritis and Rheumatism.” Since then, many nations in Europe, Asia, and America have embraced bee venom therapy.
Medical Applications of Bee Venom
Traditionally, bee venom was used to treat inflammatory diseases like rheumatism. However, its applications have expanded to include the treatment of neurological disorders, asthma, and even infectious diseases like malaria. While there is limited research on the use of bee venom in veterinary medicine, numerous studies have addressed its potential applications in human medicine.
Bee venom, a potent substance with a rich history of therapeutic potential, is primarily produced by the venom gland located in the abdominal cavity of female honeybees. This gland is an essential component of the bee’s defense mechanism, allowing them to protect their colony. The use of their stinger and venom is particularly crucial in various scenarios within the hive’s social structure.
Defensive Roles of Bee Venom
The veliniferous apparatus of social insects in the genus Apis, which includes honeybees, serves as their primary defense mechanism. Bees utilize their stingers primarily for colony defense. When a perceived threat, such as an intruder or predator, approaches the hive, bees may sting in a coordinated effort to fend off the intruder and safeguard the colony. This is especially true for worker bees, which play a vital role in protecting the hive from potential threats.
Interestingly, the queen bee also possesses a stinger, although her role in stinging differs. The queen’s primary use of her stinger is to eliminate rival queens within the hive. In a honeybee colony, only one queen can reign at a time. When multiple queens are born simultaneously, various scenarios may unfold. Some queens may leave the hive with a group of worker bees, while others may engage in a battle for dominance. Additionally, a newly emerged queen may kill her rivals while they are still within their cells.
Age-Dependent Changes in Venom Composition
The composition of bee venom undergoes significant changes over the lifespan of a female honeybee. For instance, the protein concentration of queen bee venom is highest in the first three days of life, after which it diminishes. This initial burst of protein production is essential for the queen to assert her dominance and eliminate potential rival queens. As the bee’s venom gland degenerates, the protein content in honeybees decreases over time, with older bees producing less venom than their younger counterparts.
Moreover, bee venom is not detectable in female honeybees at the time of emergence but increases rapidly over the following two days. This level remains constant for the first 14 days and then gradually decreases. The venom’s composition also changes with age. For example, melittin, a key component of bee venom, is initially released in an inactive precursor form. It becomes active as the bee matures and transitions into the guardian stage, which typically occurs around day 20 of its life.
Stinging Mechanism and Venom Delivery
Honeybees possess a pointed stinger, which is extracted from their abdomen during a stinging event, along with the venom sac. However, unlike wasps and hornets, honeybees can only sting once before dying. When a bee stings a person or a mammal, the stinger remains embedded in the skin. Tragically, the act of stinging results in the bee’s death, as it forcefully rips out a portion of its intestines, muscles, and nerve center in its attempt to detach. The severity of this self-sacrifice lies in the fact that a significant portion of the bee’s body is lost during this process.
The stinger’s pointed end is equipped with tiny hooks that prevent it from being removed without causing damage. Once embedded in the skin, the bee employs a piston mechanism to push the venom into the wound. This action is rapid and usually expels the contents of the venom sac within minutes. Furthermore, bee venom contains an alarm pheromone, composed of the 2-heptanone molecule from the mandibular gland, which triggers other bees to join the defense of the hive.
Varied Reactions to Bee Venom
The effects of bee venom on humans can range from localized inflammation, which includes symptoms such as pain, heat, and itching, to systemic allergic reactions that may culminate in anaphylactic shock and, in severe cases of hypersensitivity, can even be fatal. This range of responses is commonly associated with bee stings in popular culture, but bee venom holds remarkable potential as a therapeutic agent when administered in small, controlled doses. The complex composition of bee venom, comprising a variety of chemicals with significant pharmacological and biochemical activities, makes it an intriguing subject of study.
