• Journal of Acupuncture Research
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• v.19 no.5
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• pp.57-72
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• 2002

Objectives : This study was undertaken to determine the cytotoxic effects of crude bee venom which is widely used for aqua-acupuncture in oriental medical clinic. Methods : We compared the effects of crude bee venom, apamin, melittin and MCD peptide on cellviability by MTT asssay. Results : The obtained results are summarized as follows: 1. Bee venom, apamin, melittin and MCD peptide showed concentration--dependent cytotoxic effect in some human cell lines(human glioma cell line과 neuroblastorna, human mast cell line) for 24 and 48 Hour treatment. 2. Bee venom, apamin, melittin and MCD peptide showed dose-dependent cytotoxic effect in some human cell lines for 24 and 48 Hour treatment. 3. Bee venom treatment for 24 and 48 hour showed higher cytotoxic effects than apamin, melittin and MCD peptide. Conclusions : These results suggest that bee venom, apamin, melittin and MCD peptide have concentration- and dose- dependent cytotoxic effect in some human cell lines. But further study is needed for optimal concentration and dose.

• 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 Acupuncture Research
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• v.22 no.3
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• pp.37-51
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• 2005

Mast cell is a cell that functions mainly in our body with a respect to inflammation and allergic response. Bee venom has been progressed in a study as a model related to mechanism in alleviation of pain until now, but it is being progressed in a study relevant to immunocyte in anti-inflammation or anti-allergic response. The present study is aimed to present the basis related to a future study of gene, by researching the influence of melittin and MCD Peptide, which are major ingredients in Bee venom, upon the expression of gene in the mast cell strain. In this study, it dealt with melittin and MCD Peptide respectively, in the effective concentration after passing though the experiment of cytotoxicity by using human mast cell strain. Also, with the respect in the aspect of expression in gene that changes at this time, information was obtained through the technique of analyzing microarray. Through experimental statistics, when regarding a case that global M is significant in more than 1 or -1, in melittin, all 7 genes were accelerated, and 8 inhibited. In MCDP, 7 genes were accelerated and 17 genes inhibited. The function in the body to which these genes are related, was associated with the protein binding within a cell, the activation in the function of lymphocyte, the acceptor related to macrophage antigen. In cell nucleus, substance related to GABA A receptor, protein associated with cAMP reactive element, substance related to complement system No.8 and to B-cell, protein substance related to polycystic kidney disease, substance related to inflammation, and the protein substance of influencing coagulation of blood. Through these results of analysis, it could obtain more useful materials in clarifying the mechanism of action in melittin and MCD peptide, which are in charge of mainly medical action in the abdomen. Also, it is thought that an in-depth study on the influence of main ingredients in Bee venom, the wholly honey bee venom aqua upon anti-allergic response or anti-inflammation are further required.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.65-77
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• 2002

Objective : This study was undertaken to determine which compound of Bee Venom for herb-acupuncture has cytotoxicity on mouse mast cell line. Methods : We compared crude bee venom and its compounds such as melittin, mast cell degranulating peptide (MCD peptide), apamin with control groups on cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results & Conclusion : 1. Crude bee venom showed significant cytotoxic effect(p<0.01) in 1 hour treatment with $1{\mu}g/m{\ell}$ in comparison with control group in 1 hour treatment with low concentration of $10-4{\mu}g/m{\ell}$, $10-3{\mu}g/m{\ell}$, $10-2{\mu}g/m{\ell}$, $10-1{\mu}g/m{\ell}$ and $1{\mu}g/m{\ell}$, but it showed no significant cytotoxic effect in 6 hours treatment. 2. Melittin group showed no significant cytotoxic effect in comparison with control group in 1 and 6 hours treatment with low concentration of $10-4{\mu}g/m{\ell}$, $10-3{\mu}g/m{\ell}$, $10-2{\mu}g/m{\ell}$, $10-1{\mu}g/m{\ell}$ and $1{\mu}g/m{\ell}$. 3. MCD peptide and Apamin group showed no significant cytotoxic effect in comparison with control group in 1 and 6 hours treatment with low concentration of $10-4{\mu}g/m{\ell}$ $10-3{\mu}g/m{\ell}$, $10-2{\mu}g/m{\ell}$, $10-1{\mu}g/m{\ell}$ and $1{\mu}g/m{\ell}$. 4. Crude bee venom showed significant cytotoxic effect(p<0.01) in 1 and 6 hours treatment in comparison with control group in 1 and 6 hours treatment with high concentration of $10{\mu}g/m{\ell}$, $20{\mu}g/m{\ell}$ and $102{\mu}g/m{\ell}$. 5. Melittin group showed significant cytotoxic effect(p<0.01) in 1 hour treatment in comparison with control group in 1 hour treatment with high concentration of $10{\mu}g/m{\ell}$ but it showed no significant cytotoxic effect in 6 hours treatment. 6. Crude bee venom and its compounds have more cytotoxic effect in 1 hour treatment than in 6 hours treatment. It means cytotoxicity tends to decrease according to the treatment time.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.151.2-152
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• 2003

Bee venom (BV) has been utilized to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). BV contains a variety of different peptides including melittin, apamin, adolapin and mast cell degranulating (MCD) peptide. In addition, it also contains enzyme (i.e. phospholipase A2), biologically active amines and non-peptide components. (omitted)

