Component Of Bee Venom Research Articles

Structures of calmodulin–melittin complexes show multiple binding modes lacking classical anchoring interactions

Calmodulin (CaM) is a Ca2+ sensor protein found in all eukaryotic cells that regulates a large number of target proteins in a Ca2+ concentration-dependent manner. As a transient type hub protein, it recognizes linear motifs of its targets, though for the Ca2+-dependent binding no consensus sequence was identified. Its complex with melittin, a major component of bee venom, is often used as a model system of protein - protein complexes. Yet, the structural aspects of the binding are not well understood, as only diverse, low-resolution data are available concerning the association. We present the crystal structure of melittin in complex with Ca2+-saturated calmodulins from two, evolutionarily distant species, Homo sapiens and Plasmodium falciparum representing three binding modes of the peptide. Results - augmented by molecular dynamics simulations - indicate that multiple binding modes can exist for CaM-melittin complexes, as an intrinsic characteristic of the binding. While the helical structure of melittin remains, swapping of its salt bridges and partial unfolding of its C-terminal segment can occur. In contrast to the classical way of target recognition by CaM, we found that different sets of residues can anchor at the hydrophobic pockets of CaM, which were considered as main recognition sites. Finally, the nanomolar binding affinity of the CaM-melittin complex is created by an ensemble of arrangements of similar stability - tight binding is achieved not by optimized specific interactions but by simultaneously satisfying less optimal interaction patterns in co-existing different conformers.

Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance.

Multidrug resistance (MDR) is one of the major barriers in chemotherapy. It is often related to the overexpression of efflux receptors such as P-glycoprotein (P-gp). Overexpressed efflux receptors inhibit chemotherapeutic efficacy by pumping out intracellularly delivered anticancer drugs. In P-gp-mediated MDR-related pathways, PI3K/Akt and NF-kB pathways are commonly activated signaling pathways, but these pathways are downregulated by melittin, a main component of bee venom. In this study, a polymersome based on a poly (lactic acid) (PLA)-hyaluronic acid (HA) (20k-10k) di-block copolymer and encapsulating melittin and doxorubicin was developed to overcome anticancer resistance and enhance chemotherapeutic efficacy. Through the simultaneous delivery of doxorubicin and melittin, PI3K/Akt and NF-κB pathways could be effectively inhibited, thereby downregulating P-gp and successfully enhancing chemotherapeutic efficacy. In conclusion, a polymersome carrying an anticancer drug and melittin could overcome MDR by regulating P-gp overexpression pathways.

Arı zehirinin yağ dokusu kaynaklı mezenkimal kök hücre üzerindeki yara iyileştirici etkileri

The objective of this study is to determine the effects of bee venom on the proliferation capacity of mesenchymal stem cells and wound healing. For this purpose, mesenchymal stem cells were isolated from canine adipose tissue and bee venom samples were collected from Apis mellifera anatoliaca in Muğla province of Türkiye. Cell viability test was performed on mesenchymal stem cells exposed to various concentrations (40 ppm, 20 ppm, 10 ppm, 5 ppm, 2.5 ppm, 1.25 ppm, 0.625 ppm and 0.312 ppm) of bee venom. And wound healing test was performed on cells treated with the doses (5 ppm, 2.5 ppm, 1.25 ppm, 0.625 ppm) and imaged every two hours for 16 hours. According to the results of our study's cell proliferation assay and wound healing test, bee venom had no proliferative effect on mesenchymal stem cells within the defined dose range. The study's outcomes may be enhanced by investigating the effect of bee venom on mesenchymal stem cells in combination with other substances or by improving the bee venom's purification process. Even while we have a better understanding of the mechanisms of action of bee venom components, there are still a lot of unanswered questions on the subject. It is believed that figuring out how bee venom affects wound healing may be useful for advancing wound care in both veterinary and human medicine.

Key Genes Are Associated with the Prognosis of Glioma, and Melittin Can Regulate the Expression of These Genes in Glioma U87 Cells.

Glioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for glioma. Melittin (MT) is the main component of bee venom, which was found to have therapeutic effects on a variety of tumors. In this study, we explored the relationship between key genes regulated by MT and the prognosis of glioma. In cultured glioma U87 and U251 cells, MT inhibited cell proliferation and induces cell apoptosis in a time- and concentration-dependent manner. RNA-seq revealed that MT upregulated 11 genes and downregulated 37 genes. These genes are mainly enriched in cell membrane signaling pathways, such as surface membrane, membrane-enclosed organelles, integral component of membrane, PPAR signaling pathway, and voltage-gated potassium channel. PPI network analysis and literature analysis of 48 genes were performed, and 8 key genes were identified, and these key genes were closely associated with clinical prognosis. Overexpression of PCDH18, PPL, DEPP1, VASN, KCNE4, MYBPH, and C5AR2 genes or low expression of MARCH4 gene in glioma patients was associated with poor survival. qPCR confirmed that MT can regulate the expression of these genes in glioma U87 cells. This study indicated that MT significantly inhibited the growth and regulated the expression of PCDH18, C5AR2, VASN, DEPP1, MYBPH, KCNE4, PPL, and MARCH4 genes in glioma U87 cells in vitro. These genes are closely related to the prognosis of patients with glioma and can be used as independent prognostic factors in patients with glioma. MT is a potential drug for the treatment of glioma.

Bee Venom Triggers Autophagy-Induced Apoptosis in Human Lung Cancer Cells via the mTOR Signaling Pathway.

In oriental medicine, bee venom has long been used as a therapeutic agent against inflammatory diseases. Several studies have reported that isolated and purified bee venom components are effective in treating dementia, arthritis, inflammation, bacterial infections, and cancer. In previous studies, we reported that bee venom inhibits cell growth and induces apoptotic cell death in lung cancer cells. In the present study, we assessed whether bee venom affects autophagy and thereby induces apoptosis. Bee venom treatment increased the levels of autophagy-related proteins (Atg5, Beclin-1, and LC3-II) and the accumulation of LC3 puncta. We found that bee venom could induce autophagy by inhibiting the mTOR signaling pathway. In addition, we found that hydroxychloroquine (HCQ)- or si-ATG5-induced autophagy inhibition further demoted bee venom-induced apoptosis. Bee venom-induced autophagy promotes apoptosis in lung cancer cells and may become a new approach to cancer treatment.

Melittin regulates iron homeostasis and mediates macrophage polarization in rats with lumbar spinal stenosis

Lumbar spinal stenosis (LSS) is defined as spinal canal narrowing, resulting in the compression of the nerves traversing the lower back into the leg. Inflammation is the most common cause of LSS. Elevated iron stores are often associated with chronic inflammation resulting in nerve damage-induced pain. Macrophage polarization to either the M1 (inflammatory) or M2 (anti-inflammatory) type is essential for regulating host defenses and promoting tissue repair. However, the precise role of macrophage polarization in iron release or retention in LSS pathophysiology remains elusive. Melittin, a component of bee venom, modulates iron metabolism-related macrophage polarization and is beneficial in LSS. We treated primary peritoneal macrophages with melittin and assessed macrophage polarization by immunofluorescence staining. Melittin (100 and 250 µg/kg) effects on iron deposition-induced macrophage polarization were also evaluated using immunochemistry, real-time PCR, and flow cytometry in an LSS rat model. Locomotor function was assessed using the Basso–Beattie–Bresnahan (BBB) locomotor rating scale, ladder scoring, and von Frey test for up to 3 weeks. Melittin induced M2 polarization of iron-insulted primary macrophages in vitro and increased the proportion of M2 macrophages in the damaged spinal cord in vivo. Moreover, melittin attenuated iron overload-induced M1 polarization by regulating iron metabolism-related genes in rats with LSS. In conclusion, melittin improves locomotor recovery and stimulates axonal growth following LSS. Additionally, it promotes functional recovery in LSS rat models by regulating macrophage iron metabolism, thereby activating M2 macrophages, suggesting its potential application in LSS treatment.

