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While the survival rate has increased due to treatments for breast cancer, the quality of life has decreased because of the side effects of chemotherapy. Various toxins are being developed as alternative breast cancer treatments, and bee venom is drawing attention as one of them. We analyzed the effect of bee venom and its components on breast cancer cells and reviewed the mechanism underlying the anticancer effects of bee venom. Data up to March 2022 were searched from PubMed, EMBASE, OASIS, KISS, and Science Direct online databases, and studies that met the inclusion criteria were reviewed. Among 612 studies, 11 were selected for this research. Diverse drugs were administered, including crude bee venom, melittin, phospholipase A2, and their complexes. All drugs reduced the number of breast cancer cells in proportion to the dose and time. The mechanisms of anticancer effects included cytotoxicity, apoptosis, cell targeting, gene expression regulation, and cell lysis. Summarily, bee venom and its components exert anticancer effects on human breast cancer cells. Depending on the mechanisms of anticancer effects, side effects are expected to be reduced by using various vehicles. Bee venom and its components have the potential to prevent and treat breast cancer in the future.

Breast cancer remains a leading cause of cancer-related mortality worldwide, necessitating innovative therapeutic approaches. This scoping review summarizes experimental evidence on the anticancer activity of snake venom and its bioactive components against breast cancer, drawing from a variety of in vitro and in vivo studies. Aimed at critically evaluating the therapeutic potential and underlying mechanisms, this review consolidates findings on venoms from multiple snake species, including both crude preparations and purified proteins or peptides, revealing a diversity of mechanisms of action. Reported effects include induction of apoptosis, generation of reactive oxygen species, disruption of cell membrane integrity, inhibition of cell proliferation and metastasis, and modulation of oncogenic signaling pathways. In vivo findings further indicate tumor growth inhibition and, in some cases, enhanced efficacy when venom-based agents are combined with nanoparticle delivery systems or conventional anticancer drugs. However, a significant proportion of evidence is limited to in vitro studies, with substantial heterogeneity in venom sources, extraction methods, dosages, and cancer models, which constrains generalizability. There is also a lack of systematic data on long-term toxicity, immunogenicity, off-target effects, pharmacokinetics, and formulation challenges. Taken together, these findings highlight snake venom-derived compounds as promising multi-targeted anticancer agents but underscore the urgent need for standardized formulations, rigorous preclinical safety assessments, and translational research to bridge the gap to clinical application. Future investigations should aim to isolate novel venom-derived compounds, refine delivery strategies, and undertake rigorous preclinical safety and pharmacokinetic studies—ultimately moving toward early-phase clinical evaluation to bridge the translational gap and assess the therapeutic potential of these agents.

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.

Infertility is an emerging health issue worldwide, and female infertility is intimately associated with embryo implantation failure. Embryo implantation is an essential process during the initiation of prenatal development. Recent studies have strongly suggested that autophagy in the endometrium is the most important factor for successful embryo implantation. In addition, several studies have reported the effects of various natural products on infertility improvement via the regulation of embryo implantation, embryo quality, and endometrial receptivity. However, it is unclear whether natural products can improve embryo implantation ability by regulating endometrial autophagy. Therefore, we performed a literature review of studies on endometrial autophagy, embryo implantation, natural products, and female infertility. Based on the information from these studies, this review suggests a new treatment strategy for female infertility by proposing natural products that have been proven to be safe and effective as endometrial autophagy regulators; additionally, we provide a comprehensive understanding of the relationship between the regulation of endometrial autophagy by natural products and female infertility, with an emphasis on embryo implantation.

