• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.173-177
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• 2009

The in vitro antibacterial activities of honeybee(Apis mellifera. L) venom collected by a bee venom collector were investigated against several bacteria including antibiotic-susceptible and resistant Propionibacterium acnes. Honeybee venom was prepared with different concentrations and they showed strong antibacterial activites. Honeybee venom inhibited the growth of the tested antibiotic-resistant P. acnes at the concentration of 1 mg/ml. The inhibitory activities of the honeybee venom showed time-dependent manner. Honeybee venom did not influence the viability of human dermal fibroblast at the high concentration of less than 10 mg/ml. From these results, we expect that honeybee venom has strong antibacterial activities and has advantage for treating cure.

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.154-165
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• 2003

Objective : to research the trend of the study related to Bee venom and o establish the hereafter direction for the study on Bee Venom therapy. Methods : We reviewed the domestic papers published last ten years(1992-2001). Results: 1.We have searched 53 papers in 7 journals and the pattern of study was as follow: the experimental studies were 33, the clinical studies were 10 and the reviewed studies were 10. 2. The experimental studies were 2 papers of analysis of Bee Venom, 3 papers of safety assessment, 1 paper on production of antibody against Bee Venom and 26 paper of safety assessment. 3. Bee Venom used in studies was made in Korea, China and U.S.A.. There were differences of component and effect according to the place of production. 4. There were the experimental studies of LD50 in mouse, acute toxicity, local irritation test, antigenicity and pyrogen test of Bee Venom. Conclusions : We need more studies of unification of term about Bee Venom, difference according to the place of production, clinical safety and effects.

• Journal of Acupuncture Research
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• v.30 no.1
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• pp.57-70
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• 2013

This study was to investigated the effects of the bee venom on inhibition of cell growth via upregulation of death receptor expression in the A549 human lung cancer cells. Bee venom(1-5 ${\mu}g$/ml) inhibited the growth of A549 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of TNFR1, Fas, death receptors(DR) 3, 4 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, -9 and Bax was concomitantly increased, but the expression of Bcl-2, NF-${\kappa}B$ were inhibited by treatment with bee venom in A549 cells. Moreover, deletion of DR3, DR4 by small interfering RNA significantly reversed bee venom-induced cell growth inhibitory effect, whereas Apo3L strengthened anti-proliferative effect of bee venom through enhancement of DR3 expression. These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.2
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• pp.27-40
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• 2010

Background and Objective : Increasing interest in anti-aging and anti-wrinkling agents for the skin has triggered the recent outflow of researches and studies in this field. This study was designed to investigate the effects of bee venom on skin wrinkling and skin aging by testing the skin wrinkling, skin elasticity, trans-epidermal water loss (TEWL), free radical level, anti-oxidative agent level, and skin tissue after infusion of bee venom on hairless mouse. Materials and Methods : Fifteen hairless mice aged between 36~40 weeks were divided randomly into 3 Group; the Bee Venom Syringe Group, the Bee Venom Needle Group, and the control group. The Bee Venom Syringe Group were injected subcutaneously with bee venom (0.1cc in total) using an insulin syringe on three spots in the lumbar spine (one spot on the center and two spots 1~2cm to the side bilaterally). The Bee Venom Needle Group were pricked with bee venom-smeared acupuncture needles on three longitudinal spots in the lumbar spine each 1cm apart, after which the needles were removed 10 minutes later. The Control Group did not receive any form of intervention. All procedures took place thrice a week for four weeks, during which the mice were allowed free access to water and fodder. The mice were measured and compared in the weight, skin wrinkling scale, skin elasticity, and TEWL before and after the experiment. After the experiment, blood samples were taken to measure the free radical and anti-oxidative agent level, and the skin tissue was sliced for examination. Data was analyzed using the SPSS program (ver 12.0). The ANOVA analysis was used to compare and contrast the three groups, and t-test for paired samples was used to evaluate skin-wrinkling before and after experiment. The cut-off p-value of significance was set at p<0.05. Results : 1. Administration of bee venom did not cause serious weight loss or gain. 2. Compared to the control group, the Bee Venom Syringe Group and the Bee Venom Needle Group both showed a decrease in skin wrinkling scale after intervention. Especially, the Bee Venom Syringe Group showed a significant decrease (p<0.05). 3. Compared to the control group, the Bee Venom Syringe Group and the Bee Venom Needle Group both showed an increase in skin elasticity. Especially, the Bee Venom Syringe Group showed a significant increase (p<0.05). 4. No significant change in TEWL was found in the mice in all the three groups before and after experiment. 5. Free radical level was normal in all 15 mice in all the three groups, and anti-oxidative agent was not significantly different across the three groups. 6. The Bee Venom Syringe Group, the Bee Venom Needle Group, and the control group did not show any significant difference in the thickness of epidermis and dermis, infiltration of inflammatory cells, and skin wrinkling. The epidermis layer was relatively better preserved in the Bee Venom Syringe Group as compared to the Bee Venom Needle Group and the control group. Conclusion : Direct injection of bee venom on the hairless mouse using a syringe was found to improve wrinkling of the skin and increase skin elasticity but did not show effectiveness on skin dryness due to water loss. The bee venom appears to have suppressive effects on skin wrinkling, one of the symptoms of skin aging, through a process independent of suppression of free radicals or increase of anti-oxidative agent.