Freshly secreted bee venom is a clear, colorless liquid that forms a light yellow powder upon drying. It carries the distinctive aroma of honey and is mildly acidic, with a pH ranging between 4.5 and 5.5. Bee venom’s water content varies between 55 and 70 percent, and its active components include peptides, proteins, enzymes, low molecular weight substances, and aliphatic constituents in varying quantities. Proteins make up a significant portion of bee venom, accounting for about 80% of its composition, with some being high molecular weight proteins and others peptides. Additionally, bee venom contains important low-molecular-weight substances, including biogenic amines.
In particular, some well-studied peptides in bee venom, such as adolapine, melittin, apamin, and peptide 401, have demonstrated various pharmacological activities. The complex composition of bee venom offers an exciting avenue for research and exploration, both in understanding its role in the bee colony and in uncovering its potential therapeutic applications.
Table 1: Composition of Bee Venom
Composition of bee venom: dry matter data according to Dotimas and Hider (1987
|Mast cell degranulating Peptide||1–2||Sugar (glucose, fructose)||2|
|Secapine||0.5||Aminobutyric acid and|
|Tertiapine, apamin, procamine||2–5||Volatile substances (pheromones)||4–8|
|Other small peptides||13–15||Mineral substances||3–4|
Venom Constituents and Their Biological Activities
Bee venom is a complex mixture of various bioactive compounds, each with its unique structure and function. This chapter explores some of the key constituents of bee venom and their biological activities.
Melittin, the most abundant element in bee venom, makes up approximately 50% of the peptides in the venom and, consequently, 50% of the dry bee venom. This peptide was first sequenced in 1967, revealing its 26 amino acid residues.
Melittin’s unique structure includes a hydrophilic carboxy-terminal region (residues 21-26) and a hydrophobic amino-terminal region (residues 1-20). This amphoteric nature allows melittin to be soluble in water as both a monomer and a tetramer. Its amphipathic α-helical structure enables it to spontaneously integrate into the phospholipid bilayer of cell membranes, causing damage. This action is reminiscent of a detergent-type molecule. Melittin is monomeric at lower concentrations necessary for cell lysis and tetrameric at higher concentrations in the bee venom sac.
Two distinct models describe the process of membrane permeation by amphipathic α-helical lytic peptides: the “barrel-stave” model and the “carpet” model. These models differ in the precise steps involved in membrane permeation. Melittin’s cytotoxic and anti-inflammatory actions, particularly on tumor cells, may be significantly influenced by these structural characteristics. Additionally, melittin can activate phospholipase A2 and adenylate cyclase, facilitating enhanced Ca2+ ion influx.
Melittin’s diverse pharmacological activities include anti-cancer, anti-inflammatory, antiviral, antibacterial, and neuroprotective properties.
Apamin is a polypeptide comprising 18 amino acids and containing two disulfide bridges. This neurotoxin is the smallest in bee venom and makes up less than 2% of the dry venom’s weight. Apamin functions as an allosteric inhibitor and selectively blocks small-conductance Ca2+-activated K+ (SK) channels.
SK channels are crucial for maintaining the ionic balance in cell membranes, regulating resting and action potentials, and facilitating signal transmission in neurons and muscle contraction. Apamin exerts its neurotoxic effects by mediating long-term after-hyperpolarization in neurons and muscle cells. Additionally, apamin can cross the blood-brain barrier and impact the central nervous system’s functioning. In animal studies, it has been shown to induce hyperactivity and convulsions.
Apamin also influences cell membrane permeability to potassium ions (K+) by inhibiting calcium-activated K+ channels. This has potential implications for the treatment of atherosclerosis and various pathophysiological conditions such as Parkinson’s disease.
Mast Cell Degranulation Peptide
Also known as “peptide 401,” this polypeptide consists of 22 amino acid residues and resembles apamin with two disulfide bridges. It comprises a small portion of bee venom, approximately 2-3% of the dry matter volume. Peptide 401 promotes mast cell degranulation, initiating inflammatory responses and significantly lowering blood pressure in animal trials. This component is thought to be responsible for the observed hypotension in bee venom intoxication.
