• The Journal of Korea CHUNA Manual Medicine
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• v.3 no.1
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• pp.111-123
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• 2002

Objectives : There have been many studies of the effect of Bee Venom therapy about arthritis, but no one study was reported about its whole functional mechanism to musculo-skeletal system. This study was designed to investigate the effect, Indication, and side effect of Bee Venom therapy on musculo-skeletal disease by literature review of articles. Results : The effects of Bee Venom therapy to musculo-skeletal system are divided to Anti_inflammatory effect and Anti-nociceptive effect. Anti_inflammatory effect is achieved through competitive chemotaxis, immuno-regulation, increasing of cortisol secretion by stimulating hypothalamus-pituitary gland-adrenal cortex axis. Anti-nociceptive effect is achieved by Anti-inflammatory mechanism and it works similar to anti-nociceptive effect of the acupuncture acting on central and peripheral nociceptive transduction system. The Bee Venom therapy could cause severe side effect, for example, hypersensitivity and anaphylaxis, injury to central nerve system and cardiovascular system, peripheral blood system, and renal dysfunction. Conclusions : With its Anti-inflammatory and Anti-nociceptive mechanism, Bee Venom therapy is considered that has good effects to autoimmune disease, chronic inflammation of various musculo-skeletal disease and various pain syndrome. But the clinician must be careful for its side effects.

• Journal of Pharmacopuncture
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• v.4 no.2
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• pp.5-15
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• 2001

This study was carried out for production of neutral antibody to bee venom $(anti-phospholipase\;A_2IgY)$. Hen layings were injected repeatedly with bee venom and phospholipase $A_2$ with Freund's adjuvant. Specific antibody in egg yolk from immunized hen laying was separated, and purified, also immunological characteristics of anti phospholipase $A_2\;IgY$ was invested. The results were summarized as follows: 1. Phospholipase $A_2$ was showed single band at molecular weight 17,000 in SDS-PAGE and bee venom was showed two band at molecular weight 17,000 and under molecular weight 6,500 in SDS-PAGE. 2. During 70 days after hen immunized with bee venom and phospholipase $A_2$, antibodies(anti-bee venom IgY) to bee venom were showed poor ELISA value in egg yolk, but antibodies$(anti-Phospholipase\;A_2IgY)$ to phospholipase $A_2$ in egg yolk were increased ELISA value from 8 days or 15 days and found maximum ELISA value at 42 days. Also after booster at 49 days, ELISA value of anti Phospholipase $A_2\;IgY$ in egg yolk was supported at optical density(O.D) 1.0 level, continuously. 3. Titer of phospholipase $A_2\;IgY$ was showed 1: 32,000. 4. In double immunodiffusion test to phospholipase $A_2$ after double dilution of anti-phospholipase $A_2\;IgY$, only precipitation line was made in 1:1 dilution well of anti-Phospholipase $A_2\;IgY$. But In immunodiffusion test to anti-phospholipase $A_2\;IgY$ after double dilution of phospholipase $A_2$, Precipitation line to 250ul/ml well of phospholipase $A_2$ was showed. In double immunodiffusion test to bee venom(1mg/ml) after double dilution anti-phospholipase $A_2\;IgY$, all well without 1:32 dilution well were showed strong precipitation line. 5. In dot bloting test to anti-phospholipase $A_2\;IgY$ after diluting bee venom(0.5mg/ml), dot bloting color was showed clearly to $1/100(5{\mu}g/ml)$ in bee venom.

• Journal of Acupuncture Research
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• v.22 no.6
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• pp.37-50
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• 2005

Objectives : The purpose of this study was to investigate the anti-caner effect of Bee Venom and Melittin on the prostatic cancer cell(PC-3). The goal of study is to ascertain whether Bee Venom and Melittin inhibits the cell growth and cell cycle of PC-3, or the expression of relative genes and whether the regression of PC-3 cell growth is due to cell death or the expression of gene related to apoptosis. Methods : After the treatment of Pc-3 cells with Bee Venom and Melittin, we performed Fluorescence microscope, MTT assay, Western blotting, Flow cytometry, PAGE electrophoresis and Surface plasmon resonance analysis to identify the cell viability, apoptosis and gene related to apoptosis. Results : 1. Compared with Control cell, the inhibition of cell growth reduced in proportion with the dose of Bee Venom or Melittin($0{\sim}10{\mu}g/ml$) in PC-3. 2. In PC-3, Cell viabilities of Bee Venom or Melittin treatment was decreased significantly. 3. The nucli of Control cells were stained round and homogenous in DAPI staining, but those of PC-3 were stained condense and splitted. 4. In PC-3, apoptosis of Bee Venom or Melittin treatment was increased significantly. 5. Bax, Caspase-3 and P ARP of Bee Venom or Melittin treatment was increased significantly and Bcl-2 of Bee Venom or Melittin treatment was decreased significantly. Caspase-9 of Bee venom treatment was increased significantly. Conclusion : These results indicate that Bee Venom and Melittin inhibits the growth of prostate cancer cells, has anti-cancer effects by inducing apoptosis. We wish that the anti-cancer effects of Bee Venom and Melittin are used to clinical caner treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.167-173
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• 2005