• Journal of Acupuncture Research
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• v.33 no.2
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• pp.1-9
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• 2016

Objectives : I investigated whether snake venom can synergistically strengthen the cytotoxic effects of NK-92 cells, and enhance the inhibition of the growth of lung cancer cells including NCI-H358 through the induction of death receptor dependent extrinsic apoptosis. Methods : Snake venom toxin inhibited cell growth of NCI-H358 Cells and exerted non influence on NK-92 cell viability. Moreover, when they were co-cultured with NK cells and concomitantly treated with $4{\mu}g/m{\ell}$ of snake venom toxin, more influence was exerted on the inhibition of growth of NCI-H358 cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2 and DR3 and in NCI-H358 lung cancer cells was significantly increased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells alone. Coincidentally, Bax, caspase-3 and caspase-8 - expressions of pro-apoptotic proteins in the extrinsic apoptosis pathway, demonstrated significant increase. However, in anti-apoptotic NF-${\kappa}B$ activities, activity of the signal molecule was significantly decreased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells or snake venom toxin treated by NCIH358 alone. Meanwhile, in terms of NO generation, there is a significant increase, in co-culture of NK-92 cells with NCI-H358 cells as well as the co-culture of NK-92 cells and concomitant treatment of $4{\mu}g/m{\ell}$ of snake venom toxin. However, no synergistic increase of NO generation was shown in co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells with NCI-H358 cells. Conclusion : Consequently, this data provides that snake venom toxin could be useful candidate compounds to suppress lung cancer growth along with the cytotoxic effect of NK-92 cells through extrinsic apoptosis.

• Journal of Acupuncture Research
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• v.19 no.3
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• pp.41-50
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• 2002

Objective : To study anti-inflammatory, analgesic effect and molecular biological mechanism of honey bee venom for aqua-acupuncture, human mast cell line(HMC-1) and human glioma cell line(HS683) were treated with bee venom. Methods : Cell viability of bee venom was tested by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) asssay. To explore whether anti-inflammatory, analgesic effects of bee venom are associated with the control of gene expression, quantitative RT-PCR analysis of inflammation and pain related genes was performed. Results : The MTT assay demonstrated that cell viability was not decreased by treatment with 10-9 ug/ml bee venom in comparison with 10-2, 10-3, 10-4, 10-5, 10-6, 10-7, 10-8, 10-9, 10-10 and 10-11 ug/ml. sPLA2 and COX-l were down-regulated by treatment with 10-9 ug/ml bee venom in HS683 Cell line in comparison with control. COX-2 was up-regulated by treatment with 10-9 ug/ml bee venom in HS683 Cell line and HSP-2 was up-regulated by treatment with 10-9 ug/ml bee venom in HMC-1 Cell line in comparison with control. sPLA2, COX-1 and COX-2 showed no significant regulation in HMC-1 Cell line and cPLA2 also showed no significant regulation in both HMC-l and HS683 Cell line between control and bee venom treated group.

• Korean Journal of Veterinary Service
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• v.41 no.3
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• pp.171-177
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• 2018

Purified bee venom was collected from colonies of honeybees (Apis mellifera L.) using a bee venom collector under sterile conditions and then purified under strict laboratory conditions. Purified bee venom contained $63.9{\pm}5.4%$ melittin, $10.9{\pm}1.6%$ phospholipase A2, and $2.3{\pm}0.3%$ apamin. Purified bee venom has various anti-bacterial, anti-inflammatory and immunostimulating effects. In this study, we evaluated purified bee venom which are mammary gland cells, MAC-T cells are used to increase the synthesis of milk protein. Purified bee venom promoted the proliferation of MAC-T cells at concentrations below $1{\mu}g/mL$, but cytotoxicity at $10{\mu}g/mL$ and above. As a result of the increase in the synthesis of ${\beta}-casein$, a milk protein after treatment with MAC-T cells at a concentration of the bee venom without cytotoxicity, the ${\beta}-casein$ content in the cell culture was increased when treated at a concentration of 1 ng/mL or more. In addition, it was confirmed that purified bee venom significantly increased the expression of bovine ${\beta}-casein$ (bCSNB) mRNA, a ${\beta}-casein$ synthesis gene, at a concentration of 1 ng/mL or more. These results suggest that purified bee venom can be used to increase the production of livestock by ultimately increasing the expression of milk protein.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.3-8
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• 2000