Endometriosis is a chronic inflammatory disorder caused by abnormal adhesion of endometrial tissue to the outside of the uterus. The combination of surgery, non-steroidal anti-inflammatory drugs, and hormone treatment is well established therapy for endometriosis, however, case reports have showed that high rates of relapse and unpleasant side effect. For these reasons, recently, the studies have been focused on the Warburg-like metabolic shift of endometriosis. Prunella vulgaris is one of traditionally used herbal medicine for inflammatory disease and the anti-estrogenic effects of P. vulgaris is well-established. Therefore, in this work, we evaluated water-extracted P. vulgaris (PV) as a potential treatment for endometriosis. To this, we artificially induced endometriosis in ovarectomized mice by intra-peritoneal inoculation of uterus extracts. PV was orally administered, and PV significantly alleviated endometriosis, particularly the growth of ectopic endometrial lesions in artificially endometriosis-induced mice. For the mechanism study of anti-endometriosis by PV, we designed an in vitro study using human normal endometrial stromal cells (T-HESCs) and human endometrial cell (12Z) obtained from patients with endometriosis. PV strongly induced the apoptosis of 12Z cells rather than T-HESCs by control the activity or expression of aerobic glycolysis enzymes, such as lactate dehydrogenase A (LDHA), pyruvate dehydrogenase A, and pyruvate dehydrogenase kinase 1/3. In addition, lactate production was enhanced, and oxygen consumption rate was suppressed in 12Z cells upon PV treatment. These changes in aerobic glycolysis eventually caused mitochondrial damage following decreased mitochondrial membrane potential and excessive mitochondrial ROS production. Especially, ulsolic acid (UA), one of the compounds in PV considerably led 12Z cell apoptosis with inhibition of LDHA activity. Therefore, UA could be a major active substance of PV in terms of endometriosis inhibitors. In conclusion, this study provides the evidence that the beneficial efficacy of PV for the prevention/treatment of endometriosis.

An updated systematic review of randomized controlled trials (RCTs) was conducted to evaluate the clinical evidence for the use of BVA for musculoskeletal pain. We searched 13 electronic databases up to December 2024 with no language restrictions. Since 2008, nine RCTs have been additionally identified, so a total of 20 trials were included in our updated review. In a meta-analysis of 2 RCTs, pain was significantly reduced with BVA compared to sham injection of normal saline (10-cm visual analog scale [VAS]; mean difference [MD]: -16.93; 95% confidence interval [CI] = -26.35 to -7.51, P  = 0.0004, n  = 85; heterogeneity: I 2  = 0%). The meta-analysis of 5 RCTs comparing BVA plus acupuncture to saline injection plus acupuncture showed significant improvements in the 10-cm VAS (MD: -1.24; 95% CI = -1.63 to -0.85, P  < 0.00001, n  = 152; heterogeneity: I 2  = 16%). No severe side effects such as anaphylaxis were observed in any of the eight trials. BVA appeared to improve musculoskeletal pain conditions compared to sham injections. However, the meta-analysis included only a limited number of RCTs with small sample sizes, and there was considerable clinical heterogeneity in terms of pain types, dosage, and concentration of BVA, which restricts the ability to draw definitive conclusions.

This study aimed to identify all of the characteristics of bee venom acupuncture (BVA) for the treatment of lower back pain (LBP) that are described in the Korean literature, and to provide English-speaking researchers with bibliometrics. Six Korean electronic databases and sixteen Korean journals on BVA treatment for back pain were searched up to February 2022. This report included and analyzed 64 clinical studies on BVA interventions for back pain and 1297 patients with LBP. The most common disease in patients with back pain was lumbar herniated intervertebral discs (HIVD) of the lumbar spine (L-spine). All studies used bee venom (BV) diluted with distilled water. The concentration of BVA for HIVD of L-spine patients with LBP ranged from 0.01 to 5.0 mg/mL; the dosage per treatment was 0.02–2.0 mL, and for a total session was 0.3–40.0 mL. The most used outcome measure was the visual analogue scale for back pain (n = 45, 70.3%), and most of the papers reported that each outcome measure had a positive effect. Korean clinical studies were typically omitted from the review research, resulting in potential language bias. This study provides clinical cases in Korea for future development and standardization of BVA treatment for back pain.