To investigate the possible molecular mechanism (s) of bee venom as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Bee venom treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Bee venom down-regulated the levels of anti-apoptotic genes such as Bcl-2 and Bcl-XS/L, however, the levels of Bax, a pro-apoptotic gene, were up-regulated. Bee venom treatment induced not only tumor suppressor p53 but also cyclin-dependent kinase inhibitor p21WAF1/CIP1 expression in a dose-dependent manner. Furthermore, bee venom treatment induced the down-regulation of telomerase reverse transcriptase mRNA and telomeric repeat binding factor expression of A549 cells, however, the levels of telomerase-associated protein-1 and c-myc were not affected. Taken together, these findings suggest that bee venom-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and bee venom may have therapeutic potential in human lung cancer.

• Journal of Acupuncture Research
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• v.15 no.2
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• pp.97-103
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• 1998

Purpose: In order to study the anti-inflammatory and analgesic effects of Bee Venom Therapy, writhing syndrome, carrageenin induced edema, and complete adjuvant induced arthritis were experimented. Methods: 1. We used rats of writhing syndrom induced by acetic acid injection. Group I was treated with Acupuncture therapy. Group II was treated with Bee Venom thearpy. we compared with Group I, II and the control group. 2. We used rats of paw edema induced by carrageenin injection. Group I Was treated with Acupuncture therapy, Group II was treated with Bee Venom thearpy we compared with Group I, II and the control group. 3. We used rats of arthritis induced by Freud's complete adjuvant injection. Group I was treated with Acupuncture therapy, Group II was treated with Bee Venom thearpy we compared with GroupI,II and the control group. Results: 1. Analgesic effects on writhing syndrome induced by acetic acid injection showed statistical significance in Bee Venom treated group as compared with the control group. 2. The paw edema induced by carrageenin injection was decreased with statistical significance in Bee Venom treated group as compared with the control group. 3. The arthritis induced by Freud's complete adjuvant injection wasn't significant. Conclusion: Bee Venom Therapy was effective on inflammatory disease.

• 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 Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.132-137
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• 2011

Bee venom acupuncture (BVA), as a kind of herbal acupuncture, involved injecting diluted bee venom into acupoints and is used for pain, osteoarthritis and rheumatoid arthritis patients. BVA is growing in popularity, especially in Korea, and is used primarily for pain relief in many kinds of diseases. However, the effect of bee venom anti-inflammatory related action in lipopolysaccharide (LPS) induced chondrocyte stress have not been reported yet. The aim of this study was to investigate the effect of bee venom of cell viability and inflammatory cytokine in rat articular chondrocyte cultures stimulated with lipopolysaccharide. Inflammation was induced in rat chondrocytes by treatment with $10{\mu}g/m{\ell}$ LPS. The change of cell viability were decreased in chondrocytes after treatment with lipopolysaccharide. The cell viability revealed that BV exerted no significant cytotoxicity in the rat chondrocyte. Bee venom inhibited decreased cell viability in the presence of lipopolysaccharide ($10{\mu}g/m{\ell}$) in a dose dependent manner(0.1, 0.5, 1.0 and $5.0{\mu}g/m{\ell}$) at bee venom(p<0.05). Tumor necrosis factor (TNF)-${\alpha}$ production in the presence of lipopolysaccharide($1{\mu}g/m{\ell}$) was also inhibited in a dose dependent manner (p<0.05 from bee venom $0.1{\mu}g/m{\ell}$). Interleukin (IL)-6 production in the presence of lipopolysaccharide ($10{\mu}g/m{\ell}$) was inhibited as well (p<0.05 at bee venom 0.1, 0.5, 1.0 and $5.0{\mu}g/m{\ell}$, respectively). Our results demonstrate that bee venom was a anti-inflammatory agent of chondrocytes. Bee venom may exert its anti inflammatory effects through inhibition of TNF-${\alpha}$ and IL-6 synthesis, and may then pain relief and reduce the articular destruction.