1. Definition : Bee-venom therapy does not involve actual bee-stings: it is a treatment method with acquired bee-venom extract through the electric stimulus on the bee, It is injected subcutaneusly on the acupuncture point after refining, according to the diagnosis of constitution and disease. 2. History : Around 2000 B.C., records that Bee-venom was used for therapy were written in the medical book of Babylonia and Papirus of ancient Egypt. Hippocrates, who is called the father of Medicine, said that Bee-venom is Arcanum, which means mysteric medicine. In Oriental medicine, B.C. 200, there was a clinical record that the meat suspended in front of the bee house on the tree in order to get bee-venom, was attached on the lesion. 3. Mechanism of Action : There are two aspects: 1) The effect of stimulating acupunture point It is similar to the chemical moxa. I think that there are several methods of stimulating the acupuncture point： For example, a simple needle is a mechanical stimulus, Moxa is a heating stimulus and electric and Raser acupunture etc. And another stimulus: in the ancient orient, a chemical stimulus called Chungu(Tianjiu), is attached to the lesions by using grinded insects (ex. Mylaris phalerate PALL.) which have toxin. So Bee venom therapy is similar to this. 2) The effect of biochemical ingredients Bee venom consists of 40 kinds of ingredients. For example, me Iii tin, Apamin, Pospholipase A2, MCD peptide, Adolapin and so on. They have effects which have been proven through experimentation l) tonifying mechanism of the body through increasing hormon secretion 2) tonifying immune system through proliferation of WBC, lymphocytes, macrophage 3) anti-inflammatory reaction Therefore Bee venom therapy is the representative 3rd Medicine, which combined East & West medicine. 4. Application of disease : L.B.P and HIVD, O.A, R.A, degenerative arthritis, shoulder pain and other pain diseases. 5. Therapic methods : According to constitution and disease, proper concentration of bee venom is injected on acupunture point, 2 times a week. Generally one term is consisted of 15times. 6. Contraindication : Heart disease, TBc, DM, kidney disease(nephritis), pregnancy, woman in menstruation 3-4 persons per 100,000 persons may have severe allergic reaction.

• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.149-158
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• 2003

Objective : The purpose of this study was to investigate the effect of Bee Venom on the lipopolysaccharide, sodium nitroprusside and hydrogen peroxide induced expression phospholipase $A_2$ and calcium concentration in RAW 264.7 cells, a murine macrophage cell line. Method : The expression of phospholipase $A_2$ was determined by western blotting with corresponding antibodies, and the generation of intracellular calcium concentration was investigated by delta scan system in RAW 264.7 cells. Results : 1. Compared with control, expressions of lipopolysaccharide-induced phospholipase $A_2$ were decreased significantly by $1\;{\mu}g/{\mu}l$ of bee venom and decreased by 0.5, $5\;{\mu}g/{\mu}l$ of bee venom. 2. Compared with control, expressions of sodium nitroprusside-induced phospholipase $A_2$ were decreased significantly by $5\;{\mu}g/{\mu}l$ of bee venom but increased by 0.5, $5\;{\mu}g/{\mu}l$ of bee venom. 3. Compared with control, expressions of hydrogen peroxide-induced phospholipase $A_2$ were decreased significaltly by $1{\mu}g/{\mu}l$ of bee venom and decreased by $0.5\;{\mu}g/{\mu}l$ of bee venom but increased by $5\;{\mu}g/{\mu}l$ of bee venom. 4. Compared with control, lipopolysaccharide, sodium nitroprusside and hydrogen peroxide- induced intracellular calcium concentrations were decreased by 0.5, 1, $5\;{\mu}g/{\mu}l$ of bee venom and by indomethacin

• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.77-90
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• 2003

The purpose of this study was to investigate the effect of Bee Venom on the lipopolysaccharide(LPS), sodium nitroprusside(SNP), hydrogen peroxide($H_2O_2$)-induced expressions of cyclooxygenase-2(COX-2), p38, jun N-terminal Kinase(JNK) and extra-signal response kinase(ERK) in RAW 264.7 cells, a murine macrophage cell line. Method : The expressions of COX-2, p38, JNK and ERK were determined by western blotting with corresponding antibodies. Results : 1. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly LPS and SNP-induced expression of COX-2 compared with control, respectively. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited insignificantly $H_2O_2$-induced expression of COX-2 compared with control, respectively. 2. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly LPS, SNP and $H_2O_2$-induced expression of p38 compared with control, respectively. 3. The 1 and $5\;{\mu}g/ml$ of bee venom inhibited significantly SNP-induced expression of JNK compared with control, respectively. All of bee venom inhibited insignificantly LPS and $H_2O_2$-induced expression of JNK compared with control, respectively. 4. The $5\;{\mu}g/ml$ of bee venom inhibited significantly SNP-induced expression of ERK, the $0.5\;{\mu}g/ml$ of bee venom increased significantly $H_2O_2$-induced expression of ERK compared with control. The 0.5, 1 and $5\;{\mu}g/ml$ of bee venom inhibited insignificantly LPS-induced expression of ERK compared with control, respectively.