Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 7930

Special Issue Editors

College of Korean Medicine, Dongshin University, 67 Dongshindae-gil, Naju 58245, Republic of Korea
Interests: venom; drug discovery; pharmacology; herbal medicine; immune response
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Guest Editor
Department of Policy Development, National Institute of Korean Medicine Development, Seoul, Republic of Korea
Interests: endometriosis; infertility; pain management; herbal medicines; pharmacopuncture (herbal acupuncture)
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Special Issue Information

Dear Colleagues,

Bee venom therapy is used to treat musculoskeletal diseases (e.g., low back pain, knee osteoarthritis), Parkinson’s disease, adhesive capsulitis, and polycystic ovary syndrome; snake venom-based drugs are used to treat hypertension, heart attack, acute coronary syndrome, stroke, pulmonary embolism, and other diseases; scorpion venom has strong anti-inflammatory, antibacterial, and anticancer effects. New species of venomous animals are being discovered, requiring the establishing of the venom profiles and molecular mechanisms of venom action. Thus, in order to apply animal toxins to disease treatment, the establishment of clinical evidence and the verification of safety are required. However, recent basic/clinical knowledge has been lacking in the diverse clinical use of animal venoms, despite many off-label uses for them.

Thus, this Toxins Special Issue is devoted to understanding basic knowledge and clinical evidence for therapeutic effects and the safety of animal venoms for treating various diseases.

Dr. Gihyun Lee
Dr. Soo-Hyun Sung
Guest Editors

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Keywords

  • animal venom
  • snail venom
  • spider venom
  • scorpion venom
  • snake venom
  • bee venom
  • clinical study
  • systematic review
  • clinical practice guidelines (CPG)
  • therapeutic effects and its mechanism
  • safety and adverse events

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Published Papers (7 papers)

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Research

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13 pages, 2838 KiB  
Article
Anti-Tumor Effects of Vespa bicolor Venom on Liver Cancer: In Vitro and In Vivo Studies
by Yong-Hua Wu, Feng Xiong, Zheng-Wen Ou, Jing-An Wang, Jing Cui, Lin Jiang and Wen-Jian Lan
Toxins 2025, 17(1), 4; https://doi.org/10.3390/toxins17010004 - 25 Dec 2024
Viewed by 956
Abstract
Despite the popular belief in the anti-tumor properties of Vespa bicolor venom (VBV), there is limited scientific evidence to support this claim. This study is the first to examine the anti-tumor effects of VBV on liver cancer, both alone and in combination with [...] Read more.
Despite the popular belief in the anti-tumor properties of Vespa bicolor venom (VBV), there is limited scientific evidence to support this claim. This study is the first to examine the anti-tumor effects of VBV on liver cancer, both alone and in combination with cisplatin (DDP), through in vitro and in vivo experiments. In vitro experiments evaluated VBV and its combination with DDP on HepG2 cell proliferation, invasion, migration, and apoptosis. Animal studies examined the tumor-suppressive effects, safety (hepatotoxicity and nephrotoxicity), and immune impact of these treatments in tumor-bearing mice. VBV monotherapy significantly inhibited the growth of HepG2 cells by suppressing their proliferation and invasion and induced apoptosis in vitro. Notably, low VBV concentrations significantly promoted the proliferation of normal liver cells (L-02), suggesting a hepatoprotective effect. In vivo, VBV monotherapy enhanced immune function and exhibited tumor suppression comparable to DDP monotherapy but did not induce significant liver or kidney damage. In addition, VBV combined with DDP synergistically enhanced the anti-tumor effects of DDP, compensating for its limited apoptosis-inducing activity and insufficient enhancement of immune function. Initial studies have shown the strong potential of VBV as an anti-liver-tumor drug, highlighting its unique clinical value. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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13 pages, 1264 KiB  
Article
Revealing the Bioactivities of Physalia physalis Venom Using Drosophila as a Model
by Zuzanna Tomkielska, Jorge Frias, Nelson Simões, Bernardo P. de Bastos, Javier Fidalgo, Ana Casas, Hugo Almeida and Duarte Toubarro
Toxins 2024, 16(11), 491; https://doi.org/10.3390/toxins16110491 - 15 Nov 2024
Viewed by 1622
Abstract
Physalia physalis, commonly known as the Portuguese Man o’ War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of P. physalis venom by assessing its behavioral and toxicological effects on Drosophila [...] Read more.
Physalia physalis, commonly known as the Portuguese Man o’ War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of P. physalis venom by assessing its behavioral and toxicological effects on Drosophila melanogaster. The venom administered orally revealed dose- and time-dependent mortality, with an LD50 of 67.4 μg per fly. At sublethal doses, the treated flies displayed uncoordinated movement and fell when attempting to climb. Real-time analysis of flies exposed to the venom revealed hyperexcitability followed by paralysis, with phenotypes similar to those observed in vertebrate models. The venom was shown to be non-thermolabile, as no significant differences in behavior and locomotion were observed between flies exposed to untreated or thermally treated venom. The circadian rhythm alterations, the enhanced light attraction, and the reduction in heat avoidance suggest altered neuronal function. This abnormal behavior indicates that the venom contains bioactive molecules, opening avenues for discovering new compounds with potential for pharmacological applications. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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Review

