Concentrations Of Bee Venom Research Articles

Exploring bee venom and silver nanoparticles for controlling foulbrood pathogen and enhancing lifespan of honeybees

The beekeeping industry plays a crucial role in local economies, contributing significantly to their growth. However, bee colonies often face the threat of American foulbrood (AFB), a dangerous disease caused by the Gram-positive bacterium Paenibacillus larvae (P. l.). While the antibiotic Tylosin has been suggested as a treatment, its bacterial resistance necessitates the search for more effective alternatives. This investigation focused on evaluating the potential of bee venom (BV) and silver nanoparticles (Ag NPs) as antibacterial agents against AFB. In vitro treatments were conducted using isolated AFB bacterial samples, with various concentrations of BV and Ag NPs (average size: 25nm) applied individually and in combination. The treatments were administered under both light and dark conditions. The viability of the treatments was assessed by monitoring the lifespans of treated bees and evaluating the treatment's efficiency within bee populations. Promising results were obtained with the use of Ag NPs, which effectively inhibited the progression of AFB. Moreover, the combination of BV and Ag NPs, known as bee venom/silver nanocomposites (BV/Ag NCs), significantly extended the natural lifespan of bees from 27 to 40 days. Notably, oral administration of BV in varying concentrations (1.53, 3.12, and 6.25 mg/mL) through sugary syrup doubled the bees' lifespan compared to the control group. The study established a significant correlation between the concentration of each treatment and the extent of bacterial inhibition. BV/Ag NCs demonstrated 1.4 times greater bactericidal efficiency under photo-stimulation with visible light compared to darkness, suggesting that light exposure enhances the effectiveness of BV/Ag NCs. The combination of BV and Ag NPs demonstrated enhanced antibacterial efficacy and prolonged honeybee lifespan. These results offer insights that can contribute to the development of safer and more efficient antibacterial agents for maintaining honeybee health.

Bee venom: A potential natural alternative to conventional preservatives for prolonging the shelf-life of soft cheese ‘Talaga’

The study aims to explore bee venom (honey-BV) as a potential natural preservative for "Tallaga" soft cheese. Characterization of the active compounds in honey-BV was conducted via chromatographic analyses. Antimicrobial efficacy against pathogenic bacteria and fungi was evaluated, and minimum inhibitory concentration (MIC) was determined. Subsequently, honey-BV was applied to Tallaga cheese at 15 mg/g concentrations. The main active ingredients identified in bee venom were apamin (2%) and melittin (48.7%). Both concentrations of bee venom (100 and 200 mg/mL) exhibited significant antifungal and antibacterial properties against tested organisms, with MIC values varied from 0.2 to 0.5 mg/mL for bacteria to 3–13 mg/mL for fungi. Application of honey-BV in Tallaga cheese resulted in complete elimination of Staphylococcal populations after 2 weeks of cold storage, with no detectable growth of molds or yeasts throughout the storage period. Additionally, a steady decrease in aerobic plate count was observed over time. In summary, honey-BV holds promise as a natural preservative for soft cheese, however, more investigation is required to optimize the concentration for economic viability, taking into account health benefits and safety considerations.

The Effect of Different Concentrations of Bee Venom on Kidney Tissue of Albino Male Rats Rattus

In this study, 60 males of albino rats (Rattus rattus) were tested to study the effect of BV on kidney tissue at two doses of 10 and 40 µg/kg and two times after 10 and 15 days. The sample included 40 rats divided into two groups; 20 rats for each group. These groups were injected intraperitoneally according to the mentioned periods and were considered as a control group. The results exhibited renal tubule dilation and slight atrophy of glomerular tuft in the kidneys of rats treated with 10 µg/kg for 10 days compared to kidneys in the control treatment. Furthermore, 10 µg/kg treatment for 15 days has caused renal tubule dilation and degeneration with cytoplasmic vacuolation. Our findings also showed a slight atrophy of the glomerular tuft as well as a reduction in the number of glomeruli in this subcapsular area. The results also indicate regeneration of kidney tubules in rats given 40 µg/kg for 10 days. Meanwhile, sections of the kidney for rats that were given 40 µg/kg for 15 days exhibited a slight atrophy of glomerular tuft hypertrophied tubular epithelial cells.