Organic acids and their derivatives: minor components of bee pollen, bee bread, royal jelly and bee venom

Organic acids and their derivatives: minor components of bee pollen, bee bread, royal jelly and bee venom

Development and characterization of the electrospun melittin-loaded chitosan nanofibers for treatment of acne vulgaris in animal model

Acne is an inflammatory disease of the sebaceous glands. Melittin (Mel) is one of the principal toxic components of bee venom that can cause antibacterial and anti-inflammatory effects. Chitosan is a biodegradable polysaccharide has anti-inflammatory, antimicrobial, and regenerative properties. In this study, chitosan (Ch)/Mel 0.001 and 0.003% nanofibers were fabricated for topical treatment of acne vulgaris. Physicochemical properties of Ch/Mel were evaluated using FTIR and FESEM. Furthermore, encapsulation efficiency, tensile strength, water absorption capacity, enzymatic activity, drug release, antimicrobial, and cell cytotoxicity were assayed. Animal models were exerted to study the impact of Ch/Mel nanofibers on the treatment of Propionibacterium acnes. The FESEM results showed that nanofibers were successfully prepared in nano-scale fiber diameter. The FTIR confirmed the presence of Mel in structures. The addition of melittin to the polymer solution reduced electrical conductivity, induced viscosity and tensile strength of the fibers, and decreased the percentage of the swelling. The Mel loading into Ch/Mel 0.003% was reported at 86.74±1%. This Mel releasing process (89.65%) of Ch/Mel 0.003% was slowly completed during 72 h. The Mel retained its hemolytic activity after being loaded into the polymer structure. The drug toxicity study displayed the lack of any significant toxicity from Ch/Mel nanofibers on normal Human Dermal Fibroblasts (HDF). The Ch/Mel 0.003% achieved the highest growth inhibition in P. acnes in vitro and animal studies, this group showed the greatest reduction in inflammation and redness. The Ch/Mel 0.003% structure is proposed as a suitable topical drug delivery system for treating acne vulgaris.

Anticancer Activity of Bee Venom Components against Breast Cancer.

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.

Melittin-derived peptides exhibit variations in cytotoxicity and antioxidant, anti-inflammatory and allergenic activities

ABSTRACT Melittin is a major component of bee venom; it is widely used in traditional medicine because of its therapeutic effects, such as anti-inflammatory effects. However, melittin has limited medical applications owing to its adverse effects, such as high cytotoxicity. In this study, we investigated the physiological activities of various hydrolyzed melittin-derived peptides to eliminate the cytotoxicity of melittin and enhance its efficacy. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay confirmed that melittin-derived peptides showed antioxidant activity comparable to that of melittin. Moreover, unlike melittin, which showed high cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)−5-(3-carboxymethoxyphenyl)−2-(4-sulfophenyl)−2H-tetrazolium inner salt (MTS) assay, the melittin-derived peptides showed negligible cytotoxicity. Among the melittin-derived peptides, the peptide composed of sequence TTGLPALISWIKRKRQQ (P1) showed inhibitory effects on the mRNA expression of inflammatory cytokines and phosphorylation of IκBα, similar to the effects of melittin in RAW 264.7 cells. Degranulation of RBL-2H3 cells was analyzed using a β-hexosaminidase release assay to confirm the allergenic activity of melittin and P1, which showed remarkably reduced allergenicity of P1 compared to that of melittin. These results indicate that P1 maintained the anti-inflammatory effects of melittin while reducing its cytotoxicity and allergic reactions. In conclusion, the melittin-derived peptide P1 efficiently decreased the adverse effects while maintaining the beneficial effects of melittin, making it suitable for therapeutic applications.

CD206+ dendritic cells might be associated with Heat-pattern and induced regulatory T cells after treatment with bee venom

Objectives: Bee venom (BV) is a widely used therapy in Traditional East Asian Medicine (TEAM). We previously reported that BV was clinically effective for treating Parkinson’s disease, that phospholipase A2 (PLA2) was the main component of BV, and that it induced regulatory T cells (Tregs) by binding CD206 on dendritic cells (DCs). Therefore, we aimed to reconfirm our findings in human blood samples and investigate the relationship between CD206+ DCs and clinical syndrome differentiation in TEAM.Methods: We surveyed 100 subjects with questionnaires on cold-heat patternization and obtained their blood samples. The obtained human peripheral blood monocytes (hPBMCs) were washed with phosphate-buffered saline (PBS). After resuspension with ex vivo media, numbers of cells were counted. Tregs were counted after culturing the samples in a 37℃ CO2 incubator for 72 h.Results: We divided the subjects into a relatively high CD206+ group or a relatively low CD206+ group. The heat factor scores of high CD206+ group were significantly higher than that of low CD206+ group (high vs low: 239.2 ± 54.1 vs 208.4 ± 55.1, p=0.023). After culturing with PLA2, Tregs increased in the high CD206+ group but decreased in the low CD206+ group.Conclusion: In this study, we reconfirm that CD206+ DCs induced Treg differentiation by incubating human blood samples with PLA2 and that they showed an association with syndrome differentiation, especially with heat patterns, in TEAM. A heat pattern in TEAM might be one indication for PLA2 therapy because its score was elevated in the high CD206+ group.