Adolapin is a polypeptide composed of 103 amino acids, making up approximately 1% of dry bee venom. It exerts anti-inflammatory, analgesic, antinociceptive, and antipyretic effects by inhibiting prostaglandin synthesis and cyclooxygenase activity. The analgesic effect of adolapin may involve central mechanisms, as indicated by its partial suppression by naloxone. Adolapin also demonstrates antipyretic actions, likely through the inhibition of cerebral prostaglandin synthesis.
Phospholipase A2, the most prevalent enzyme in bee venom, constitutes 12-15% of the dry bee venom. This alkaline component has four disulfide bridges and 128 amino acid residues. Phospholipase A2 is highly aggressive against cell membranes, resulting in cytolysis. When acting in conjunction with melittin, it causes breaches in the cell membrane, enabling melittin to enter and dissolve the phospholipid layers.
Phospholipase A2 is the most allergenic and toxic element in bee venom and plays a critical role in the inflammatory cascade by hydrolyzing glycerophospholipids and releasing arachidonic acid. The enzyme is associated with anti-inflammatory, anti-tumor, and anti-parasitic properties.
Hyaluronidase is a polypeptide with 350 amino acid residues, constituting 1-2% of bee venom. It shares a 30% sequence identity with human hyaluronidase, which is involved in hyaluronic acid turnover. Bee venom hyaluronidase acts as an adjuvant for venom diffusion by breaking down glycolide linkages in acidic mucopolysaccharides found in connective tissues. This reduces tissue viscosity, allowing venom to enter the tissues. Additionally, the hydrolyzed hyaluronic acid particles possess pro-inflammatory, pro-angiogenic, and immune-stimulating properties. Hyaluronidase promotes blood vessel dilation and increased permeability, enhancing bee venom circulation.
In the following chapters, we will further explore the therapeutic potential of these bee venom constituents and their applications in human and veterinary medicine.
The Table 2 below summarizes the key characteristics of the bee venom’s constituent parts and the associated biological effects.
Table 2 – Biological effects of bee venom and its components.
|Melittin||Peptide with biological activity. Melittin prevents blood from clotting, works well against germs, shields against radiation. Melittin works as an anti-inflammatory in small dosages. It has a haemolytic action and is clearly cytotoxic.|
|Phospholipase A2||Phospholipase is the most important allergen and therefore the most harmful component of bee venom.|
|Hyaluronidase||It is an enzyme that allows venom to enter tissues and causes blood vessels to widen and tissues to become more permeable, increasing blood flow.|
|Apamin||Biologically active peptide; a neurotoxin.|
|Mast cell degranulating peptide||Peptide that degranulates mast cells by releasing biogenic amines.|
|Protease inhibitor||It has anti-inflammatory and hemorrhagic properties and inhibits the action of various proteases, including trypsin, chymotrypsin, plasmin, and thrombin.|
|Adolapin||Anti-inflammatory, anti-rheumatic, and analgesic.|
|Histamine||It dilates blood vessels and increases capillary permeability. It is an allergen.|
|Dopamine, noradrenaline||Neurotransmitters that affect the behaviour and physiology of the senses.|
|Alarm pheromone||It puts the colony on high alert.|
Effects and Applications in Veterinary Medicine
Bee venom, a product that has undergone extensive research in the fields of biology and medicine, is not only used in human apitherapy but also finds applications in veterinary medicine. Over the past two decades, numerous studies have employed animal models, particularly murine models, to investigate the effects and applications of bee venom in veterinary care. This chapter explores the diverse biological effects of bee venom and its potential applications in the realm of veterinary medicine.