Antibacterial Activity of Honeybee Venom Against Pathogenic Bacteria in Comparison with Common Antibiotics

Antibiotic resistance has dramatically spread in recent decades and has become a serious problem in modern medicine. Honeybee venom or bee venom (BV) has anticancer, anti-inflammation, and antimicrobial properties. This study aimed to evaluate the influence of BV on certain pathogenic bacteria. The effects of different concentrations of BV against Klebsiella pneumonia, Pseudomonas aeruginosa, and Staphylococcus aureus were evaluated by disk diffusion method (inhibition zone, IZ), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Additionally, the antibacterial activity of BV was compared with that of ampicillin, penicillin, and tetracycline. The results indicated that different concentrations of BV had an inhibitory effect on the pathogen species. The MIC and MBC of BV were 18 and 24 μg/mL for K. pneumonia, respectively, 38 and 42 μg/mL for P. aeruginosa, respectively, and 21 and 31 μg/mL for S. aureus, respectively. Among the bacterial species tested, BV was the most effective against K. pneumonia. Meanwhile, P. aeruginosa was the most resistant against BV. The comparison revealed that 100 μg/mL BV had a greater effect on IZ against P. aeruginosa and K. pneumonia compared with evaluated common antibiotics (p < 0.05). This study showed that BV demonstrated antibacterial effects. Precise toxicology examinations are required for the development of new antibiotics.

Pharmacokinetic improvement provided by microneedle patch in delivering bee venom, a case study in combating scopolamine-induced neurodegeneration in mouse model

Much research has shown Bee venom to be an effective neuroprotective agent. However, the usual transdermal injection of bee venom poses many pharmacokinetic disadvantages. Here, we compared the administration of bee venom via subcutaneous injection (SC) and via Microneedle patch (MN). Both administrated routes produce significant recovery effects, however: the MN significantly prolongs the bio-significant-and-yet-lower concentration of bee venom in mice bodies. In contrast, SC could produce only a short period of much higher bee venom levels in the blood and brain. We also see that due to the concentration-response-curve of bee venom (represented by melittin): mice bodies do not require much higher bee venom concentration (seen in the SC group) to produce a much more significant neuroprotective effect (than seen in those treated with the MN method). Therefore, a MN could maintain bee venom levels in mice bodies at lower-yet-more-efficient concentrations. This is important, as bee venom can cause more adverse effects and pain sensations, at higher concentrations. For the first time, we confirmed that the pharmacokinetic advantages of MN delivered bee venom also guarantee a holistic neuroprotection effect (which was shown by SC delivered bee venom in previous research). This was proven via the results of the water maze experiments for long-term learning memory assessment and protein analysis of key neuronal regulatory proteins: BDNF, p-CREB, iNOS, and mArhR 1. In conclusion, for situations where we ought to administrate drugs at a more downward amount, such as bee venom, MN can keep the therapeutic concentrations at a lower, yet interestingly, more-efficient level.

Histopathological Study of Bee Venom with Different Concentrations in Laboratory Mice

Bee venom (BV) of Apis mellifer L has recently been utilized as a traditional medicine for treating a variety of medical conditions. When mice were given different concentrations of bee venom, it was found to be effective in repairing some histopathological changes. Then, when applying BV as a treatment material for some disorders, as indicated by the amount of damage to the liver and kidney tissues. The animals were randomly divided into 7 groups. Six of which were treated with BV extraction, and one group was designated as the control group, was treated with distilled water. Mice were injected intraperitoneally by 0.2ml of BV extraction in concentrations (1000, 750, 500, 350, 300, and 250) μg/ml. In some cases, histopathological studies revealed mild to moderate alterations in the liver and renal tissues, characterized by congestion, acute cell swelling, and focal coagulated necrosis. Atherosclerotic changes in the aorta and some arteries were found in two groups. Whereas several mild degenerative changes were observed in hepatic cells of one group. In conclusion, bee venom administered to groups in different concentrations revealed hepatic and renal complications at histological investigations of hematoxylin and eosin-stained sections of liver and kidney section.