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19 pages, 535 KiB  
Review
Bee Venom Acupuncture in Traditional Korean Medicine: A Review of Clinical Practice Guidelines
by Minjung Park and Seungwon Shin
Toxins 2025, 17(4), 158; https://doi.org/10.3390/toxins17040158 - 22 Mar 2025
Viewed by 413
Abstract
Bee venom acupuncture (BVA) is used in traditional Korean medicine (TKM) for various diseases, but its evaluation within clinical practice guidelines (CPGs) has not been comprehensively reviewed. This study aimed to review TKM-CPGs to characterize the range of conditions for which BVA is [...] Read more.
Bee venom acupuncture (BVA) is used in traditional Korean medicine (TKM) for various diseases, but its evaluation within clinical practice guidelines (CPGs) has not been comprehensively reviewed. This study aimed to review TKM-CPGs to characterize the range of conditions for which BVA is recommended, summarize the level of evidence and recommendation grades, and assess the factors influencing the grades. Eighteen TKM-CPGs, including 30 BVA-related recommendations, were identified. Data on targeted diseases/symptoms, treatment protocols, evidence levels, and recommendation grades were extracted. The CPGs recommended BVA for musculoskeletal and neurological disorders in standalone or combined therapy. Most of the evidence for BVA recommendations was evaluated with low to moderate levels based on randomized controlled trials. The grades of recommendations were mostly B or C, indicating that BVA is advisable or potentially beneficial. Although the CPGs offer some guidance on treatment protocols for BVA, there remains a lack of detailed specifications, and we need to conduct additional research to provide evidence. Also, the heterogeneity of recommendations across different CPGs presents a challenge in establishing consistent clinical guidelines. Future research should focus on generating high-quality evidence and standardizing treatment regimens to support more robust recommendations for BVA in TKM clinical practice. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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13 pages, 258 KiB  
Review
Effectiveness of Scolopendrid Pharmacopuncture for Neuropathic Dysfunction: Clinical Evidence and Potential Mechanism
by Jung-Hyun Kim, Tae-Yoon Kim, Bonhyuk Goo and Sang-Soo Nam
Toxins 2025, 17(2), 83; https://doi.org/10.3390/toxins17020083 - 12 Feb 2025
Viewed by 927
Abstract
Animal venoms, particularly Scolopendrid venom, have gained significant attention as therapeutic agents in complementary and alternative medicine, especially for applications in pain management and neuroprotection. In traditional Korean medicine, Scolopendrid venom is administered through pharmacopuncture, a method that combines injection therapy with principals [...] Read more.
Animal venoms, particularly Scolopendrid venom, have gained significant attention as therapeutic agents in complementary and alternative medicine, especially for applications in pain management and neuroprotection. In traditional Korean medicine, Scolopendrid venom is administered through pharmacopuncture, a method that combines injection therapy with principals of acupuncture. The present review focuses on the multifaceted effects of Scolopendrid pharmacopuncture, derived from Scolopendra polymorpha, on the peripheral nervous system, and its potential role in addressing the neuropathic dysfunction that often arises from peripheral nerve injuries. Scolopendrid venom exhibits various pharmacological properties, including analgesic, anti-inflammatory, and neuroprotective effects. Experimental studies have shown that Scolopendrid pharmacopuncture significantly reduces neuropathic pain in animal models by modulating ion channels and inflammatory pathways. Clinical investigations have further revealed its efficacy in alleviating pain associated with conditions such as Bell’s palsy and carpal tunnel syndrome. Despite its promising therapeutic potential, the lack of comprehensive clinical research on the toxicity and safety profiles of SPP remains a critical limitation. Future studies should focus on evaluating the safety of Scolopendrid venom as a standalone treatment and incorporate broader data sources to enhance our understanding of its implications in clinical practice. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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13 pages, 539 KiB  
Review
Bee Venom Acupuncture for Shoulder Pain: A Literature Review of Clinical Studies
by Hyein Jeong, Soobin Jang, Jang-Kyung Park, Kyeong Han Kim, Jong Hyun Park, Gihyun Lee and Soo-Hyun Sung
Toxins 2024, 16(11), 501; https://doi.org/10.3390/toxins16110501 - 20 Nov 2024
Cited by 2 | Viewed by 1577
Abstract
Managing shoulder pain typically involves the use of acetaminophen or oral nonsteroidal anti-inflammatory drugs, but prolonged use of these medications can lead to dependence and various side effects. To overcome the dose dependency and side effects of these conventional drugs, animal venoms have [...] Read more.
Managing shoulder pain typically involves the use of acetaminophen or oral nonsteroidal anti-inflammatory drugs, but prolonged use of these medications can lead to dependence and various side effects. To overcome the dose dependency and side effects of these conventional drugs, animal venoms have begun to be utilized. Among them, bee venom stands out for its powerful anti-inflammatory properties, which help relieve pain and treat chronic inflammatory conditions. This review evaluates the efficacy and safety of bee venom acupuncture (BVA) for shoulder pain. In March 2024, we searched 11 databases: 5 international and 6 Korean databases. We identified 23 clinical studies on BVA for shoulder pain. The causes of shoulder pain were post-stroke pain (43.5%), rotator cuff syndrome (17.4%), and brachial plexus palsy (13.0%). The BVA concentration and dosage per session were 0.005–1.0 mg/mL and 0.01–2.0 mL, respectively. All included clinical studies reported positive effects on pain outcomes. This review suggests that BVA, which involves injecting bee venom into acupuncture points, may serve as a viable alternative for pain management. However, the level of evidence in the included studies was low and adverse effects were reported infrequently, indicating that further research is needed. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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12 pages, 1022 KiB  
Review
Clinical Effectiveness of Bee Venom Acupuncture for Bone Fractures and Potential Mechanisms: A Narrative Overview
by Jung-Hyun Kim and Byung-Kwan Seo
Toxins 2024, 16(11), 465; https://doi.org/10.3390/toxins16110465 - 31 Oct 2024
Cited by 1 | Viewed by 1625
Abstract
Bee venom acupuncture, a type of herbal acupuncture, combines the pharmacological actions of bioactive compounds from bee venom with the mechanical stimulation of meridian points. Bee venom acupuncture is gaining popularity, particularly in the Republic of Korea, primarily for pain relief of various [...] Read more.
Bee venom acupuncture, a type of herbal acupuncture, combines the pharmacological actions of bioactive compounds from bee venom with the mechanical stimulation of meridian points. Bee venom acupuncture is gaining popularity, particularly in the Republic of Korea, primarily for pain relief of various conditions. This study aimed to summarize and evaluate the available evidence on the use of bee venom acupuncture for recovery after bone fractures. Electronic literature searches for experimental studies and clinical trials were conducted using the PubMed, China Academic Journals (CAJ), and OASIS databases. The search revealed 31 studies, of which six met our criteria. These studies demonstrated that bee venom acupuncture can be effective in treating bone fractures, suggesting a promising area for future research. However, evidence supporting its efficacy in this context is limited. Rigorous trials with large sample sizes and robust designs are needed to clarify the role of bee venom acupuncture for these indications. In addition, future studies should explore the optimal dosage and concentration of bee venom acupuncture. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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Other