• Journal of Haehwa Medicine
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• v.15 no.1
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• pp.141-160
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• 2006

The obtained results are summarized as follows 1. New findings are reporting year by year as for the study related to Anti-inflammatory mechanism of Bee Venom therapy. 2. The Anti-inflammatory effect of Bee Venom therapy is achieved through counterirritation, stimulations to adrenal cortex, immuno-regulation, antioxidation, removal of free radicals, modulation of AGP gene induction. 3. The chief components of Bee Venom related to Anti-inflammatory effect are Melittin, MCD peptide, Apamin, Adolapin etc. 4. Melittin binds to secretory phospholipase A2 and inhibits its enzymatic activity. 5. Melittin blocks neutophil O2-production. 6. MCD peptide(Peptide 401) stimulates the mast cell secrets histamine, Anti-inflammatory effect caused by this is 'conterirritation'. 7. Melittin & Apamin have an anti-inflammatory effect by inducing cortisone secretion. 8. MCD peptide & Apamin increase immunologic fuction by stimulating hypophysis & adrenal cortex and have an anti-inflammatory effect by inhibiting synthesis of prostaglandin from arachidonic acid. 9. Adolapin have an anti-inflammatory effect by inhibiting COX. 10. Bee Venom have an anti-inflammatory effect by suppressing AGP($\alpha$-acid glycoprotein). 11. Bee Venom have an anti-inflammatory effect by inhibiting NO, iNOS, PLA2, COX-2, TNF-$\alpha$, IL-1, NF-${\kappa}B$, MAP kinase.

• Journal of Pharmacopuncture
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• v.3 no.1
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• pp.1-19
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• 2000

To study anti-cancer effect and molecular biological mechanism of bee venom for aqua-acupuncture, the effects of bee venom on cell viability and apoptosis were analyzed using MTT assay, tryphan blue assay, $[^3H]$thymidine release assay, flow cytometric analysis, and activity of caspase-3 protease activity assay. To explore whether anti-cancer effects of bee venom are associated with the transcriptional control of gene expression, quantitative RT-PCR analysis of apoptosis-related genes was performed. The obtained results are summarized as follows: 1. The MTT assay demonstrated that cell viability was decreased by bee venom in a dose-dependant manner. 2. Significant induction of apoptosis was identified using tryphan blue assay, $[^3H]$thymidine release assay, and flow cytomet1 ric analysis of sub $G_1$ fraction. 3. In analysis of caspase-3 protease activity, the activity had increased significantly, in a dose-dependant manner. 4. Quantitative RT-PCR analysis of the apoptosis-related genes showed that Bcl-2 and Bcl-$X_L$ were down-regulated whereas Bax was up-regulated by bee venom treatment.

• Journal of Pharmacopuncture
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• v.9 no.2
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• pp.79-86
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• 2006

Objectives : The aim of this study was to observe prevention of allergic reactions of Sweet Bee Venom (removing enzyme components from Bee Venom). Methods: Content analysis of Sweet Bee Venom and Bee Venom was rendered using HPLC method and characterization of Anti-Sweet Bee Venom in Rabbit Serum. Clinical observation was conducted for inducement of allergic responses to Sweet BV. Results : 1. Analyzing melittin content using HPLC, Sweet BV contained 34.9% more melittin than Bee venom pharmacopuncture at same concentration. 2. Observing chromatogram of HPLC, removal of the enzyme was successfully rendered on Sweet BV. 3. The anti-serum of Sweet BV showed high titers against melittin and bee venom and relatively low titer against phospholipase A2. 4. After conducting approximately 3,000 cases of Sweet BV administration, not a single case of generalized anaphylatic reaction occurred in clinical observation. 5. Mild compared to the bee venom pharmacopuncture, Sweet BV showed some acute hypersensitive reactions of edema, itchiness, and aching locally. 6. Sweet BV was administered on six patients with previous history of suffering from generalized acute hypersensitive reactions with the bee venom. None of the patients showed allergic reactions with Sweet BV, suggesting it can effectively prevent anaphylatic shock which may occur after the bee venom pharmacopuncture procedure. Conclusion : Summarizing above results, Sweet Bee Venom appears to be an effective measurement against allergic reactions from the bee venom pharmacopuncture especially against anaphylatic shock.