In-vitro Investigation of the Effect of Bee Venom on Schistosoma mansoni Eggs

Schistosomiasis (Bilharziasis) is a fatal parasitic disease caused by parasitic worms with the genus Schistosoma. The release of Schistosoma eggs in running fresh water contributes to completing its life cycle. Therefore, finding a suitable drug having ovicidal activity towards eggs is crucial. Here, we investigate the in-vitro effect of bee venom (the venom of Apis millifera) on the eggs of Schistosoma mansoni (S. mansoni). The eggs were incubated with different concentrations of bee venom and then the percent mortality, hatchability and morphology of the eggs were observed. It was found that bee venom causes morphological alterations for S. mansoni eggs. In addition, there is a critical concentration (100 µg/mL) at which bee venom leads to the lowest mortality and the highest hatchability percent. Below or above this threshold, the mortality increases and the hatchability decreases. Moreover, bee venom was proven to have a lethal effect on S. mansoni miracidia.

Honey Bee Dry Venom Reduces Hepatitis B Virus Surface Antigen Secretion in PLC/PRF/5 Cell Line

Background and Aims: Currently, many efforts are directed toward functional Hepatitis B virus (HBV) treatment. This is achievable by suppression of HBV surface antigen (HBsAg) secretion. In this regard, use of natural products has been the areas of interest by scientific communities. Materials and Methods: Dried Honey Bee venom was extracted for assessing its anti-HBsAg secretion potential. Hepatoma cell-derived PLC/PRF/5 was propagated in complete medium. The cell line was treated by a serial dilution of Bee venom. Cell cytotoxicity (IC50) was measured by MTT colorimetric assay at three post-treatment times. HBsAg secretion was evaluated from PLC/PRF/5 supernatant treated by under-cytotoxic concentrations of Bee venom by using enzyme-linked immunosorbent assay. Results: The results indicated that dried Bee venom extract is able to reduce secretion of HBsAg from the cell line with Selectivity Index (SI) of eight. Reduced levels of HBsAg were in dose-dependent manner and it was in its lower concentrations at 8 ppm after 12 hr post treatment. The IC50 was observed to be 63.78 ppm. Conclusions: The Bee venom has anti-HBV activity. The way we used under-cytotoxic concentration of Bee venom, the HBsAg secretion was restored after 24 hr post treatment. Furthermore, mechanism of action of Bee venom in reducing HBsAg level needs to be further investigated.

Assessment of hemolytic activity of bee venom against some physicochemical factors

Abstract Bee venom (BV) is a biotoxin with biologically active peptides which have cell lysis and hemolytic activity properties. These properties can be affected under different storage conditions or during the production process. In present study, we investigated effects of a number of physicochemical factors, including temperature, pH, UV radiation, ultrasound waves and storage time on hemolytic activity of BV. Maximum absorption and melting temperature of BV solution were obtained as 280 nm and ~70 °C, respectively. Cell hemolysis 50 (CH50) -concentration of BV that can lyse 50% of red blood cells- was determined as 0.94 μg/ml at ambient temperature. CH50 was shown not to be importantly varied at temperature up to 60 °C, pH value 2 to 13 and under UV/ ultrasound radiation. Storage at −20, 6 and 25 °C for 6 months made about 2.5, 35 and 1000 times increase in CH50. From the results, it may be concluded that BV is a relatively resistant hemolytic agent and can be used in a variety of laboratory research and product manufacturing methods.