• Journal of Acupuncture Research
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• v.17 no.4
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• pp.149-159
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• 2000

Bee-venom Acupucture has good effect on pain control but We may be anxious about the problem of side-effect. Bee-venom components are composed of phospholipase $A_2$, hyaluronidase, melitin, apamin, MCD peptide, citrate and so on. Especially Apamin, MCD peptide and histamine cause severe reacting that is named Anaphylaxis. Anaphylaxis is a clinical syndrome characterized by the acute system reaction of multiple organ systems to an IgE-mediated immunologic mediator release in previously sensitized individuals. Respiratory and dermatologic manifestations are the most commonly expressed clinical features of anaphylaxis, and a majority of anaphylactic reactions initially appear to be localized to these two systems. Anaphylatic reaction of bee-venom are expressed clinically ulticaria, itching sensation, erythema, dizziness, nausea, hypotension and so on. Especially ulticaria and erythema are end points of increased vascular permeability and vasodilatation at the other extreme of the clinical spectrum, Gastrointestinal mucosal edema and smooth muscle contraction can result in cramping abdominal pain, nausea, and vomiting. Therefore, we have observed anaphylatic reaction of bee-venom in 11 patients, who visited WonKwang University Kunpo Oriental Medical Center, treated bee venom. The results were summarized as follows : 1. The patient distribution ratio, in regard to sex, was shown to be 1 : 2.67 for male to females. In regard to age, it was shown that people in their 30's was the most predominant case, followed by people in their 20's, 30's, 50's and 60's, respectively. 2. When Anaphylaxis was occured, it was observed to abnormality of CBC, LFT, IgE, IgG. 3. In regard to patient condition, it was observed that fatigue was most frequent. 4. In regard to the number of times and quantity of bee venom inj., it was observed that anaphylaxis is most frequent at 7-10 times(1.6-2.0cc) 5. In regard to duration of reaction, it was observed that people in their l0min' was most frequent. In disappearing duration of anaphylaxic reaction, The results showed under 60min lcases(9%), 60-120min 7cases(64%) and 180-240min 3cases(27%). 6. In symptoms of anaphylaxis, The results showed hypotension 8cases(19%), itching sensation 7cases(16%), nausea 4cases(9%), erythema 4cases(9%) and dizziness 4cases(9%). In mentality, The results showed drowsy 8case(73%) and alert 3cases(27%). 7. Generally, patients were treated with Avil, Dexa IM and PDS, peniramine, cimetidine, Q-zyme per os after H/S, N/S inj. $O_2$ was supplied according to patient's symptom. In 1 severe case, Dopamine was iv injected.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.92-98
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• 2013

Bee Venom(below BV) has been used in alternative medicine to treat the diseases, such as pain diseases. BV contains a variety of peptides, including melittin, apamin, adolapin, MCD peptide, enzymes(i.e. PLA2), amines(i.e. histamine and epinephrine), and nonpeptide components. The two main components of BV are melittin and PLA2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the depress of cancer cell. Melittin and PLA2 have been reported to induce apoptosis and to possess anti-cancer effects and neurite outgrowth in PC12 cells. Analysis of proliferation was confirmed by MTT assay. BV decreased cell number through dose- and duration-dependent manner and these effects are apparent at a concentration of 3 ${\mu}g/ml$. To observe which signaling molecules will be activated by BV, phosphorylation of ERK, p38 MAPK, JNK and ERM were examined by Western blot analysis. To study the long term effect of BV in human gastric adenocarcinoma cell lines, the image of cells treated with BV for 4 days were obtained. BV was shown to exhibit anti-cancer activity in human gastric adenocarcinoma cell lines at a broad range of concentrations of 3 ${\mu}g/ml$. ERK, p38 MAPK and JNK were found to increase in BV treated cells. However, ERM which known to be involved in the cell death, was gradually decreased to 30minutes after addition 3 ${\mu}g/ml$ of BV. These results provide a possible BV-induced inhibitory signal for cancer proliferation that is initiated by the decrease in ERM activity. Moreover, it is likely that the activation of ERK, p38 MAPK and JNK are required for the BV-induced inhibition of cancer proliferation.

• 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 Acupuncture Research
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• v.20 no.4
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• pp.53-65
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• 2003

Although the effect of Bee Venom has been reported, its mechanism has not been fully elucidated. Nitric Oxide(NO) is one of the free radicals and mediates in inflammation diseases. Chemokines contribute to the pathogenesis of several disorders such as allergic rhinitis and rheumatoid arthritis and so on. The objective of this study was to investigate the scavenging effect of Bee Venom on NO and on expression of chemokine genes. There was no significant NO scavenging effect in Crude Bee Venom, Apamin, Melittin, and MCD-peptide. The expression of chemokines was examined by RT-PCR using the human mast cell line(HMC-1), which is known to secrete and express chemokines. In order to investigate the protective effect of Bee Venom, HMC-1 cells were incubated with pretreatment of Bee Venom for 24 hrs and stimulated with 1 uM calcium ionophore A23178 for 2 hrs. RT-PCR analyses of chemokine genes showed that expressions of RANTES and MCP-1 were increased compared to the calcium ionophore-only treated group. But IL-8 and MCP-3 did not express increasing effect compared to control group. This study may provide important basic data on the possibility of the clinical treatment of Bee Venom in inflammation diseases.