Overactive bladder (OAB) is a common condition in older women, characterized by urinary urgency, frequency, and nocturia. This study compared the efficacy and safety of thread-embedding acupuncture (TEA) and sham TEA in postmenopausal women with OAB. In this multicenter, randomized, controlled trial, 68 postmenopausal women with OAB were allocated in a 1:1 ratio to receive TEA or sham TEA (manual acupuncture without thread embedding) once weekly for 8 weeks, followed by an 8-week follow up. The primary outcome was the mean daily voiding frequency over 3 days. Secondary outcomes included other bladder diary parameters, the Overactive Bladder Symptom Score (OABSS), and the King's Health Questionnaire score. At week 8, both groups showed reductions in 24-hour micturition frequency; however, after adjustment for baseline values using ANCOVA, no significant between-group difference was observed in the primary outcome. Repeated measures analysis demonstrated no significant group-by-time interactions for secondary outcomes, although significant improvements over time were observed in both groups. At follow-up, nighttime voiding remained significantly reduced from baseline in the TEA group, whereas this reduction was not statistically significant in the sham group; however, the between-group difference did not reach statistical significance. No serious adverse events were reported. TEA and manual acupuncture were effective and safe in reducing OAB symptoms in postmenopausal women, with no significant differences between interventions. Larger, long-term studies are needed to clarify specific benefits of TEA.

Background/Objectives: Breast cancer remains the most prevalent malignancy among women worldwide. Innovative therapies are essential to address its diverse subtypes and treatment resistance. Scorpion venom and its bioactive proteins have gained attention as potential anticancer agents owing to their multitargeted cellular effects. This review systematically evaluates their anticancer properties and mechanisms in breast cancer, highlighting therapeutic potential. Methods: A systematic search was conducted in five databases (PubMed, Science Direct, EMBASE, OVID, and KISS) up to September 2024. Only in vitro studies using breast cancer cell lines and investigating scorpion venom or its bioactive proteins were included. Extracted data covered study characteristics, intervention types, control groups, dose range, duration, and key outcomes. Results: In total, 19 studies met the eligibility criteria. Crude scorpion venom showed broad cytotoxicity against hormone receptor-positive, triple-negative, and HER2-positive breast cancer subtypes. The primary mechanisms included apoptosis induction, DNA fragmentation, oxidative stress modulation, and cell cycle regulation. Bioactive proteins, such as chlorotoxin (CTX) and Neopladine 1/2, exhibited selective anticancer effects by targeting signaling pathways, inhibiting migration and invasion, and promoting apoptosis. Conclusion: These findings support scorpion venom’s potential as a multitargeted anticancer agent. The complementary actions of crude venom and its proteins highlight their promise for combination therapies. Further research is needed to clarify their synergistic interactions and optimize preclinical and clinical applications.

Yeosinsan, an herbal formula composed of roots of Paeonia lactiflora and tubers of Cyperus rotundus, was reported as a possible anti-inflammatory and pro-fertility drug. However, the safety of Yeosinsan has not yet been previously investigated. The possible acute and chronic oral toxicity of Yeosinsan was estimated using female and male Sprague Dawley rats. During the administration period, rats were monitored for mortality, body weight changes, food intake, clinical signs, and gross findings. Hematological analysis, serum biochemistry analysis, urinalysis, organ weight measurement, and histopathological examination were also conducted after sacrifice. Acute and chronic oral administration of Yeosinsan did not result in any signs of toxicity in the animals during the observation period. However, in the histopathological examination, several significant changes were observed in the stomach and spleen. In the high-dose group, extramedullary hematopoiesis and increased pigmentation in the spleen and squamous cell hyperplasia in the forestomach were observed. In conclusion, the no observed adverse effect level (NOAEL) of the test material, Yeosinsan, was estimated at 1000 mg∙kg−1∙d−1 for both male and female rats. Therefore, our data suggest that Yeosinsan might be safe to use for treating female infertility.