Ultrastructural variability of mitochondrial cristae induced in vitro by bee (Apis mellifera) venom and its derivatives, melittin and phospholipase A2, in isolated rat adrenocortical mitochondria

We tested the ability of bee venom (BV), melittin (Mlt), and phospholipase A2 (PLA) – used in 5 concentrations each (5, 10, 15, 20 and 40 μg/100 μl) – to promote ultrastructural changes and reorganization of cristae in vitro in mitochondria isolated from rat adrenal cortex after a protocol optimized by us. Thus, apart from two control grups (CI and CS), in which the mitochondria were suspended into saline buffer and isolation medium respectively, 15 more groups of mitochondria were constituted, corresponding to the five different doses of the three substance tested (BV5 to M40; M5 to M40 and P5 to P40). The ultrastructural effects were quantified on transmission electron micrographs using a morphometry software. Values of 84.49 nm and 95.45 nm were calculated for median diameters of mitochondrial cristae in two control groups. Large and very large vesicular cristae, many with 2 or 3 membranes, were generated depending on dose among normal cristae in all treated groups. In the BV and Mlt treated groups, after an initial increase (up to 127.27 nm in V15 group and 151.2 nm in M10 group) due to stimulation of cristae fusion, the cristae diameter diminished as the doses increased, mainly by the collapse of the cristae. In the PLA treated groups, the cristae diameter increased continuously from 83.84 nm to 136.01 nm, by stimulated fusion of cristae, only the two largest doses promoting the collapse of cristae in some mitochondria. The highest percentage of abnormal cristae was found in the Mlt treated groups and next in BV treated groups. All substances tested produced pronounced ultrastructural variability of mitochondrial cristae in vitro: they also changed (depending on dose) mitochondrial shapes, generated matrix debris and the highest concentrations of BV and Mlt were responsible for mitochondrial breakdown. These ultrastructural alterations of mitochondrial criste in the presence of the BV molecules suggest a reduced capacity of adrenocortical mitochondria to synthetize steroid hormones consequently to BV envenomations and partially explain the toxic effects of the BV.

Honey bee venom combined with 1,25-dihydroxyvitamin D3as a highly efficient inducer of differentiation in human acute myeloid leukemia cells.

Most cancer cells exhibit a defect in their capacity to mature into nonreplicating adult cells and existing in a highly proliferating state. Differentiation therapy by agents such as 1,25-dihydroxyvitamin D3(1,25-(OH)2 VD3) represents a useful approach for the treatment of cancer including acute myeloid leukemia. Human myeloid leukemia cell lines are induced to terminal differentiation into monocyte lineage by 1,25-(OH)2 VD3. However, usage of these findings in the clinical trials is limited by calcemic effects of 1,25-(OH)2 VD3. Attempts to overcome this problem have focused on a combination of low concentrations 1,25-(OH)2 VD3 with other compounds to induce differentiation of HL-60 cells. In this study, the effect of honey bee venom (BV) and 1,25-(OH)2 VD3, individually and in combination, on proliferation and differentiation of human myeloid leukemia HL-60 cells were assayed. In this in vitro study, toxic and nontoxic concentrations of BV and 1,25-(OH)2 VD3 were tested using Trypan blue stained cell counting and (3[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. In addition, differentiation of cells was assayed using a Wright-Giemsa staining and nitroblue tetrazolium reduction test. Data were analyzed by a one-way analysis of the variance test using SPSS software. Our findings showed that both the BV and 1,25-(OH)2 VD3, in a dose and time-dependent manner, caused cell death at high concentrations and inhibited cell proliferation at lower concentrations. About 5 nM of 1,25-(OH)2 VD3 induced differentiation of HL-60 cells to monocytes after 72 h. 2.5 μg/ml of BV suppressed proliferation of HL-60 cells but had not any effects on their differentiation, whereas in combination with 5 nM of 1,25-(OH)2 VD3, it enhanced antiproliferative and differentiation potency of 1,25-(OH)2 VD3. These results indicate that BV potentiates the 1,25-(OH)2 VD3-induced HL-60 cell differentiation into monocytes.