Multifaceted Biological Effects
Bee venom exhibits a wide range of biological effects, some of which may appear contradictory. Understanding the specific components of bee venom that produce particular biological effects is crucial. Like many medications, bee venom has both intended therapeutic effects and potential adverse effects that need to be considered. Notably, crude bee venom is substantially less toxic than the combined action of its individual components. Toxic effects typically occur when the dose administered is significantly higher than the therapeutic dose, with bee venom becoming toxic at doses 200-500 times higher and individual components at doses 20-50 times greater than recommended.
Global Availability of Bee Venom Therapies
Bee venom therapies are accessible across the world, with particular popularity in regions such as Asia, Eastern Europe, and South America. While bee venom has traditionally been used to treat musculoskeletal illnesses like arthritis and rheumatism, its therapeutic applications extend to more unconventional areas. For instance, recent studies have explored bee venom as a potential supplemental treatment for COVID-19, demonstrating the versatility and ongoing research into bee venom’s therapeutic potential.
Bee venom has shown antioxidant properties, which are essential for maintaining the health of animals. Antioxidants help neutralize harmful free radicals and reduce oxidative stress. In veterinary medicine, this may be relevant in various contexts, such as preventing cell damage, supporting the immune system, and promoting overall well-being.
Inflammation is a common concern in both human and animal health. Bee venom’s anti-inflammatory properties have the potential to alleviate inflammatory conditions in animals. This includes treating conditions like arthritis and other inflammatory diseases that affect pets and livestock.
Bee venom’s anti-pathogenic effects are of interest in veterinary medicine. It may have applications in addressing infectious diseases in animals. These properties could be harnessed to develop novel therapies or preventive measures against pathogens affecting livestock and pets.
The anti-carcinogenic properties of bee venom are a subject of ongoing research. Veterinary medicine often deals with cancer diagnoses in animals, and any potential treatments or therapies that can mitigate the progression of cancer are of great importance. Bee venom’s anti-carcinogenic potential may hold promise in this regard.
Neurological Disorders in Animals
Neurological disorders can affect animals, leading to a range of health issues. The potential of bee venom in resolving neurological disorders in veterinary medicine is an area of study. Researchers are exploring how bee venom and its components may positively impact the nervous system in animals.
In the next section, we will delve deeper into the specific research and findings related to bee venom’s antioxidant, anti-inflammatory, anti-pathogenic, and anti-carcinogenic activities aimed at addressing neurological disorders in animals. This evolving field of research highlights the potential benefits of bee venom in improving the health and well-being of animals, opening up new avenues for veterinary care.
Current Limits in Bee Venom Usage
While bee venom holds promise for various therapeutic applications, it is essential to consider potential side effects and allergic reactions associated with its complex composition. Safe practices and well-informed treatment strategies are crucial to maximize the benefits of bee venom while minimizing risks. This chapter delves into the current limitations and challenges in the use of bee venom.
Adverse Effects and Allergic Reactions
The use of bee venom can lead to adverse effects and allergic responses in some individuals. These side effects are primarily due to the composition of bee venom. A comprehensive literature review by Park et al. in 2015 summarized investigations on the usage of bee venom and its harmful effects. The analysis of 145 articles revealed that approximately 28.87% of patients receiving bee venom experienced negative side effects. These side effects included allergic and anaphylactic reactions.
Allergic reactions to bee venom can vary in severity, from mild local swelling and itching at the site of the sting to more severe symptoms such as hives, difficulty breathing, and anaphylactic shock. Notably, allergic reactions can be life-threatening in some cases, making it essential to identify potential allergic individuals before administering bee venom therapy.
Animal Poisoning and Side Effects
Bee stings can also pose risks to animals. Noble and Armstrong (1999) observed clinical signs such as lethargy, haematuria, ataxia, and convulsions in two dogs that had been poisoned by bee stings, with one of the dogs tragically succumbing to the venom’s effects. Nair et al. (2019) observed acute and delayed onset of haemolytic anaemia, echinocytosis, spherocytosis, thrombocytopenia, haemoglobinaemia, and haemoglobinuria following bee sting poisoning. High doses of bee venom (above 1 mg per kg) in dogs and cats were found to cause an immediate drop in blood pressure to irreversible shock levels, along with severe electrocardiogram (ECG) abnormalities.