Properties of some bee products (pollen, roe milk and bee venom), apitherapy and their effects on Covid-19

The new type of coronavirus infection (COVID-19), caused by coronavirus-2 (SARS-CoV-2), has led to a world pandemic due to severe acute respiratory syndrome. In addition to drug and vaccine studies for COVID-19, studies on various foods maintain to increase immunity and alternative treatment, and in this context, bee products are also being researched. Although many studies are showing that bee products have antimicrobial properties and immune-enhancing effects, there are limited studies on the effectiveness of these products against coronavirus. Some peptides in royal jelly are reported to be potent antibacterial and antifungal agents that may be beneficial for avoiding co-infections in COVID-19 patients. Positive results have been found Pollen, a fine and powder-like substance produced by flowering plants and collected by bees, in many studies investigating the effects of pollen on health such as antimicrobial, antiviral and anti-inflammatory. Bee venom; It is a yellowish-colored, bitter-sweet, pungent-smelling substance that is produced in the venom sac of bees, normally in liquid form, but dries up and crystallizes after contact with air. Melittin, the primary component of bee venom having more than 40 biologically and pharmacologically active compounds including phospholipase A2, histamine, epinephrine, free amino acids, peptide and apamin, has been stated to have antitumor, antimicrobial, anti-nociceptive and anti-inflammatory activities. Phospholipase A2 (PLA2) secreted from bee and snake venom is known to have strong anti-HIV activities. Melittin, phosphorylase A2 and hyaluronidan, which are the most significant components of bee venom, constitute 50% of bee venom. Moreover, researches on the relationship between bee venom and COVID-19 are limited. The target of this review is to bring together the studies on the health effects of royal jelly, bee pollen and bee venom, and to contribute to the existing studies.

Melittin: A Natural Peptide with Expanded Therapeutic Applications

Background: Apis mellifera, European honey bee venom (BV) is a complex combination of chemical compounds comprising proteins, peptides, enzymes, and other small molecules. Melittin (MEL), which is the key component of BV is considered as an alternative for treatment of various infections. MEL is an amphipathic, cell-penetrating, 26-residue, ahelical anti-hepatoma peptide derived from BV. However, owing to its initial conformational strength and poor stability, melittin is constrained in use as a medication. Objective: The study focused on collective data of therapeutic activities of Bee venom component, MEL. Method: Regardless of its broad variety of biological and possible therapeutic uses, there has been increasing concern in the use of MEL. According to literature, MEL revealed range of activities started from Anti- cancer activity, Anti- microbial activity, Anti- viral activity, Anti-inflammatory activity to Anti- diabetic activity. Present review article summarized therapeutic applications of MEL, their mechanism of action along with recent research progress in field of its delivery. Conclusion: It could be concluded that MEL exerts multiple effects on cellular functions of infected cells.

Single-molecule phospholipase A2 becomes processive on melittin-induced membrane deformations

While it is established that the topology of lipid membranes plays an important role in biochemical processes, few direct observations exist regarding how the membranes are actively restructured and its consequences on subsequent reactions. In this work, we investigated how the two major components of bee venom, melittin and phospholipase A2 (PLA2), achieve activation by such membrane remodeling. Their membrane-disrupting functions have been reported to increase when both are present, but the mechanism of this synergism had not been established. Using membrane reconstitution, we found that melittin can form large-scale membrane deformities upon which PLA2 activity is 25-fold higher. Tracking of single-molecule PLA2 revealed that its processive behavior on these deformities underlies the enhanced activity. These results show how melittin and PLA2 work synergistically to enhance the lytic effects of the bee venom. More broadly, they also demonstrate how the membrane topology may be actively altered to modulate cellular membrane-bound reactions.