Evaluation of the antiviral effect of bee venom on rabies virus

It is an interesting thing to known the effect of natural matter as bee venom as antiviral agent and to any extent it couldbe used in case of experimental rabies infection. In vitro study revealed that different concentrations of bee venom (startedfrom the original concentration “1mg/ml” up to 1:1000) did not show any cell growth retarders or cellular changesshowing normal growth rate and normal cell shape. 1mg/ml and 100μgm/ml of bee venom were able to inhibit thereplication of 100 TCID50 of rabies virus (ERA strain) in using baby hamster kidney BHK cells while 10 and 1μgm/mlwere negative. In vivo study showed that mice received rabies immune globulin and BV were able to withstand the rabisinfection when the they were administrated on the o, 1st, 2nd and 3rd day post infection showing protection rate of 90 and80% respectively but those mice received the treatment on the following days did not survive the infection and showedparalysis of the hind limbs by the 4th day and died by the 6-7th day post infection. It could be concluded that bee venomcould be used in case of rabies infection when administrated on the suitable time post exposure

Cytotoxic and Pro-Apoptotic Effects of Honey Bee Venom and Chrysin on Human Ovarian Cancer Cells

Background: The anti-cancer effects of honey bee venom (BV) and chrysin might open a new window for treatment of chemo-resistant cancers. This study was designed to evaluate cytotoxic and pro-apoptotic effects of BV and chrysin on A2780cp cistplatin- resistant human ovarian cancer cells. Methods: As per the study objectives, A2780cp cells were categorized to 4 groups: 3 experiment groups (treated either with BV or chrysin or BV + chrysin) and 1 control group (untreated cells). Experiment group cells were cultured and treated by different concentrations of BV and chrysin for 24 hours. Then, experiment and control cells were studied with MTT assay, Annexin V-FITC, DAPI and Acridine Orange / Propidium Iodide statining, flow cytometry, caspase-3 and -9 assay, measurement of intracellular level of reactive oxygen species (ROS) and RT-PCR. Results: MTT assay showed that 8 I¼g/mL BV, 40 µg/ml chrysin and 6 + 15 I¼g/mL BV + chrysin co-treatment induced 50 cell death on A2780cp cells compared with controls (P < 0.001). Morphological observations by inverted and fluorescent microscopy revealed ROS generation and apoptotic cell death under exposure to BV or chrysin or BV + chrysin co-treatment. Caspase-3 and -9 assay demonstrated that BV and chrysin triggered apoptosis through intrinsic pathway and RT-PCR demonstrated down-regulation of Bcl-2. Conclusion: Honey bee venom and chrysin are effective for destroying chemoresistant ovarian cancer cells through activation of intrinsic apoptosis, which propose them as potential candidates to be used in development of improved chemotherapeutic agents in the future.

Immunomodulatory effects of bee venom in human synovial fibroblast cell line.

As in Iranian traditional medicine, bee venom (BV) is a promising treatment for the rheumatoid arthritis (RA) which is considered as a problematic human chronic inflammatory disease in the present time. Smoking is considered to be a major risk factor in RA onset and severity. The main aim of this study is to investigate the effects of BV on cigarette smoke-induced inflammatory response in fibroblast-like synoviocytes (FLS). Cytotoxicity of cigarette smoke condensate (CSC) and bee venom were determined by the tetrazolium (MTT) method in cultured synovial fibroblastes. The expression of interleukin-1β and sirtuin1 mRNA were analyzed by SYBR green real-time quantitative PCR. Differences between the mean values of treated and untreated groups were assessed by student t-test. Based on MTT assay, CSC and BV did not exert any significant cytotoxic effects up to 40 µg/mL and 10 µg/mL, respectively. Our results showed that interleukin-1β mRNA level was significantly up-regulated by CSC treatments in LPS-stimulated synoviocytes in a dose-dependent manner. Conversely, the expressions of IL-1β and Sirt1 were up-regulated even in lower concentrations of BV and attenuated at higher concentrations. Also, BV attenuated the CSC-induced and LPS-induced inflammatory responses in synovial fibroblasts. Our results support the epidemiological studies indicating pro-inflammatory effects of CSC and anti-inflammatory effects of BV on FLS cell line.