Proposed Solutions and Areas for Improvement
In light of these limitations, there are several recommended solutions and research areas that can enhance the safety and effectiveness of bee venom usage:
Purification of Bee Venom: Purification of bee venom is a critical step in minimizing adverse reactions. Removing histamine and phospholipase A2 can reduce allergic responses while maintaining the essential anti-inflammatory properties of the venom.
Specialized Analogs: Research into the effects of individual bee venom components, such as melittin, can lead to the development of specialized analogs for therapeutic use. This research can help create analogs with specific actions and reduced cytotoxicity against normal cells.
Accurate Identification and Measurement: Accurate identification and measurement of bee venom components are essential for safe and effective use. This ensures that the substance being used is well-characterized.
Standardization: Standardizing bee venom production is necessary to ensure the reproducibility of outcomes and treatment safety.
Enhanced Delivery: Overcoming challenges related to the short plasma half-life of bee venom can be achieved by developing delivery methods that use polymers or nanoparticles. These methods can extend the time that bee venom remains active in the body.
Pathways in the Body: A deeper understanding of the pathways bee venom or its components follow in the body is essential to maximize their effectiveness and safety. This knowledge can help in optimizing treatment regimens.
Bee venom, with its multifaceted therapeutic potential, presents an exciting prospect for the treatment of a wide range of ailments. Its diverse properties, including antibacterial, antiviral, and anti-parasitic capacities, make it a compelling alternative to conventional drugs, offering the potential to combat drug resistance phenomena.
One of the significant advantages of bee venom therapy is its holistic approach, where its use for one condition can yield positive effects on concomitant diseases, as evidenced in this comprehensive exploration of its anti-inflammatory, anti-tumor, and other properties.
Nevertheless, the use of bee venom in clinical settings necessitates a cautious approach. Efficacy studies are essential to determine the optimal doses that achieve the desired pharmacological response while minimizing potential side effects. As in human medicine, the substantial body of in vitro research must be followed by clinical trials in veterinary medicine.
These trials will provide valuable insights into the safe and effective use of bee venom in veterinary clinical practice, ensuring that its potential benefits can be harnessed while safeguarding the health and well-being of animals.
opical products with bee venom are applied directly to the skin and are available in a variety of forms, including creams, gels, serums, and balms. Bee venom, also known as apitoxin, contains a variety of active components that have been shown to have anti-inflammatory, analgesic, and wound-healing properties.
Topical bee venom products are often used to treat a variety of conditions, including:
- Pain: Arthritis, muscle pain, joint pain, back pain, neuropathic pain
- Inflammation: Skin inflammation, such as eczema and psoriasis
- Wound healing: Cuts, scrapes, burns
- Skin aging: Fine lines and wrinkles, age spots
Some people also use topical bee venom products to improve their skin complexion and reduce the appearance of acne scars.
How to use topical bee venom products
Topical bee venom products are typically applied to the affected area two to three times per day. It is important to start with a small amount and gradually increase the amount as tolerated. Bee venom can cause a mild burning sensation, which is usually temporary.
If you have sensitive skin, it is important to patch test the product on a small area of skin before using it on a larger area.
Safety and side effects
Topical bee venom products are generally safe for most people. However, some people may experience side effects, such as redness, itching, and swelling. In rare cases, people may experience an allergic reaction to bee venom.
It is important to talk to your doctor before using topical bee venom products, especially if you have any underlying medical conditions or are taking any medications.
Topical bee venom products on the market
There are a variety of topical bee venom products on the market. Some popular brands include:
- Apixin Bee Venom Cream
- Bee Venom Cream – Lacrème Beauté
- Bee Venom Cream – Naturswiss
- Dragon Honor New Zealand Bee Venom Cream
- Casiab Bee Venom Pain and Bone Healing Cream
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965945/