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15 pages, 1265 KiB  
Systematic Review
Effectiveness of Bee Venom Injection for Parkinson’s Disease: A Systematic Review
by Hyein Jeong, Kyeong Han Kim and Seong-gyu Ko
Toxins 2025, 17(4), 204; https://doi.org/10.3390/toxins17040204 - 20 Apr 2025
Viewed by 258
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, affecting over 8.5 million people as of 2019. While standard pharmacological treatments help alleviate symptoms, their long-term use can lead to side effects such as dyskinesia. Bee venom acupuncture (BVA) involves the [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, affecting over 8.5 million people as of 2019. While standard pharmacological treatments help alleviate symptoms, their long-term use can lead to side effects such as dyskinesia. Bee venom acupuncture (BVA) involves the use of a natural toxin derived from bees that can be used for pain relief and treating neurological disorders. This study aimed to review the efficacy and safety of BVA for the treatment of PD. This review protocol was prospectively registered with PROSPERO (CRD420251000577). We searched eight databases in February 2025 and selected 12 studies involving 215 PD patients treated with BVA. Idiopathic Parkinson’s disease (IPD) is the most common diagnosis. The concentration and dosage per session ranged from 0.03 to 0.1 mg/mL and from 0.1 to 1.0 mL, respectively. Twenty-four different outcome measures were used, with the Unified PD Rating Scale employed in 91.7% of the studies. All studies reported improvements in outcomes. Mild adverse effects such as swelling and itching were noted in four studies (33.3%); however, no severe reactions such as anaphylactic shock occurred. These findings suggest that BVA has the potential for broader clinical applications in the treatment of PD. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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