Bee Venom at Different Concentrations Modulates the Aeroallergen-Induced Activation of Nasal Polyp Epithelial Cells

Bee venom (BV) has long been used as an oriental traditional medicine for the control of pain and inflammation. However, BV’s anti-inflammatory mechanisms remain unclear. This study aimed to clarify the potential clinical efficacy of BV concerning the anti-inflammatory effect on nasal epithelial cell inflammation. Nasal polyp epithelial cells were obtained from patients. Cells were exposed to Alternaria alternata, Aspergillus nigra, Dermatophagoides pteronyssinus, Dermatophagoides farina and lipopolysaccharide with or without various concentrations of BV. Interleukin (IL)-6, IL-8, and granulocyte macrophage colony-stimulating factor were measured to determine the activation of epithelial cells. Nuclear factor-ĸB (NF-ĸB) and activator protein 1 expression and activity were determined with Western blot analysis and ELISA. Cytotoxicity of BV was measured using a CellTiter-96® aqueous cell proliferation assay kit. Cell survival was significantly decreased at BV concentrations exceeding 5 µg/ml. Fungi-induced cytokine production was more effectively inhibited by BV than house dust mite. Alternaria enhanced NF-ĸB expression, which was strongly inhibited by BV. BV appears to be relatively safe, and is of potential value for the treatment of airway inflammation and/or immunologic diseases.

A sensitive enzyme-linked immunosorbent assay for evaluating the concentration of bee venom in rat plasma.

A simple and reproducible enzyme-linked immunosorbent assay (ELISA) was developed to determine the concentration of bee venom in rat plasma. The intra- and inter-assay coefficients of variation for the ELISA were less then 3% between 0.1 and 1,000 ng mL(-1) venom, and the sensitivity of the detection was 0.1 ng mL(-1). Total recovery of the bee venom added to rat plasma was determined. Using this ELISA, serum levels of bee venom were easily determined. The rats were administered a single intravenous injection or oral dose of bee venom (1 mg kg(-1) of body weight). The bioavailability of the bee venom under the two administrations was compared using pharmacokinetic parameters. Results showed that intravenous administration of bee venom produced high plasma concentrations with a short half-life. The area under the curve for oral administration was 10 times lower than for intravenous administration. This loss of bee venom may be due to the degradation that occurs in the enzymatic and acidic environment of the gastrointestinal tract.

Effect of Bee Venom on Transforming Growth Factor–β1-Treated Hepatocytes

Bee venom (BV) has been used as treatment against a wide variety of ailments, including inflammatory diseases. Various studies have demonstrated anti-inflammatory and anticancer effects of BV. Transforming growth factor (TGF)-beta1 induces hepatocyte apoptosis via the mitochondrial permeability transition. However, there is no evidence or information regarding the antiapoptotic effect of BV on hepatocytes. The authors investigated the antiapoptotic effect of BV on TGF-beta1-treated hepatocytes. The results showed significant protection from DNA damage by BV treatment compared to corresponding TGF-beta1-treated hepatocytes without BV. BV suppressed TGF-beta1-induced activation of the bcl-2 family and caspase family of proteins, which resulted in inhibition of poly ADP-ribose polymerase (PARP) cleavage. Furthermore, BV is not cytotoxic in the low concentrations used in this study. Low concentrations of BV potently suppress the apoptotic response in TGF-beta1-treated hepatocytes; therefore, BV may have therapeutic potential for the treatment of liver diseases.

Wound healing and anti-inflammatory activities of bee venom-chitosan blend films

Bee venom (BV) therapy is the therapeutic application of honey bee venom for the treatment of various diseases. In order to apply BV to the skin, as a topical formulation, chitosan (Chit) films were fabricated. Bee venom could be loaded at 6% w/w of polymer in the films. The morphology and mechanical properties, including bioadhesive properties, surface pH, primary skin irritation test, microbial penetration, tensile strength, percentage of elongation and swelling ratio, were evaluated. According to the mechanical properties of the films, 6% bee venom-chitosan (6% BV-Chit) films were superior to both chitosan free film (Chit-F) and other films containing lower concentrations of BV. Accordingly, chitosan films containing 6% BV were the subject of further pharmacological and biological tests. The wound healing activities of Chit-F and 6% BV-Chit films were evaluated using excision, round section, full thickness skin wound model in rats. In addition, the anti-inflammatory effects of Chit-F and 6% BV-Chit films were studied in rats using the rat paw edema thickness method. Furthermore, serum prostaglandin E2 (PGE2) was determined to investigate the possible mechanism for the anti-inflammatory activity of this topical formulation. The results show that both Chit-F and 6% BV- Chit films accelerated the wound healing compared to untreated rats. As for the anti-inflammatory effects, 6% BV-Chit films had greater potency compared to that of Chit-F and this effect was comparable to that of the standard NSAI, indomethacin. Moreover, the elevated serum PGE2 was significantly reduced in a descending order as follows: indomethacin > 6% BV-Chit > Chit-F. These results suggest that the combination of wound healing ability of chitosan together with the anti-inflammatory activity of BV in one topical formulation provide a promising therapy for rapid complete sterile wound healing, in addition to an anti-inflammatory activity for topical inflammatory lesions.

