The Rats Are Going To Love This Announcement, And We Will Too!

By Grace Bennett, Eliza Grimm, and Natalie Moore

While most people recognize that a bee’s stinger is an important defense mechanism for the bee, they don’t realize that the venom in a bee sting could be beneficial to humans in a medical setting due to its anti-inflammatory properties. While the general opinion of bees has grown increasingly positive in recent years, many people still fear getting stung by them. On the flip side, bee venom has been used as a medicinal tool throughout history, with the first evidence of it dating back to ancient Greece and Egypt. Characterized by swelling and tenderness in joints, Arthritis is a chronic illness that can cause acute joint pain and affects people across the world. Gouty arthritis is an even more severe form of arthritis in which there is sudden severe swelling around the joints due to a build up in uric acid, which crystallizes around the joints and causes the breakdown of cartilage.

In 2021, a team of researchers from Kyung Hee University in Seoul, South Korea tested bee venom’s ability to treat gout in rats to see if bee venom could be a viable alternative to synthetic anti-inflammatory drugs such as NSAIDs (ibuprofen, aspirin, etc.) and colchicine (an alternative treatment for gout in people unable to tolerate NSAIDs). Gout is a type of arthritis that causes redness, swelling, pain, and tenderness in one or more joints. While synthetic drugs treat inflammation from gout effectively, there are many negative side-effects associated with them which is why researchers want to find alternatives.

[1] Figure 1: shows the difference in lab rats ankles dependent upon injection with bee venom, colchicine, or nothing but MSU crystals

In their experiment, the researchers injected the ankles of adult male rats with MSU crystals to cause gout to develop. One group of rats were also injected with bee venom, another group was injected with colchicine, and the last group only received theMSU injection. They made observations hourly within the 24 hour period after the injections. First, they measured the circumference of the rats’ gouty ankles, and then they performed a von Frey test to measure the rats’ pain responses. In a von Frey test, researchers use tiny filaments to poke the hindpaws of rats and observe their responses to determine how much pain they are experiencing. When a rat shows no pain response, the researchers move on to a slightly thicker filament. The researchers then record the size of the filament that elicits a response.

When the researchers measured the rats’ ankles, they found that bee venom and colchicine treated rats showed a similar response. While the rats who were only injected with the MSU crystals continued to show a significant increase in swollenness after the first three hours, the swollenness of the bee venom and colchicine treated rats leveled off a little and started to decrease slightly after the six hour mark as shown in Figure 1.

[2] Figure 2: This graph shows the relationship between time after injection and the size of von Frey filaments that elicited a response from the rats.

The von Frey test also showed that bee venom was effective at treating the gout. The untreated rats had the most pain around the three hour mark, and after that it improved slightly before finally leveling off at the six hour mark. The colchicine treated rats showed a slight increase in pain at the three hour mark, had the most pain around the six hour mark, and went back to normal by the 24 hour mark. The entire time, their pain was significantly less than that of the untreated rats. Finally, the bee venom treated rats saw no increase in pain until the six hour mark, and went back to normal after the eight hour mark. The whole time, they had less pain than the colchicine treated rats, as seen in Figure 2.

These observations show that bee venom proved to be similarly effective to (or even more effective than) colchicine when it comes to treating inflammation from gout in rats. While this doesn’t prove that bee venom would be a viable treatment option for gout in humans, it does show promise. This can prove as an important scientific breakthrough for medical science and the eventual treatment of arthritis in humans. In the future, we may see more researchers conducting similar experiments in other mammals and eventually humans. In addition to the human benefit, the utilization of bee venom is beneficial to the bees themselves as it can encourage people to think about the many benefits provided by bees and thus further preservation of bee species worldwide. As proven by the Kyung Hee University researchers, this potential for partnership between bees and humans is a mutually beneficial relationship that can better the future of both man and insect.



Further Reading

Mayo Clinic . (2021). Arthritis - Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/arthritis/symptoms-causes/syc-20350772

Goo, B., Lee, J., Park, C., Yune, T., & Park, Y. (2021). Bee venom alleviated edema and pain in monosodium urate crystals-induced gouty arthritis in rat by inhibiting inflammation. Toxins, 13(9), 661. https://www.mdpi.com/2072-6651/13/9/661



Media Credits

[1] and [2] Figures from Goo et al. (2021) in Toxins CC BY 4.0 DEED.