Melittin Prevents Metastasis of Epidermal Growth Factor-Induced MDA-MB-231 Cells through The Inhibition of The SDF-1α/CXCR4 Signaling Pathway.

Objective Melittin is one of the natural components of bee venom (Apis mellifera), and its anticancer and antimetastatic properties have been well established, but the underlying mechanism remains elusive. The MDA-MB-231 is a triple- negative cell line that is highly aggressive and invasive. Besides, many critical proteins are involved in tumor invasion and metastasis. In this study, we investigated whether melittin inhibits the migration and metastasis of epidermal growth factor (EGF)-induced MDA-MB-231 cells via the suppression of SDF-1α/CXCR4 and Rac1-mediated signaling pathways. Materials and Methods In this experimental study, cells were treated with melittin (0.5-4 μg/ml), and the toxicity of melittin was assessed by the MTT assay. Afterward, the migration assay was conducted to measure the degree of the migration of EGF-induced cells. The western blot technique was performed to analyze the rate of Rac1, p-Rac1, SDF- 1α, and CXCR4 expression in different groups. Results The results demonstrated that melittin markedly suppressed the migration of EGF-induced cells and decreased the expression of p-Rac1, CXCR4, and SDF-1α proteins. ConclusionThe results of the present study suggested that the anti-tumor properties of melittin could be through the blocking of the SDF-1α/CXCR4 signaling pathway, which is beneficial for the reduction of tumor migration and invasion.

Sweet Bee Venom Triggers Multiple Cell Death Pathways or Spurs Acute Cell Rupture According to Its Concentration in THP-1 Monocytic Leukemia Cells.

Sweet bee venom (sBV) contains various pharmacologically active components of bee venom (BV), but it is modified via the removal of the harmful substances found in BV. Thus, sBV has been used for pain relief in Oriental medicine but has only recently been applied for the treatment of various diseases. In this study, we examined the pharmacological effects and immunomodulatory functions of sBV in THP-1 monocytic leukemia cells. Growth inhibition and cell death were observed according to the concentration of sBV. However, the rapid collapse of cell cycle distribution was shown at 20 μg/mL sBV treatment, indicating that sBV led to cell death or acute cell rupture according to concentration. sBV administration activated Caspase-9, PARP1, RIPK1, and RIPK3, suggesting that the pharmacological actions of sBV were associated with induction of apoptosis and necroptosis. On the other hand, sBV or LPS administration increased cytokine expression, including IL-1β, and showed synergistic cell death in combinatory treatment conditions. Moreover, combinatory administration of sBV and LPS induced severe damage or death during egg development. This result implies that sBV exhibits both pharmacological and toxic effects depending on its concentration. Therefore, sBV might be a promising therapeutic approach, but optimal concentration should be considered before treatment.

Photoprotective and therapeutic effects of Apamin, Melittin and Phospholipase A2 on human keratinocyte cell line

The aim of this study is to determine the protective and therapeutic properties of bee venom components Apamin, Melittin and Phospholipase A2 against UV damage on the human keratinocyte cell line. Cosmetic and therapeutic effects of bee venom have been reported in previous studies, but it is not known which components of the venom have the most effect. For this purpose, firstly, an in vitro UV damage model was designed. Components of bee venom were tested at a different concentration. Cell viability, cytotoxicity and apoptotic processes were analyzed on the designed model. As a result, it has been observed that Apamin demonstrated a significant protective effect against UV-induced cell death at all concentrations. Photoprotective effects of Melittin were observed in all concentration time periods and its photoprotective effects were increased as the concentration increased. Our results were indicated that Phospholipase A2 could be used as a photoprotective and phototherapy agent. This study is the first to show the protective and therapeutic properties of bee venom components against UV damage. As a result, it has been shown that these components can be successful photoprotective and phototherapeutic agents against UV-induced damage, but more detailed studies should be conducted to minimize their toxic effects on cells.