Apis Mellifera Venom and Melittin Block neither NF-κB-p50-DNA Interactions nor the Activation of NF-κB, Instead They Activate the Transcription of Proinflammatory Genes and the Release of Reactive Oxygen Intermediates

Many alternative treatment approaches, originating from Asia, are becoming increasingly popular in the Western hemisphere. Recently, an article published in a renowned journal reported that venom of apis mellifera (bee venom (BV)) and melittin mediate immune-modulating effects by blocking the activation of the transcription factor NF-kappaB. Such a modus operandi would corroborate the many claims of beneficial effects of BV treatment and give immediate credit to this form of therapy. Fibroblast-like synoviocytes from rheumatoid arthritis patients and dermal fibroblast cells and white blood cells from healthy volunteers were used to study the effects of BV and melittin on the activation of NF-kappaB and a series of genes that are markers of inflammation. EMSAs demonstrate that neither BV nor melittin blocked IL-1beta-induced NF-kappaB activation; neither did they affect phosphorylation or degradation of IkappaB. Contrary to published data, even high concentrations of BV and melittin were without any effect on NF-kappaB-p50-DNA interactions. More importantly, in fibroblast-like synoviocytes, but also in dermal fibroblasts as well as in mononuclear cells exposed to BV or melittin, mRNA levels of several proinflammatory genes are significantly increased, and Western blot data show elevated cyclooxygenase-2 protein levels. Furthermore, exposure to BV higher than 10 mug/ml resulted in disintegration of all cell types tested. In addition, large quantities of oxygen radicals are produced in a dose-dependent manner in leukocytes exposed to BV. Taken together, data presented in this work do not corroborate an earlier report regarding the effectiveness of BV as an inhibitor of the transcription factor NF-kappaB.

족삼리(足三里) 봉독약침자극(蜂毒藥鍼刺戟)이 척수내(脊髓內) Fos 양성반응(陽性反應) 신경세포(神經細胞)의 활성(活性)에 미치는 영향(影響)

This study was designed to evaluate the analgesic effect of bee venom (BV) Acupuncture into different treatment points, Chok-samni (ST36) and blank loci of the gluteal muscle and back. We investigated neuronal activity in the spinal cord using the Fos immunohistochemical technique according to the pretreatment with different concentrations of BV, thirty minutes before the formalin injection. The results were summarized as follows: 1. The number of Fos-like immunoreactive (Fos-LI) neurons in L2 segment of the saline-formalin treated group was significantly increased in NECK and VENT of the spinal cord as compared with that of the room control group. However, there was no significant change in the number of the Fos-LI neurons in L2 segment of the BV-formalin treated group as compared with that of the room control group. 2. The number of Fos-LI neurons in L3-5 segment of the saline-formalin group was significantly increased in all the regions of 142 the spinal cord as compared with that of the room control group. However, the Fos-LI neurons in L3-5 segment of the BV-formalin treated group was dramatically decreased in all the regions of the spinal cord as compared with that of the saline-formalin group. Therefore, these results indicated that the BV acupuncture suppressed the nociceptive neuronal activities in L3-5 of the spinal cord induced by formalin injection. 3. There was a strong positive correlation between the formalin-induced pain behavior and the number of the Fos-LI neurons in L3-5 segment.