Exploring the Buzz: Bee Venom Injections and Parkinson's Disease

By Emily Mikitka and Courtney Bean

Picture Parkinson's disease as a masterful puppeteer working discreetly behind the scenes of life's grand spectacle. The puppeteer's subtle influence, mirrored by the gradual depletion of dopamine-producing cells in the brain, results in a slow yet significant alteration in the rhythm and coordination of the body's movements. Similar to the graceful dance of a puppet, the nuances of everyday tasks transform into a formidable challenge for individuals contending with Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder that affects millions of people worldwide, impacting motor function and quality of life. The main symptoms of Parkinson's disease include tremors (uncontrollable shaking), bradykinesia (slowness of movement), rigidity (stiffness of the limbs and joints), and postural instability (difficulty maintaining balance). These symptoms typically develop gradually over a period of time and may vary in severity from person to person. In the search for innovative therapies, researchers are exploring unconventional avenues, including the potential benefits of bee venom. Bee venom is a complex mixture of proteins and peptides produced by bees, primarily used as a defense mechanism. Honeybees deploy this venom as a means of protection against predators. The bee venom is known to combat inflammation and potentially lessen the severity of painful symptoms. It’s often used in studies to treat nervous system disorders, like in this study, Parkinson’s Disease. Melittin is the predominant and biologically active component in bee venom. In a recent study, researchers delved into the effects of monthly bee venom injections on moderately affected Parkinson's disease patients. Andreas Hartman set out to find and determine whether 11 months of bee venom injections significantly improves patients’ symptoms, using scores on the United Parkinson’s Disease Rating Scale (UPDRS).

[1] A bee on a flower

The study included 40 Parkinson's disease patients at Hoehn & Yahr stages 1.5 to 3, randomly assigned to either monthly bee venom injections or equivalent volumes of saline (placebo). A placebo is a fake treatment that is commonly used in studies like this when researchers are attempting to prove whether their hypothesis is correct, that their treatment (bee venom in this case) is actually having an impact on treatment in comparison to the fake placebo treatment. Each group was anonymous, not knowing which supplement they were receiving based on them being disguised in two of the same syringe. Secondary objectives included evaluating the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to assess disease progression. Safety was also a priority, with monitoring for specific IgE against bee venom and skin tests when necessary. After 11 months of monthly administration, the study did not find a significant decrease in UPDRS III scores in the "off" condition for patients receiving bee venom injections. Additionally, there were no significant differences in UPDRS III scores over the study course or in nuclear imaging between the treatment and placebo groups. Four patients were excluded from the trial due to positive skin tests, but no systemic allergic reactions were recorded. Notably, specific IgE against bee venom, which initially increased, decreased in all patients who completed the trial. The study suggests that bee venom administration was safe in non-allergic subjects.

[2] USDA Photo

While this study did not reveal clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11-month period compared to placebo, it lays the groundwork for further exploration. The safety of bee venom administration in non-allergic subjects is promising, and the study suggests that higher administration frequency and possibly higher individual doses of bee venom may be necessary to unveil its potency in treating Parkinson's disease. The therapy treatment time might also need to be lengthened to longer than just an 11 month process, in order for the bee venom to have a more impactful and lasting effect. Parkinson’s Disease treatment options have always been experimental in the hopes to find a more holistic way to treat this disease. This research contributes valuable insights to the growing body of knowledge surrounding unconventional therapies for neurodegenerative diseases. As we continue to explore the intricate relationship between bee venom and Parkinson's disease, future studies may refine protocols and administration frequencies to unlock the full therapeutic potential of this intriguing avenue. The journey towards innovative Parkinson's disease treatments is a complex one, but each study brings us one step closer to improving the lives of those affected by this challenging condition.


Further Reading:

DeMarco, S., & Profile., F. (n.d.). Musical Medicine for Parkinson’s Disease. Drug Discovery News. https://www.drugdiscoverynews.com/musical-medicine-for-parkinson-s-disease-15805

Hartmann A, Müllner J, Meier N, Hesekamp H, van Meerbeeck P, Habert M-O, et al. (2016) Bee Venom for the Treatment of Parkinson Disease – A Randomized Controlled Clinical Trial. PLoS ONE 11 (7): e0158235. doi:10.1371/journal.pone.0158235

Hoehn and Yahr Scale. Physiopedia. (n.d.). https://www.physio-pedia.com/Hoehn_and_Yahr_Scale.

Immunoglobulin E (IGE) defined. American Academy of Allergy Asthma & Immunology. (n.d.). https://www.aaaai.org/tools-for-the-public/allergy,-asthma-immunology-glossary/immunoglobulin-e-(ige)-defined.

MDS Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Parkinson’s UK. (2022, November 24). https://www.parkinsons.org.uk/professionals/resources/mds-unified-parkinsons-disease-rating-scale-mds-updrs.

Migrator. (n.d.). Bee Venom therapy: What it is, benefits, safety, Side Effects & Drug Interactions. healthday. https://www.healthday.com/a-to-z-health/alternative-medicine/bee-venom-therapy-647499.html

Professional, C. C. medical. (n.d.). Dopamine: What it is, Function & Symptoms. Cleveland Clinic. https://my.clevelandclinic.org/health/articles/22581-dopamine.

Professional, C. C. medical. (n.d.-b). Nuclear medicine imaging: What it is & how it’s done. Cleveland Clinic. https://my.clevelandclinic.org/health/diagnostics/4902-nuclear-medicine-imaging.