Low-dose melittin is safe for intravitreal administration and ameliorates inflammation in an experimental model of uveitis

Uveitis is a group of sight-threatening ocular inflammatory disorders, whose mainstay of therapy is associated with severe adverse events, prompting the investigation of alternative treatments. The peptide melittin (MEL) is the major component of Apis mellifera bee venom and presents anti-inflammatory and antiangiogenic activities, with possible application in ophthalmology. This work aims to investigate the potential of intravitreal MEL in the treatment of ocular diseases involving inflammatory processes, especially uveitis. Safety of MEL was assessed in retinal cells, chick embryo chorioallantoic membranes, and rats. MEL at concentrations safe for intravitreal administration showed an antiangiogenic activity in the chorioallantoic membrane model comparable to bevacizumab, used as positive control. A protective anti-inflammatory effect in retinal cells stimulated with lipopolysaccharide (LPS) was also observed, without toxic effects. Finally, rats with bacille Calmette-Guerin- (BCG) induced uveitis treated with intravitreal MEL showed attenuated disease progression and improvement of clinical, morphological, and functional parameters, in addition to decreased levels of proinflammatory mediators in the posterior segment of the eye. These effects were comparable to the response observed with corticosteroid treatment. Therefore, MEL presents adequate safety profile for intraocular administration and has therapeutic potential as an anti-inflammatory and antiangiogenic agent for ocular diseases.

Anti-cancer effect of melittin-Au25(MHA)18 complexes on human cervical cancer HeLa cells

Melittin (MEL) is the major component of bee venom, which has recently emerged as an attractive candidate for cancer chemotherapy. As a polypeptide, rapid degradation of MEL is considered as one of the most critical challenges in therapeutic applications. In this study, atomically precise gold nanoclusters with 6-mercaptohexanoic acid (MHA) as a thiolate ligand, termed as Au25(MHA)18, were synthesized and employed as the delivery vehicles of MEL to human cervical cancer HeLa cells. The characterization including Zeta potential, UV–Vis spectra, X-ray photoelectron spectroscopy (XPS), and transmission electron microscope (TEM), showed that Au25(MHA)18 nanoclusters can load MEL with high efficiency, resulting in formation of MEL-Au25(MHA)18 complexes. The anti-cancer effect of MEL-Au25(MHA)18 complexes on human cervical cancer HeLa cells in vitro were further evaluated by cell proliferation and cytotoxicity assay, flow cytometry assay, and confocal microscopy imaging. It was found that Au25(MHA)18 nanoclusters protected MEL from degradation leading to long-lasting cytotoxicity on HeLa cells, and maintained the good anti-cancer activity of MEL. The anti-cancer activity of MEL-Au25(MHA)18 complexes on HeLa cells can be well explained through the pore formation by MEL on the surface of cell membrane, which ultimately leading to cytolysis. This work demonstrated the feasibility of atomically precise gold nanoclusters as the delivery vehicles of unstable polypeptide such as MEL, achieving improved efficiency in chemotherapy.

Comparative Study of Antimicrobial Properties of Bee Venom Extracts and Melittins of Honey Bees.

Bee venom (BV), or apitoxin, is a complex substance produced by a gland in the abdominal cavity of bees. The main component of BV is melittin, which is a largely studied substance due to its biological properties. To date, the most well-known bee venom and melittin are derived from domesticated honey bees, while venom and melittin derived from wild honey bees have been under-investigated. Hence, this study primarily reports the antimicrobial activities of bee venom and synthetic melittin derived from four different honey bee species (Apis mellifera, A. cerana, A. dorsata, and A. florea) in Thailand. All the bee venom extracts and melittins showed more robust antibacterial activities against Gram-positive (Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, S. aureus MRSA, and S. epidermidis) than Gram-negative bacteria (Escherichia coli, Klebsiella pneuminiae, and Salmonella typhimurium) or a fungus (Candida albicans), while the synthetic melittins also have antimicrobial activity at higher concentrations than the bee venom extract. Furthermore, the A. cerana venom extract showed the highest activity against the tested bacteria, followed by A. mellifera, A. florea, and A. dorsata. Therefore, A. cerana venom may be further developed for use in medical applications as a potential alternative agent against Gram-positive bacteria and antibiotic-resistant bacteria.