WebMD. (n.d.-b). The placebo effect: What is it?. WebMD. https://www.webmd.com/pain-management/what-is-the-placebo-effect

 

Media Credits:

[1]: Photo by David Hoffman. License: CC BY-NC-SA 3.0

[2]: Public domain image https://commons.wikimedia.org/wiki/File:USDA_entomology_bee_inspection_(12813167043).jpg

Beyond the Buzz: Uncovering the Healing Properties of Bee Venom

By Annie Adams, Paige Fuelling, & Magdalena Pujals

[1] Photo of a bee by Pimthida

Radioactive spiders have grown to fame after the miraculous transformation of Peter Parker in Marvel’s Spiderman. After being bitten, the spider venom provides Peter Parker with superpowers. Although Spiderman is fictional and there are no radioactive spiders that provide superpowers to humans yet, bees provide many super-services to human ailments and diseases. And no, these bees are not radioactive, but their venom can provide a natural, inflammation reducing effect. Bee venom has been examined by scientists in recent years to evaluate its usefulness in treating rheumatoid arthritis.

Rheumatoid arthritis, or RA, is a chronic inflammatory disorder that commonly affects joints as well as other body systems like the skin, eyes, lungs and heart. This form of arthritis causes inflammation that is associated with pain, swelling, and stiffness. Rheumatoid arthritis is one of the most common autoimmune diseases with prevalence increasing globally. Now, around 1% of the population worldwide has rheumatoid arthritis. Without proper management of this disease, serious functional disabilities may develop.

Doaa Mohamed El‑Tedawy and colleagues conducted research on rheumatoid arthritis and the inflammation reducing abilities of bee venom in rats. Bee venom contains various peptides, which are considered the “building blocks” of proteins. These peptides have been found to provide benefits for skin, muscles, and even weight. Already used in traditional Chinese medicine for the treatment of inflammatory diseases and associated pain, bee venom is a natural alternative to drugs like methotrexate. Like bee venom, this option has reduced inflammation and pain which has led it to be a common treatment for rheumatoid arthritis.

The researchers were trying to find if bee venom injections were as successful as standard drugs for treating arthritis in rats. Using an animal disease model, the researchers induced arthritis in 20 adult male Wistar rats by injecting 0.3ml CFA into each right knee joint, and then controlled for it by injecting 0.3ml saline into each left knee joint, marking each injection point. Rats were arthritic if they experienced redness/swelling in a joint. The rats were randomly assigned to 4 groups: healthy, arthritic and treated with saline as a control group, arthritic treated with methotrexate to compare a standard drug against bee venom, and arthritic treated with bee venom (BV). Rats were given a standard dose of methotrexate and 60 mg/kg of BV, which was selected through a prior screening process. Injections started 1 day after induction of arthritis and lasted for 21 days. The researchers harvested the rats' joints to measure how much their joints swelled before, during, and after the experiment.

[2] Illustration of a lab rat

The researchers found that BV works as well as standard drugs in helping to reduce the effects of RA in the rats. Overall, bee venom reduced arthritis, reduced inflammation, and reduced pain for the rats in the experiment.

Although this study, and others, have come to these conclusions, these experiments have only been performed on rats. Before any conclusions can be made for the broader implications of the findings for humans, more research must be conducted, specifically testing BV injections on humans with arthritis. But, something that this experiment doesn’t account for is that the rats were induced with arthritis, whereas rheumatoid arthritis is an autoimmune disorder that humans naturally develop. Therefore, the results of the induced disease experiment may not be transferable to a naturally-occurring disease in humans.

Although Peter Parker’s radioactive spiders and their intriguing transferable properties merely provide entertainment for humanity, there is hope that bees and their venom can help those who suffer from rheumatoid arthritis in the real world. However, the research conducted on their rats is only a stepping stone in discovering how BV can help humans suffering from RA.



Further Reading:

• Benton AW, Morse RA, Stewart JD. Venom Collection from Honey Bees. Science. 1963 Oct 11;142(3589):228-30. doi: 10.1126/science.142.3589.228. PMID: 17834840.

• Darwish, S. F., El-Bakly, W. M., Arafa, H. M., & El-Demerdash, E. (2013). Targeting TNF-α and NF-κB activation by bee venom: role in suppressing adjuvant induced arthritis and methotrexate hepatotoxicity in rats. PloS one, 8(11), e79284. https://doi.org/10.1371/journal.pone.0079284.

• El‑Tedawy, D.M., Abd‑Alhaseeb, M.M., Helmy, M.W., & Ghoneim, A.I. (2020). Systemic bee venom exerts anti‑arthritic and anti‑inflammatory properties in a rat model of arthritis. Biomedical Reports, 13, 20. https://doi.org/10.3892/br.2020.1327.

• Kocyigit, A., Guler, E. M., & Kaleli, S. (2019). Anti-inflammatory and antioxidative properties of honey bee venom on Freund's Complete Adjuvant-induced arthritis model in rats. Toxicon : official journal of the International Society on Toxinology, 161, 4–11. https://doi.org/10.1016/j.toxicon.2019.02.016.

Media credits:

[1] Bee photo by Pimthida. License: CC BY-NC-ND 2.0 DEED
[2] Combination of Google noto 15.1 emojis. License: https://github.com/googlefonts/noto-emoji/blob/main/LICENSE